insulin--isophane and Diabetes-Mellitus--Type-2

To investigate the effectiveness, safety, optimal starting dose, optimal maintenance dose range, and target fasting plasma glucose of five basal insulins in insulin-naïve patients with type 2 diabetes mellitus.. MEDLINE, EMBASE, Web of Science, and the Cochrane Library were searched from January 2000 to February 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was adopted. The registration ID is CRD42022319078 in PROSPERO.. Among 11 163 citations retrieved, 35 publications met the planned criteria. From meta-analyses and network meta-analyses, we found that when injecting basal insulin regimens at bedtime, the optimal choice in order of most to least effective might be glargine U-300 or degludec U-100, glargine U-100 or detemir, followed by neutral protamine hagedorn (NPH). Injecting glargine U-100 in the morning may be more effective (ie, more patients archiving glycated hemoglobin < 7.0%) and lead to fewer hypoglycemic events than injecting it at bedtime. The optimal starting dose for the initiation of any basal insulins can be 0.10-0.20 U/kg/day. There is no eligible evidence to investigate the optimal maintenance dose for basal insulins.. The five basal insulins are effective for the target population. Glargine U-300, degludec U-100, glargine U-100, and detemir lead to fewer hypoglycemic events than NPH without compromising glycemic control.

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

NO. Insulin glargine may lead to less patient-reported, symptomatic, and nocturnal hypoglycemia, although overall, there may not be a difference in the risk for severe hypoglycemia orhypoglycemiarelated emergency department (ED) visits and hospitalizations (strength of recommendation [SOR]: B, systematic review of randomized controlled trials [RCTs], individual RCTs, and observational study).

Topics: Adult; Aged; Aged, 80 and over; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Insulin Glargine; Insulin, Isophane; Male; Middle Aged; Treatment Outcome

Evidence that antihyperglycaemic therapy is beneficial for people with type 2 diabetes mellitus is conflicting. While the United Kingdom Prospective Diabetes Study (UKPDS) found tighter glycaemic control to be positive, other studies, such as the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, found the effects of an intensive therapy to lower blood glucose to near normal levels to be more harmful than beneficial. Study results also showed different effects for different antihyperglycaemic drugs, regardless of the achieved blood glucose levels. In consequence, firm conclusions on the effect of interventions on patient-relevant outcomes cannot be drawn from the effect of these interventions on blood glucose concentration alone. In theory, the use of newer insulin analogues may result in fewer macrovascular and microvascular events.. To compare the effects of long-term treatment with (ultra-)long-acting insulin analogues (insulin glargine U100 and U300, insulin detemir and insulin degludec) with NPH (neutral protamine Hagedorn) insulin (human isophane insulin) in adults with type 2 diabetes mellitus.. For this Cochrane Review update, we searched CENTRAL, MEDLINE, Embase, ICTRP Search Portal and ClinicalTrials.gov. The date of the last search was 5 November 2019, except Embase which was last searched 26 January 2017. We applied no language restrictions.. We included randomised controlled trials (RCTs) comparing the effects of treatment with (ultra-)long-acting insulin analogues to NPH in adults with type 2 diabetes mellitus.. Two review authors independently selected trials, assessed risk of bias, extracted data and evaluated the overall certainty of the evidence using GRADE. Trials were pooled using random-effects meta-analyses.. We identified 24 RCTs. Of these, 16 trials compared insulin glargine to NPH insulin and eight trials compared insulin detemir to NPH insulin. In these trials, 3419 people with type 2 diabetes mellitus were randomised to insulin glargine and 1321 people to insulin detemir. The duration of the included trials ranged from 24 weeks to five years. For studies, comparing insulin glargine to NPH insulin, target values ranged from 4.0 mmol/L to 7.8 mmol/L (72 mg/dL to 140 mg/dL) for fasting blood glucose (FBG), from 4.4 mmol/L to 6.6 mmol/L (80 mg/dL to 120 mg/dL) for nocturnal blood glucose and less than 10 mmol/L (180 mg/dL) for postprandial blood glucose, when applicable. Blood glucose and glycosylated haemoglobin A1c (HbA1c) target values for studies comparing insulin detemir to NPH insulin ranged from 4.0 mmol/L to 7.0 mmol/L (72 mg/dL to 126 mg/dL) for FBG, less than 6.7 mmol/L (120 mg/dL) to less than 10 mmol/L (180 mg/dL) for postprandial blood glucose, 4.0 mmol/L to 7.0 mmol/L (72 mg/dL to 126 mg/dL) for nocturnal blood glucose and 5.8% to less than 6.4% HbA1c, when applicable. All trials had an unclear or high risk of bias for several risk of bias domains. Overall, insulin glargine and insulin detemir resulted in fewer participants experiencing hypoglycaemia when compared with NPH insulin. Changes in HbA1c were comparable for long-acting insulin analogues and NPH insulin. Insulin glargine compared to NPH insulin had a risk ratio (RR) for severe hypoglycaemia of 0.68 (95% confidence interval (CI) 0.46 to 1.01; P = 0.06; absolute risk reduction (ARR) -1.2%, 95% CI -2.0 to 0; 14 trials, 6164 participants; very low-certainty evidence). The RR for serious hypoglycaemia was 0.75 (95% CI 0.52 to 1.09; P = 0.13; ARR -0.7%, 95% CI -1.3 to 0.2; 10 trials, 4685 participants; low-certainty evidence). Treatment with insulin glargine reduced the incidence of confirmed hypoglycaemia and confirmed nocturnal hypoglycaemia. Treatment with insulin detemir compared to NPH insulin found an RR for severe hypoglycaemia of 0.45 (95% CI 0.17 to 1.20; P = 0.11; ARR -0.9%, 95% CI -1.4 to 0.4; 5 trials, 1804 participants; very low-certainty evidence). The Peto odds ratio for serious hypoglycaemia was 0.16, 95% CI 0.04 to 0.61; P = 0.007; ARR -0.9%, 95% CI -1.1 to -0.4; 5 trials, 1777 participants; low-certainty evidence). Treatment with detemir also reduced the incidence of confirmed hypoglycaemia and confirmed nocturnal hypoglycaemia. Information on patient-relevant outcomes such. While the effects on HbA1c were comparable, treatment with insulin glargine and insulin detemir resulted in fewer participants experiencing hypoglycaemia when compared with NPH insulin. Treatment with insulin detemir also reduced the incidence of serious hypoglycaemia. However, serious hypoglycaemic events were rare and the absolute risk reducing effect was low. Approximately one in 100 people treated with insulin detemir instead of NPH insulin benefited. In the studies, low blood glucose and HbA1c targets, corresponding to near normal or even non-diabetic blood glucose levels, were set. Therefore, results from the studies are only applicable to people in whom such low blood glucose concentrations are targeted. However, current guidelines recommend less-intensive blood glucose lowering for most people with type 2 diabetes in daily practice (e.g. people with cardiovascular diseases, a long history of type 2 diabetes, who are susceptible to hypoglycaemia or older people). Additionally, low-certainty evidence and trial designs that did not conform with current clinical practice meant it remains unclear if the same effects will be observed in daily clinical practice. Most trials did not report patient-relevant outcomes.

Topics: Bias; Diabetes Mellitus, Type 2; Hemoglobin A; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Randomized Controlled Trials as Topic

Insulin allergy is a rare yet severe side effect of exogenous insulin use. Management typically involves use of alternative antihyperglycaemic agents, symptom control with antihistamines, use of different insulin formulations, and induction of tolerance with incremental doses of insulin. This treatment regimen is not always successful, and the use of omalizumab, an anti-IgE monoclonal antibody, has been used to induce tolerance to insulin.. G.M. is a 62-year-old man with Type 2 diabetes mellitus. His condition was not optimized on oral agents, and insulin therapy was required. G.M. had anaphylaxis to insulin NPH, and subsequent skin-prick testing was positive to insulin aspart, insulin NPH, insulin glulisine, insulin detemir, regular insulin, insulin glargine 100 units/ml and insulin glargine 300 units/ml. He received incremental doses of several insulin formulations; however, he experienced diffuse urticaria preventing optimal glycaemic control. Three successful cases have been described in the literature of omalizumab inducing tolerance to exogenous insulin; therefore, G.M. was started on omalizumab. He subsequently tolerated treatment doses of insulin glulisine and insulin detemir with no allergic reactions and with improvement in glycaemic control.. To our knowledge, this is the first described case of allergy to insulin glargine 300 units/ml and reiterates the potential use of omalizumab in insulin allergy. Further research is warranted to determine if omalizumab should be considered standard of care in difficult-to-treat insulin hypersensitivity.

Topics: Anaphylaxis; Anti-Allergic Agents; Diabetes Mellitus, Type 2; Drug Hypersensitivity; Humans; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Male; Middle Aged; Omalizumab

Since clinical experience with biphasic insulin aspart 30 (BIAsp 30) in type 2 diabetes mellitus (T2DM) was reviewed in 2012 after 10 years of use worldwide, additional studies have been published that highlight new aspects, including use in real-world populations. Evidence from 35 new studies confirms and builds upon previous work indicating that BIAsp 30 continues to have pharmacodynamic and clinical advantages over biphasic human insulin (BHI 30), including in real-world practice with unselected populations of patients. BIAsp 30 has also been shown to be safe and efficacious as an add-on to dipeptidyl peptidase-4 (DPP-4) inhibitors. Intensification with BIAsp 30 is a safe and effective way to improve glycemic control, and titration performed by patients can achieve results that are at least comparable to those when being guided by healthcare providers. Stepwise intensification using BIAsp 30 is comparable to intensification using a basal-bolus regimen, and twice-daily BIAsp 30 provides similar glycemic control to a basal-plus regimen. Data from large observational studies, in particular, have identified patient-related characteristics that are associated with improved clinical responses, suggesting that earlier initiation and intensification of therapy is warranted. Finally, new health-economic analyses continue to confirm that BIAsp 30 is cost effective versus other therapies such as BHI 30, neutral protamine Hagedorn (NPH), or insulin glargine in both insulin-naïve and insulin-experienced patients. After 15 years of clinical use worldwide, analysis of more recent 5-year data indicates that BIAsp 30 remains a safe, effective, and simple-to-use insulin for initiation and intensification by diabetes specialists and primary care physicians in a variety of patients with T2DM.

Topics: Biphasic Insulins; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane

Evaluate efficacy and hypoglycaemia according to concomitant oral antidiabetes drug (OAD) in people with type 2 diabetes initiating insulin glargine 100U/mL (Gla-100) or neutral protamine Hagedorn (NPH) insulin once daily.. Four studies (target fasting plasma glucose [FPG] ⩽100mg/dL [⩽5.6mmol/L]; duration ⩾24weeks) were included. Standardised data from 2091 subjects (Gla-100, n=1024; NPH insulin, n=1067) were analysed. Endpoints included glycated haemoglobin (HbA1c) and FPG change, glycaemic target achievement, hypoglycaemia, weight change, and insulin dose.. Mean HbA1c and FPG reductions were similar with Gla-100 and NPH insulin regardless of concomitant OAD (P=0.184 and P=0.553, respectively) and similar proportions of subjects achieved HbA1c <7.0% (P=0.603). There was a trend for more subjects treated with Gla-100 achieving FPG ⩽100mg/dL versus NPH insulin (relative risk [RR] 1.09 [95% confidence interval (CI) 0.97-1.23]; P=0.135). Plasma glucose confirmed (<70mg/dL) overall and nocturnal hypoglycaemia incidences and rates were lower with Gla-100 versus NPH insulin (overall RR 0.93 [95% CI 0.87-1.00]; P=0.041; nocturnal RR 0.73 [95% CI 0.65-0.83]; P<0.001). After 24weeks, weight gain and insulin doses were higher with Gla-100 versus NPH insulin (2.7kg vs 2.3kg, P=0.009 and 0.42U/kg vs 0.39U/kg; P=0.003, respectively). Insulin doses were higher when either insulin was added to sulfonylurea alone.. Pooled results from treat-to-target trials in insulin-naïve people with type 2 diabetes demonstrate a significantly lower overall and nocturnal hypoglycaemia risk across different plasma glucose definitions with Gla-100 versus NPH insulin at similar glycaemic control. OAD therapy co-administered with Gla-100 or NPH insulin impacts glycaemic control and overall nocturnal hypoglycaemia risk.

Topics: Administration, Oral; Clinical Trials, Phase III as Topic; Clinical Trials, Phase IV as Topic; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Glargine; Insulin, Isophane; Male; Randomized Controlled Trials as Topic; Sulfonylurea Compounds; Treatment Outcome; Weight Gain

The goal of this post hoc analysis was to determine key patient and treatment-related factors impacting glycosylated hemoglobin (A1C) and hypoglycemia in patients with uncontrolled type 2 diabetes who were initiated to basal insulin (neutral protamine Hagedorn [NPH] or glargine).. Using individual patient-level data pooled from 6 treat-to-target trials, 2600 patients with type 2 diabetes on oral antidiabetic agents initiated to insulin glargine or NPH and treated for 24 to 36 weeks were analyzed.. Both treatments led to significant reduction in A1C levels compared with baseline, with no differences between treatment groups (mean ± standard deviation; glargine: -1.32 ± 1.2% vs NPH: -1.26 ± 1.2%; P = 0.15), with greater reduction in the BMI ≥30 kg/m group than in the BMI <30 kg/m group. Glargine reduced A1C significantly more than NPH in the BMI <30 kg/m group (-1.30 ± 1.18% vs -1.14 ± 1.22, respectively; P = 0.008), but not in the BMI ≥ 30 kg/m group (-1.37 ± 1.19 vs -1.48 ± 1.22, respectively; P = 0.18). Similar proportions of patients achieved A1C target of <7% (glargine 30.6%, NPH 29.1%; P = 0.39). Incidence of severe and severe nocturnal hypoglycemia was significantly lower in glargine versus NPH-treated patients (2.0% vs 3.9%; P = 0.04, and 0.7% vs 2.1%; P = 0.002, respectively), and occurred primarily in the BMI <30 kg/m group.. Initiation of basal insulin is highly effective in lowering A1C after oral antidiabetic agent failure. Glargine decreases A1C more than NPH in nonobese patients, and reduces the risk for severe and severe nocturnal hypoglycemia versus NPH both in obese and nonobese patients, but more so in nonobese patients. Thus, it is the nonobese patients who may benefit more from initiation of basal insulin as glargine than NPH.

Topics: Adult; Aged; Aged, 80 and over; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Male; Middle Aged; Obesity; Randomized Controlled Trials as Topic; Treatment Outcome; Young Adult

Basal insulin peglispro (BIL) is a novel basal insulin with a flat, prolonged activity profile. BIL has been demonstrated in a dog model, in healthy men and in patients with type 1 diabetes (T1D) to have significant hepato-preferential action resulting from reduced peripheral activity. In the IMAGINE-Phase 3 clinical trial program, more than 6000 patients were included, of whom ~3900 received BIL. Of the 7 pivotal IMAGINE trials, 3 studies were double-blinded and 3 were in T1D patients. BIL consistently demonstrated a greater HbA1c reduction, less glycaemic variability and a clinically relevant reduction in the rates of nocturnal hypoglycaemia across comparator [glargine and isophane insulin (NPH)] studies. Trials using basal/bolus regimens had higher rates of total hypoglycaemia with BIL due to higher rates of daytime hypoglycaemia. Severe hypoglycaemia rates were similar to comparator among both patients with T1D or type 2 diabetes (T2D). T1D patients lost weight compared with glargine (GL). Patients with T2D tended to gain less weight with BIL than with glargine. Compared to glargine, BIL was associated with higher liver fat, triglycerides and alanine aminotransferase (ALT) levels, including a higher frequency of elevation of ALT ≥3 times the upper limit of normal, but without severe, acute drug-induced liver injury. Injection site reactions, primarily lipohypertrophy, were more frequent with BIL. In conclusion, BIL demonstrated better glycaemic control with reduced glucose variability and nocturnal hypoglycaemia but higher triglycerides, ALT and liver fat relative to conventional comparator insulin. The hepato-preferential action of BIL with reduced peripheral activity may account for these findings.

Topics: Alanine Transaminase; Blood Glucose; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Isophane; Liver; Polyethylene Glycols; Treatment Outcome; Triglycerides; Weight Loss

A variety of basal insulin preparations are used to treat patients with type 2 diabetes mellitus (T2DM). We aimed to summarize scientific evidence on relative efficacy and safety of insulin glargine (IGlar) and other insulins in T2DM.. A systematic review was carried out in major medical databases up to December 2012. Relevant studies compared efficacy and safety of IGlar, added to oral drugs (OAD) or/and in combination with bolus insulin, with protamine insulin (NPH) or premixed insulin (MIX) in the same regimen, as well as with insulin detemir (IDet), in T2DM. Target HbA1c level without hypoglycemic events was considered the primary endpoint.. Twenty eight RCTs involving 12,669 T2DM patients followed for 12-52 weeks were included in quantitative analysis. IGlar + OAD use was associated with higher probability of reaching target HbA1c level without hypoglycemia as compared to NPH + OAD (RR = 1.32 [1.09, 1.59]) or MIX without OAD (RR = 1.61 [1.22, 2.13]) and similar effect as IDet + OAD (RR = 1.07 [0.87, 1.33]) and MIX + OAD (RR = 1.09 [0.86, 1.38]). IGlar + OAD demonstrated significantly lower risk of symptomatic hypoglycemia as compared to NPH + OAD (RR = 0.89 [0.83, 0.96]), MIX + OAD (RR = 0.75 [0.68, 0.83]) and MIX without OAD(RR = 0.75 [0.68, 0.83]), but not with IDet + OAD (RR = 0.99 [0.90, 1.08]). In basal-bolus regimens, IGlar demonstrated similar proportion of T2DM patients achieving target HbA1c as compared to NPH (RR = 1.14 [0.91, 1.44]) but higher than MIX (RR = 1.26 [1.12, 1.42) or IDet (RR = 1.38 [1.11, 1.72]). The risk of severe hypoglycemia was lower in IGlar than in NPH (RR = 0.77 [0.63, 0.94]), with no differences in comparison with MIX (RR = 0.74 [0.46, 1.20]) and IDet (RR = 1.10 [0.54, 2.25]). IGlar + OAD has comparable safety profile to NPH, with less frequent adverse events leading to treatment discontinuation than MIX + OAD (RR = 0.41 [0.22, 0.76]) and IDet + OAD (RR = 0.40 [0.24, 0.69]). Also severe adverse reactions were less common for IGlar + OAD when compared to MIX + OAD (RR = 0.71 [0.52; 0.98]).. For the majority of examined efficacy and safety outcomes, IGlar use in T2DM patients was superior or non-inferior to the alternative insulin treatment options.

Topics: Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Randomized Controlled Trials as Topic; Treatment Outcome

To determine the impact of gender on glycaemic control and hypoglycaemia in insulin-naïve patients with type 2 diabetes (T2DM).. Data were pooled from six randomized clinical trials of insulin glargine or NPH insulin in insulin-naïve, inadequately controlled patients. Female [n = 1251; mean glycated haemoglobin (HbA1c) level 8.99%, age 56.91 years, diabetes duration 9.84 years] and male patients (n = 1349; mean HbA1c 8.9%, age 57.47 years, diabetes duration 10.13 years) were started on and treated with insulin glargine or NPH insulin for 24-36 weeks. HbA1c and fasting blood glucose levels, percent achieving HbA1c target of <7% and insulin dose change were recorded.. For both men and women, HbA1c levels were significantly reduced over time (p < 0.001); a significantly greater HbA1c reduction was observed in men than in women (-1.36 vs. -1.22; p = 0.002). Significantly fewer women achieved target HbA1c of <7% (p < 0.001). At the study end, women had a significantly higher insulin dose/kg than men (0.47 vs. 0.42 U/kg; p < 0.001). The incidence rates of severe and severe nocturnal hypoglycaemia were significantly higher in women (3.28% vs. 1.85%; p < 0.05 and 2.24% vs. 0.59%; p < 0.001, respectively). Women were more likely to experience severe hypoglycaemia [odds ratio (OR) 1.80; 95% confidence interval (CI) 1.08, 3.00; p = 0.02] and severe nocturnal hypoglycaemia (OR: 3.80; 95% CI 1.72, 8.42; p = 0.001).. These observations confirm studies that found a smaller improvement in HbA1c and greater hypoglycaemia in women during insulin treatment. Physicians should be aware of the need to determine and closely monitor dosing, particularly in women, to optimize the balance between glycaemic control and hypoglycaemia risk.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Male; Middle Aged; Prevalence; Randomized Controlled Trials as Topic; Sex Factors; Treatment Outcome

Topics: Delayed-Action Preparations; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting

Because of the progressive nature of type 2 diabetes mellitus (T2DM), insulin therapy will eventually become necessary in most patients. Recent evidence suggests that maintaining optimal glycemic control by early insulin therapy can reduce the risk of microvascular and macrovascular complications in patients with T2DM. The present review focuses on relevant clinical evidence supporting the use of premixed insulin analogues in T2DM when intensifying therapy, and as starter insulins in insulin-naïve patients. Our aim is to provide relevant facts and clinical evidence useful in the decision-making process of treatment selection and individualized treatment goal setting to obtain sustained blood glucose control.

Topics: Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Insulin, Short-Acting; Treatment Outcome

It is uncertain whether the addition of biphasic insulin analogues to oral antidiabetic drugs (OADs) is as effective and safe as basal insulin in patients with type 2 diabetes mellitus (T2DM). We performed a systematic review to compare glycaemic control and selected clinical outcomes in T2DM patients inadequately controlled with OADs whose treatment was intensified by adding biphasic insulin aspart (BIAsp 30) or insulin glargine (IGlar).. The analysis included randomised controlled trials (RCTs) identified by a systematic literature search in medical databases (MEDLINE, EMBASE, The Cochrane Library and other sources) up to March 2013. Studies met the inclusion criteria if they compared BIAsp 30 vs. IGlar added to at least one OAD in T2DM patients. Trials applying different OADs in both treatment arms were also included. Results were presented as weighted mean difference (WMD) or odds ratio (OR) with a 95% confidence interval (CI).. Five trials, including a total number of 1758 patients followed up from 24 to 28 weeks, were identified. Quantitative synthesis demonstrated that BIAsp 30 reduced HbA1c level more efficiently than IGlar [5 RCTs; WMD (95% CI): -0.21% (-0.35%, -0.08%)]. Differences were observed in favour of BIAsp for lower mean prandial glucose increment [3 RCTs; WMD (95% CI): -14.70 mg/dl (-20.09, -9.31)]; no difference was observed for fasting plasma glucose [3 RCTs; WMD (95% CI): 7.09 mg/dl (-15.76, 29.94)]. We found no evidence for higher risk of overall [2 RCTs; 63% vs. 51%; OR = 1.77 (0.91; 3.44)] and severe hypoglycaemic episodes [4 RCTs; 0.98% vs. 1.12%; OR (95% CI) = 0.88 (0.31, 2.53)] in the BIAsp 30 group as compared with IGlar group. Twice-daily administration of BIAsp 30 resulted in larger weight gain [2 RCTs; WMD (95% CI) = 1.78 kg (1.04; 2.52)].. BIAsp 30 added to OAD therapy results in a better glycaemic control as compared with IGlar in T2DM patients. BIAsp 30 use is associated with slightly larger weight gain but no rise in risk of severe hypoglycaemic episodes.

Topics: Administration, Oral; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Postprandial Period; Randomized Controlled Trials as Topic; Treatment Outcome; Weight Gain

There is currently a lack of evidence from direct comparisons of treatment outcomes with lixisenatide versus neutral protamine Hagedorn (NPH)-insulin in type 2 diabetes mellitus (T2DM) patients with suboptimal glycaemic control with oral antidiabetic drugs (OADs). Hence, the current analysis indirectly compared available evidence on the risk of hypoglycaemia and weight change between lixisenatide and NPH-insulin based on randomized controlled trial (RCT) data with exenatide, insulin glargine and placebo as common references.. A systematic search of PubMed, Embase, the Cochrane database and clinical registries identified English- and German-language articles published from January 1980 to October 2012 reporting data from RCTs. Only publications of trials that reported outcomes from 24 to 30 weeks comparing glucagon-like peptide-1 receptor agonists or basal insulin versus another antidiabetic agent or placebo were included. Hypoglycaemia, patients at glycated haemoglobin (HbA1c) target and discontinuations due to adverse events (AEs) were treated as binary variables, with risk ratios and odds ratios (ORs) calculated. HbA1c and body weight were treated as continuous variables with difference in mean change from baseline (MD) calculated. Meta-analyses were performed with random effects models and indirect comparisons were performed according to Bucher's method.. Seven RCTs (n=3,301 patients) comparing the efficacy and safety of lixisenatide, exenatide, insulin glargine and NPH-insulin with different antidiabetic treatments in adult patients with T2DM were included in the final analysis. In the adjusted indirect comparison, there was a significant difference in symptomatic hypoglycaemia (OR = 0.38; 95% CI = [0.17, 0.85]) and in confirmed hypoglycaemia (OR = 0.46; 95% CI = [0.22, 0.96]) favouring lixisenatide over NPH-insulin and comparable changes in HbA1c from baseline (MD = 0.07%; 95% CI = [-0.26%, 0.41%]). In contrast to NPH-insulin, there was a significant reduction in body weight with lixisenatide (MD = -3.62 kg; 95% CI = [-5.86 kg, -1.38 kg]) at study completion. The number of discontinuations due to AEs numerically favoured NPH-insulin over lixisenatide (OR = 2.64; 95% CI = [0.25, 27.96]), with a broad confidence interval.. Lixisenatide treatment was associated with a lower risk of hypoglycaemia and a greater weight loss compared with NPH-insulin. Glycaemic control with lixisenatide treatment was comparable with NPH-insulin. These data suggest that lixisenatide is a beneficial treatment option for T2DM patients with inadequate glycaemic control on OADs, and is associated with reduced risk of hypoglycaemia and weight gain.

Topics: Adult; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin, Isophane; Metformin; Peptides; Sulfonylurea Compounds; Treatment Outcome

To evaluate the effectiveness and safety of dipeptidyl peptidase-4 (DPP-4) inhibitors versus intermediate-acting insulin for adults with type 2 diabetes mellitus (T2DM) and poor glycaemic control despite treatment with two oral agents.. Studies were multicentre and multinational.. Ten studies including 2967 patients with T2DM.. Studies that examined DPP-4 inhibitors compared with each other, intermediate-acting insulin, no treatment or placebo in patients with T2DM.. Primary outcome was glycosylated haemoglobin (HbA1c). Secondary outcomes were healthcare utilisation, body weight, fractures, quality of life, microvascular complications, macrovascular complications, all-cause mortality, harms, cost and cost-effectiveness.. 10 randomised clinical trials with 2967 patients were included after screening 5831 titles and abstracts, and 180 full-text articles. DPP-4 inhibitors significantly reduced HbA1c versus placebo in network meta-analysis (NMA; mean difference (MD) -0.62%, 95% CI -0.93% to -0.33%) and meta-analysis (MD -0.61%, 95% CI -0.81% to -0.41%), respectively. Significant differences in HbA1c were not observed for neutral protamine Hagedorn (NPH) insulin versus placebo and DPP-4 inhibitors versus NPH insulin in NMA. In meta-analysis, no significant differences were observed between DPP-4 inhibitors and placebo for severe hypoglycaemia, weight gain, cardiovascular disease, overall harms, treatment-related harms and mortality, although patients receiving DPP-4 inhibitors experienced less infections (relative risk 0.72, 95% CI 0.57 to 0.91).. DPP-4 inhibitors were superior to placebo in reducing HbA1c levels in adults with T2DM taking at least two oral agents. Compared with placebo, no safety signals were detected with DPP-4 inhibitors and there was a reduced risk of infection. There was no significant difference in HbA1c observed between NPH and placebo or NPH and DPP-4 inhibitors.. PROSPERO # CRD42013003624.

Topics: Diabetes Mellitus, Type 2; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Incretins; Insulin; Insulin, Isophane; Treatment Outcome

Excellent glycaemic control is essential in pregnancy to optimise maternal and foetal outcomes. The aim of this review is to assess the efficacy and safety of insulin analogues in pregnancy. Insulin lispro and insulin aspart are safe in pregnancy and may improve post-prandial glycaemic control in women with type 1 diabetes. However, a lack of data indicating improved foetal outcomes would suggest that there is no imperative to switch to a short-acting analogue where the woman's diabetes is well controlled with human insulin. There are no reports of the use of insulin glulisine in pregnancy and so its use cannot be recommended. Most studies of insulin glargine in pregnancy are small, retrospective and include women with pre-existing diabetes and gestational diabetes. There appear to be no major safety concerns and so it seems reasonable to continue insulin glargine if required to achieve excellent glycaemic control. A head-to-head comparison between insulin detemir and NPH insulin in women with type 1 diabetes showed that while foetal outcomes did not differ, fasting plasma glucose improved with insulin detemir without an increased incidence of hypoglycaemia. The greater evidence base supports the use of insulin detemir as the first line long-acting analogue in pregnancy but the lack of definitive foetal benefits means that there is no strong need to switch a woman who is well controlled on NPH insulin. There seems little justification in using long acting insulin analogues in women with gestational diabetes or type 2 diabetes where the risk of hypoglycaemia is low.

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Dose-Response Relationship, Drug; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Pregnancy; Pregnancy in Diabetics; Randomized Controlled Trials as Topic; Treatment Outcome

The aim of this review is to summarize the clinical efficacy, tolerability and safety data of insulin detemir, and compare its use with that of neutral protamine Hagedorn (NPH) insulin in randomized controlled trials in people with type 1 or type 2 diabetes. A literature search was conducted with PubMed using predefined search terms. Studies were included if they met the following criteria: randomized, controlled trial, comparison of insulin detemir with NPH insulin, non-hospitalized adults aged ≥18 years with either type 1 or type 2 diabetes, and study duration of ≥12 weeks. The following types of studies were excluded: non-randomized controlled trials, studies of mixed cohorts of patients with type 1 or type 2 diabetes that did not report results separately, pharmacokinetic/pharmacodynamic studies, reviews, pooled or meta-analyses or health-economic analyses. Fourteen publications met the inclusion criteria. Nine studies in people with type 1 diabetes and three studies in people with type 2 diabetes, using insulin detemir in a basal-bolus regimen were included. Two studies were in people with type 2 diabetes using insulin detemir with oral antidiabetes medicines. In 14 studies of people with type 1 or type 2 diabetes, insulin detemir treatment provided similar or better glycaemic control, lower within-subject variability, similar or lower frequency of hypoglycaemia and less weight gain when compared with NPH insulin.

Topics: Adult; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Insulin, Regular, Human; Isophane Insulin, Human; Randomized Controlled Trials as Topic; Weight Gain

To compare the impact of diabetes duration on hypoglycaemia in patients with type 2 diabetes mellitus (T2DM) treated with insulin glargine or NPH insulin.. A pooled analysis of 24-week patient level data from randomized controlled studies comparing once-daily insulin glargine with once-daily NPH insulin in insulin-naïve adult patients with T2DM was performed, stratifying patients into quartiles by duration of diabetes: <5.8 years; 5.8 to <9.2 years; 9.2 to <14 years and ≥14 years. Daytime and nocturnal hypoglycaemia events were evaluated.. Data from 2330 patients in four randomized controlled trials were included in the analysis; 1258 treated with insulin glargine and 1072 with NPH insulin. The rates of daytime hypoglycaemia were similar for insulin glargine and NPH insulin, irrespective of disease duration. Patients with longer T2DM duration treated with glargine experienced greater glycated haemoglobin A1c (HbA1c) reductions. Rates of severe nocturnal hypoglycaemia and nocturnal hypoglycaemia [self-monitored blood glucose < 70 mg/dl (3.89 mmol/l) and < 50 mg/dl (2.78 mmol/l)] were all significantly and positively correlated with the duration of diabetes for patients treated with NPH insulin but not with insulin glargine. Despite improvements in HbA1c, rates of symptomatic nocturnal hypoglycaemia were significantly lower with insulin glargine than with NPH insulin in patients with longer T2DM duration.. There is a lower risk for nocturnal hypoglycaemia with insulin glargine than with NPH insulin. When considering diabetes duration, insulin glargine (compared to NPH insulin) may be particularly beneficial in patients with a longer duration of T2DM.

Topics: Analysis of Variance; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Factors; Time Factors

During the past 10 years, several new basal insulin analogs have been developed. There has been for 3 years controversy on the potential increased risk for cancer with insulin glargine, which ceased with the publication of the ORIGIN trial in 2012. In insulin-treated persons with type 2 diabetes, it is usual to recommend that plasma insulin concentrations remain within a 50-200 pmol/L range in order to avoid overinsulinization, a potential causative factor for increased mitogenicity. Such concentrations are achieved when daily doses of insulin glargine or NPH insulin approximate 0.4 units/kg. However, the total plasma insulin concentrations are much greater in persons treated with insulin detemir and especially insulin degludec. These insulins derive their protracted action from the insertion of a long chain fatty acid moiety to the insulin molecule thereby increasing albumin binding. As a consequence, in persons with type 2 diabetes, stable total plasma concentrations as high as either 1600 or 6000 pmol/L are observed for insulin detemir or degludec, respectively. At present, the free to bound ratio of plasma insulin concentrations remains unknown for these two compounds. A first requirement is to understand how these insulins are eliminated or degraded and secondly to quantify the respective contributions of the free and bound fractions. Therefore, prior to early phase 2 or 3 randomized clinical trials, a better comprehension of the metabolism of all the new insulins would be invaluable.

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Weight Gain

Primary goals in the treatment of type 2 diabetes mellitus (T2DM) include lowering blood glucose levels sufficiently to prevent micro- and macrovascular complications while limiting side effects, such as hypoglycemia and excessive weight gain. Patients with T2DM are typically treated initially with oral antidiabetes agents; however, as the disease progresses, most will require insulin to maintain glycemic control. Often insulin therapy is initiated with basal insulin, and the objective of this article is to present the conceptual aspects of basal insulin therapy and use these concepts to illustrate important clinical aspects. This will be accomplished within a broader contextual discussion of the normal physiologic patterns of insulin secretion, which consist of sustained levels of basal insulin production throughout the day, superimposed with bursts of insulin secretion following a meal (termed bolus or prandial insulin secretion) that slowly decay over 1 to 3 hours. Long-acting basal insulin analogs form a key component of basal-bolus therapy and provide basal support for patients with T2DM. Insulin therapy is often initiated with basal insulin, and newer long-acting analogs, such as insulin glargine and insulin detemir, provide steady, reliable basal insulin coverage in addition to significant advantages over traditional long-acting insulins. This article will integrate conceptual aspects of basal insulin therapy in the context of physiology, molecular pharmacology, and clinical implications of modern basal insulin analogs to provide a foundational understanding of basal insulin biology and physiology.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Homeostasis; Humans; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Liver; Signal Transduction

Oral hypoglycaemic agents become less effective as beta cell function declines. Thus many patients with type 2 diabetes will ultimately require treatment with insulin. There are two main approaches to starting insulin: (a) as a basal supplement with an intermediate to long-acting preparation (NPH, glargine or detemir) plus oral agents; (b) as a premixed insulin regimen. Almost all the studies have shown similar glucose control with both NPH and the new insulin analogs. Further analyses between these insulins have documented significant reductions in hypoglycaemia especially at night with the insulin analogs. The weight gain is an important issue in patients with diabetes. It appears that insulin detemir studies have reported weight neutrality or less weigh gain or even weight loss. However, most insulin glargine studies have reported a weight gain. On the other hand insulin analogs have the important disadvantage of high cost. It is important to take in to account all the above factors such as cost, weight gain, number of insulin injections and hypoglycaemia while prescribing insulin.

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Weight Gain

The treatment of type 2 diabetes mellitus (T2DM) has been revolutionized by the introduction of novel therapeutic regimens following the clinical approval of the long-acting basal insulin glargine 10 years ago, followed by insulin detemir and, more recently, agents that target the glucagon-like peptide (GLP)-1 system with dipeptidyl peptidase 4 (DPP-4)-resistant products, such as liraglutide and exenatide, and DPP-4 inhibitors, such as sitagliptin, saxagliptin, alogliptin, and vildagliptin. The position and clinical efficacy of the GLP-1 mimetics are less well understood, however, and how they should be best used in the context of the established clinical efficacy of long-acting insulin analogs is yet to be defined. The aim of this review is to provide a summary of the efficacy, safety, and weight changes associated with long-acting insulin analogs (insulin glargine and insulin detemir) and two GLP-1 mimetics (exenatide and liraglutide). MEDLINE, EMBASE, and BIOSIS databases were searched with a timeframe of January 1, 2003-January 12, 2009 using the following terms: "Insulin glargine," with the co-indexing terms "LANTUS" and "HOE901"; "Insulin detemir," with the co-indexing term "Levemir"; "Exenatide"; and "Liraglutide." This literature review demonstrates that GLP-1 and basal insulin therapies are effective treatment options for insulin-naïve patients with suboptimal glycemic control with oral hypoglycemic agents. There are potential advantages of basal insulin and GLP-1 therapies in particular populations of patients. Further comparative data are needed to fully investigate the relative positioning of these therapies within the T2DM treatment paradigm.

Topics: Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

To review the cost-effectiveness of biphasic insulin aspart (BIAsp 30) compared to other insulin regimens in the treatment of type 2 diabetes based on published literature.. The electronic databases MEDLINE, EMBASE, the Cochrane Library and EconLit and a selection of congress/meeting databases were systematically searched using combinations of search terms designed to identify publications describing cost-effectiveness analyses of BIAsp 30 in patients with type 2 diabetes. Searches were limited to studies in humans, and published in the English language between January 1999 and July 2009. All records were screened for inclusion in the review.. Seven published cost-effectiveness analyses and ten abstracts were identified. One was a health technology assessment from the UK, which evaluated cost-effectiveness using the UKPDS Outcomes Model and meta-analysis of published clinical trials and concluded that premixed insulin analogs were unlikely to be cost-effective versus insulin glargine or biphasic human insulin. In all other studies the cost-effectiveness of BIAsp 30 versus other insulin regimens was assessed using the validated CORE Diabetes Model and outcomes from either the INITIATE randomized controlled trial, or the PRESENT or IMPROVE observational studies. However, notable limitations include the fact that all cost-effectiveness analyses to date have been performed using a single model and that a number of these are based on data from observational studies rather than randomized controlled trials. Nevertheless, long-term clinical and economic outcomes were reported for several countries: UK, US, Sweden, Saudi Arabia, Poland, South Africa, South Korea and China. BIAsp 30 was associated with improvements in quality-adjusted life expectancy in all countries. Estimates of direct costs varied according to country and comparator, but incremental cost-effectiveness ratios for the US and UK were USD 46 533 and GBP 6951 per quality-adjusted life year gained for BIAsp 30 versus insulin glargine.. Although cost-effectiveness data on BIAsp 30 are scarce the majority of the analyses identified in this review suggest that BIAsp 30 is likely to be cost-effective compared to insulin glargine and biphasic human insulin across a wide range of settings, and under certain circumstances would be a dominant treatment option.

Topics: Biphasic Insulins; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Middle Aged

Basal insulin analogues are an effective treatment for type 2 diabetes with proven efficacy, and insulins NPH, detemir and glargine have shown comparable glycaemic control. However, pharmacokinetics and clinical studies highlight the advantages of insulins detemir and glargine over insulin NPH in terms of once-daily dosing, reduced risk of hypoglycaemia, reduced within-patient variability, appropriate duration of action and simple titration. Insulin detemir has demonstrated the additional advantage of less weight gain. Introduction of insulin detemir, at the appropriate time, can help empower patients to reach glycaemic targets, with a reduced risk of hypoglycaemia and less weight gain.

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

This pedagogical review illustrates the differences between pharmacokinetic (PK) and pharmacodynamic (PD) measures, using insulin therapy as the primary example. The main conclusion is that PD parameters are of greater clinical significance for insulin therapy than PK parameters. The glucose-clamp technique, the optimal method for determining insulin PD, is explained so that the reader can understand the important studies in the literature. Key glucose-clamp studies that compare two basal insulin analogues - insulin glargine and insulin detemir - to Neutral Protamine Hagedorn insulin and to each other are then presented. The review further explains how PD parameters have been translated into useful clinical concepts and simple titration algorithms for everyday clinical practice. Finally, the necessity of overcoming patient and/or physician barriers to insulin therapy and providing continuing education and training is emphasised.

Topics: Blood Glucose; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Glucose Clamp Technique; Half-Life; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin Secretion; Insulin, Isophane; Insulin, Long-Acting

Most guidelines suggest that failure of oral antidiabetic drugs should be followed by the addition of a basal insulin with aggressive titration of the dose. In most countries, neutral protamine Hagedorn (NPH)-insulin, glargine and detemir are the only choices. Clinical trials show that the metabolism and metabolic outcomes after treatment with intermediate- or long-acting insulins differ little. Despite this, the hypoglycaemic potential, effect on body weight and adherence to insulin treatment may affect the choice of basal insulin. Adherence seems to be negatively correlated to the prescribed dose and the number of injections. Furthermore, the choice of basal insulin might be influenced by the number of units necessary to achieve the goal for HbA1c.. By searching the literature systematically, we identified all randomised clinical trials comparing long-acting insulins (human NPH-insulin and the analogues glargine and detemir) for the treatment of type 2 diabetes conducted over the last 10 years. We continued by reviewing only studies in which similar antihyperglycaemic potential of the treatments was achieved.. According to the inclusion criteria for this review, all drugs were efficacious regarding the main purpose of decreasing glycaemia. For an equal efficacy, we were able to detect other differences between the treatments and, furthermore, an estimate on the number of units of insulin needed to achieve comparable glycaemic control.. The analysis confirmed a favourable profile of both analogues regarding hypoglycaemia. For detemir, we additionally identified a favourable profile regarding weight gain and need for an increased number of units of insulin to achieve comparable glycosylated haemoglobin (HbA1c) responses. We conclude that the efficacy of insulin treatment seems to vary little between the available products, however doses needed to achieve similar effects vary; units used per HbA1c reduction could be a relevant parameter for the choice of insulin.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Time Factors; Treatment Outcome; Weight Gain

To estimate absolute and relative incidence rates of hypoglycaemia when using once-daily evening or morning regimens of insulin glargine (glargine) versus once-daily evening NPH insulin (NPH) using individual patient data (IPD).. Randomized controlled trials with accessible IPD and including white European people with type 2 diabetes (T2DM) using glargine or NPH once-daily (with oral glucose-lowering drugs) were identified. Two study pools were analysed: evening glargine versus evening NPH (pool 1); and morning glargine versus evening NPH (pool 2). The number-needed-to-treat to avoid hypoglycaemia was calculated for glargine versus NPH.. In study pool 1 (n = 2711), the risk of nocturnal hypoglycaemia was approximately halved with glargine compared with NPH [odds ratios (OR): 0.44-0.52, p < 0.001-0.047]. This led to a significant reduction in anytime risk of symptomatic hypoglycaemia [plasma glucose (PG) <3.9 mmol/l, OR: 0.64, p = 0.018; PG <2.0 mmol/l, OR: 0.51, p < 0.001]. In study pool 2 (n = 470), although a strong numerical reduction in all types of nocturnal hypoglycaemia was observed (OR: 0.16-0.64), statistical significance was reached only for symptomatic hypoglycaemia with PG <3.9 mmol/l (p < 0.001). Eight (pool 1) or five (pool 2) people with T2DM needed to use glargine rather than NPH to avoid one person from experiencing a nocturnal symptomatic hypoglycaemic event within a median of about 25 weeks of starting insulin.. This meta-analysis of open-label studies provides confidence that reductions of around 50% of risk for nocturnal hypoglycaemia can be achieved with using glargine instead of NPH.

Topics: Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Randomized Controlled Trials as Topic; Risk Assessment; Treatment Outcome

Insulin is recommended as a second-line treatment after diet and metformin fail to reach and/or maintain glycemic targets considered to minimize the risk for long-term diabetic complications. Hypoglycemia and the fear of developing hypoglyce-mia, however, remain substantial barriers to the initiation and optimal use of insulin.. The aim of this study was to compare biphasic insulin aspart 30 (BIAsp 30) with biphasic human insulin 30 (BHI 30) with respect to glycemic control and the risk for hypoglycemia using a meta-analysis of clinical trials comparing these insulins in patients with type 2 diabetes mellitus (T2DM).. We included all published and unpublished, randomized, controlled trials in adult patients with T2DM (treatment duration > or = 12 weeks) for which individual patient data were available. All clinical databases and local trial registries of Novo Nordisk A/S (Soeborg, Denmark) were searched to identify clinical trials comparing the 2 products. The predefined primary end point of the study was the overall rate of nocturnal hypoglyce-mia (major, minor, and symptoms-only hypoglycemia occurring from 12:00-6:00 AM). Hypoglycemia was analyzed using a negative binomial distribution model, accounting for exposure time. Glycemic end points were analyzed at 12 to 16 weeks of treatment using ANCOVA, adjusting for baseline. Secondary safety end points were the rates of major hypoglycemia (hypoglycemia requiring third-party assistance), minor hypoglycemia (symptoms confirmed by plasma glucose [PG] <3.1 mmol/L), daytime hypoglycemia (major, minor, and symptoms-only hypoglycemia occurring from 6:01 AM-11:59 PM), overall hypoglycemia (the sum of all major, minor, and symptoms-only episodes), and change in weight from baseline to 12 to 16 weeks of treatment. Secondary efficacy end points were changes in glycosylated hemoglobin (HbA(1c)), fasting PG (FPG), postprandial PG increment (averaged over breakfast, lunch, and dinner), and insulin dose.. Nine randomized, parallel or crossover trials were included (N = 1674; male sex, 57%; mean [SD] age, 61.0 [10.6] years; body mass index, 26.7 [4.6] kg/m(2); HbA(1c), 8.1% [1.4%]; duration of diabetes, 10.9 [7.9] years). Rates of overall hypoglycemia were not significantly different (rate ratio [RR] = 1.08; 95% CI, 0.94-1.24; P = NS) between treatments. BIAsp 30 had a 50% lower rate of nocturnal hypoglycemia than BHI 30 (RR = 0.50; 95% CI, 0.38-0.67; P < 0.01), whereas the rate of daytime hypoglycemia was 24% lower for BHI 30 (RR = 1.24; 95% CI, 1.08-1.43; P < 0.01). The likelihood of major hypo-glycemia was significantly lower with BIAsp 30 compared with BHI 30 (odds ratio = 0.45; 95% CI, 0.22-0.93; P < 0.05). BIAsp 30 was associated with reduced PPG increment (averaged over breakfast, lunch and dinner) compared with BHI 30 (treatment difference, -0.31; 95% CI, -0.49 to -0.07; P < 0.01). There was a significantly larger reduction in FPG associated with BHI 30 (treatment difference, 0.63; 95% CI, 0.31-0.95; P < 0.01). However, no significant treatment difference was found for HbA(1c) (treatment difference, 0.04; 95% CI, -0.02 to 0.10; P = NS).. This meta-analysis found BIAsp 30 to be associated with a significantly lower rate of nocturnal and major hypoglycemia, but a significantly increased risk for daytime hypoglycemia, compared with BHI 30 at a similar level of HbA(1c) in patients with T2DM.

Topics: Adult; Aged; Biphasic Insulins; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Risk; Time Factors

Recent epidemiological studies suggest that treatment with insulin glargine (A21Gly,B31Arg,B32Arg human insulin) may promote cancer growth. The present meta-analysis was performed to assess the risk of cancer during treatment with insulin detemir (B29Lys(epsilon-tetradecanoyl),desB30 human insulin), another long-acting insulin analogue.. This meta-analysis was performed in a population of 8,693 patients with type 1 or type 2 diabetes, who were included in Novo Nordisk-sponsored, randomised and controlled diabetes trials of at least 12 weeks in duration that compared insulin detemir with NPH insulin or insulin glargine. In a blinded manner, the adverse events with suspected treatment-emergent malignant tumours were obtained from these studies under three system-organ classes: 'Neoplasms benign, malignant and unspecified (including cysts and polyps)', 'Neoplasm' and 'Surgical and medical procedures'. Conditional ORs were estimated applying both the Mantel-Haenzel and Peto methods to ensure robustness of results.. Separate analyses were performed for trials comparing insulin detemir with NPH insulin and insulin detemir with insulin glargine. In the first analysis, 16 studies were included with a total of 3,983 patients treated with insulin detemir and 2,661 patients treated with NPH insulin. In the second analysis, five studies were included with a total of 1,219 patients treated with insulin detemir and 830 patients treated with insulin glargine. The estimated OR for a cancer diagnosis between NPH insulin and insulin detemir was statistically significantly >1, with the ratio favouring insulin detemir. There was a more than twofold higher cancer occurrence in the NPH insulin-treated population. For the insulin detemir comparison with insulin glargine, there was a non-significant difference in ORs in favour of insulin detemir.. In these randomised controlled diabetes trials, patients treated with insulin detemir had a lower or similar occurrence of a cancer diagnosis compared with patients treated with NPH insulin or insulin glargine, respectively.

Topics: Adult; Aged; Body Mass Index; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Incidence; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Neoplasms; Randomized Controlled Trials as Topic

Diabetes mellitus is a major public health problem, in particular because of long-term complications affecting essential organs, such as the eyes and kidneys, which can lead to a reduction in life expectancy and high healthcare costs. The number of individuals with diabetes mellitus is projected to rise worldwide from 171 million people in 2000 to 366 million people in 2030. With the number of patients with diabetes continually growing, the burden of pressure on worldwide health systems is huge. Accordingly, regulatory and marketing approvals of new medicines are beginning to incorporate economic evaluation techniques to determine their cost-effectiveness. Overall, the studies included in this review show that the initiation of insulin glargine is cost-effective and is expected to lead to substantial improvements in both life years (LYs) and quality-adjusted LYs compared with neutral protamine Hagedorn insulin.

Topics: Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Drug Costs; Health Care Costs; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Quality-Adjusted Life Years

PRESENT (Physicians' Routine Evaluation of Safety & Efficacy of NovoMix 30 Therapy) is a 6-month observational study of safety and efficacy of biphasic insulin aspart 30 (BIAsp 30) in 31,044 type 2 diabetes patients from 15 countries. The aim of this article is to describe the study protocol and assess baseline characteristics of patients in various countries according to diabetes duration (<5 years, 5 to or=20 years), to improve treatment decisions in clinical practice. Glycaemic control was similar across all groups: HbA1c 9.3-9.4%; fasting plasma glucose 11.3-11.6 mmol/L; postprandial glucose 15.9-16.3 mmol/L. Major hypoglycaemia was reported by 5% of all patients, minor hypoglycaemia increased with diabetes duration (25.4-30.3%); overall hypoglycaemia rate was 6.7 events/patient/year. Complications increased with diabetes duration; the most reported were hypertension (40.6-71.0%) and hyperlipidaemia (39.4-56.6%). Of patients 38% previously received OADs only, 28% insulin only, 19% insulin with OADs, and 13% received no therapy. Glycaemic control appeared independent of diabetes duration. HbA1c was well above targets and the clinical inertia was quite apparent; even patients with diabetes for <5 years had high HbA1c levels. Patients suffered high rates of complications and hypoglycaemia before starting BIAsp 30 therapy.

Topics: Biphasic Insulins; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Multicenter Studies as Topic; Patient Selection; Research Design

Basal insulin administered to type-2 diabetic patients with poor glycaemic control when managed with oral anti-diabetics (OADs) alone can lead to an increased risk of weight gain and hypoglycaemia. In the absence of head-to-head trials, an indirect comparison of the once-daily insulin detemir with insulin glargine was conducted on the following outcomes: weight gain, hypoglycaemic episodes, and HbA(1c).. Parallel-group randomised controlled trials of at least 20 weeks duration that compared once-daily evening glargine or detemir with a common comparator, neutral protamine Hagedorn insulin (evening), were selected. Trials focused on insulin-naïve, type-2 diabetic patients poorly controlled with OAD. Five open-label trials were identified (n = 2,092 patients; n = 1 detemir and n = 4 glargine trials), with an indirect comparison of glargine (n = 869 patients) and detemir trials (n = 169 patients) carried out using meta-regression to control for covariates. Weight gain was analysed as weighted mean differences (WMD), hypoglycaemic episodes as odds ratios (OR), and HbA(1c) at the end of study as standardised mean differences (SMD).. Patients receiving evening detemir gained significantly less weight (unadjusted WMD -1.22 kg, 95% CI -2.15, -0.29 kg; p = 0.010) and significantly fewer of them experienced hypoglycaemic episodes versus evening glargine (unadjusted OR 0.52, 95% CI 0.28, 0.98; p = 0.044). There was no significant difference between treatments for the mean HbA(1c) level at study endpoint (unadjusted SMD 0.09, 95% CI -0.16, 0.33; p = 0.480).. Once-daily use of insulin detemir resulted in significantly less weight gain and fewer hypoglycaemic episodes than glargine, while maintaining clinically appropriate HbA(1c) levels in type-2 diabetic patients currently receiving OAD.

Topics: Aged; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Randomized Controlled Trials as Topic; Regression Analysis; Weight Gain

To increase awareness regarding the different types of insulin available and provide discussion regarding how each type of insulin can address the needs of diverse patients in terms of their unique requirements, preferences, medical history and lifestyle concerns.. New classes of antidiabetes medications, the development of insulin analogues and novel insulin delivery systems, provide more options for the management of type 2 diabetes. Given the inevitable progression of beta-cell dysfunction, along with the relatively limited glucose-lowering capacity of other agents, many patients will eventually require insulin for optimal glycaemic management. However, patients and physicians often fail to initiate insulin early enough during the progression of disease to maintain the recommended levels of glycaemic control. The inherent properties of the new insulin analogues, more physiological and user-friendly time-action profiles compared with older human insulin formulations, may partly address the barriers to insulin use. Insulin analogues include rapid acting (for prandial glycaemic control), long acting (for basal insulin coverage) and premixed insulin analogues, which combine both a rapid acting and an extended duration component in a single insulin formulation. Various case-based scenarios on initiating and intensifying therapy with insulin analogues will be presented.. Development of an individualised treatment plan for initiation of insulin is a critical step in achieving target glycaemic levels in patients with type 2 diabetes.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Injections; Insulin; Insulin Infusion Systems; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome

We systematically analysed evidence from randomized controlled trials (RCTs) examining the safety and efficacy of neutral protamine Hagedorn (NPH) insulin and glargine in the management of adults with Type 2 diabetes.. Studies were identified by searching medline (1966-March 2007), embase (1974-2007), American Diabetes Association abstract database and the Cochrane Central Register of Controlled Trials using Medical Subject Headings (MeSH) diabetes mellitus, Type 2, insulin, insulin isophane, hypoglycaemic agents and the keywords glargine and NPH. Data on study design, participants, fasting plasma glucose (FPG), glycated haemoglobin (HbA(1c)), body weight and hypoglycaemia were independently abstracted by two investigators using a standardized protocol.. Data from a total of 4385 participants in 12 RCTs were pooled using a random-effects model. The mean net change (95% confidence interval) for FPG, HbA(1c) and body weight for patients treated with NPH insulin as compared with glargine was 0.21 mmol/l (-0.02 to 0.45), 0.08% (-0.04 to 0.21) and -0.33 kg (-0.61 to -0.06), respectively, with negative values favouring NPH and positive values favouring glargine. More participants experienced symptomatic and nocturnal hypoglycaemia on NPH than glargine, but there was no significant difference in confirmed or severe episodes.. We identified no difference in glucose-lowering between insulin glargine and NPH insulin, but less patient-reported hypoglycaemia with glargine and slightly less weight gain with NPH in adults with Type 2 diabetes.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Randomized Controlled Trials as Topic; Statistics as Topic; Weight Gain

Topics: Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin, Isophane; Insulin, Long-Acting; Treatment Outcome

Long-acting insulin analogues, in comparison with NPH insulin, should warrant a greater reproducibility of absorption after subcutaneous injection, providing better metabolic control with reduced hypoglycaemic risk. Aim of the present meta-analysis is the assessment of differences with respect to HbA1c, incidence of hypoglycaemia, weight gain, between NPH human insulin and each long-acting analogue.. All randomized controlled trials (RCTs) with a duration >12 weeks comparing long-acting insulin analogues (detemir or glargine) with NPH insulin in type 2 diabetic patients were retrieved; data on HbA1c and BMI at endpoint, and incidence of any, symptomatic, nocturnal, and severe hypoglycaemia, were extracted and meta-analysed.. A total of 14 RCTs was retrieved and included in the analysis. Long-acting analogues did not produce any significant improvement of HbA1c, in comparison with NPH human insulin. When trials with different analogues were analysed separately, NPH showed a significant superiority (by 0.1%) over detemir, but not over glargine. When analysing the effect of long-acting analogues on body weight, detemir, but not glargine, was associated with a significantly smaller weight gain than human insulin Both analogues were associated with a reduced risk for nocturnal and symptomatic hypoglycaemia (OR: 0.46[0.38-0.55] and 0.69[0.60-0.80]; all p<0.01).. Long-acting insulin analogues in type 2 diabetic patients does not seem to provide a better glycemic control in comparison with NPH insulin, whereas it reduces the risk of nocturnal and symptomatic hypoglycemia. Detemir, but not glargine, could be associated with smaller weight gain than NPH insulin.

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Middle Aged; Randomized Controlled Trials as Topic

A recent meta-analysis evaluated trials of the rapid-acting analogues insulin lispro and insulin aspart, performed before the introduction of the basal analogues, insulin glargine and insulin detemir. This article reviews the effect of rapid-acting and basal insulin analogues separately and in combination, relative to human insulin. Outcomes evaluated include HbA(1c), hypoglycaemia, postprandial glucose (PPG), and weight changes. Results from trials that matched defined criteria are presented in tables. In type 1 diabetes, compared with human insulin, the rapid-acting analogues generally reduced hypoglycaemia and postprandial glucose, whereas the basal analogues tended to reduce hypoglycaemia -- particularly nocturnal hypoglycaemia. Weight gain may also be reduced with basal analogues, compared with human basal insulin. In type 2 diabetes, premix rapid-acting analogues controlled postprandial glucose better than human insulin mixes; basal analogues used as basal-only therapy reduced hypoglycaemia compared with NPH insulin; and some advantages were apparent with analogues in basal-bolus therapy. Whilst the benefits on individual metabolic and clinical outcomes appear modest, almost all studies report some advantage when using insulin analogues in type 1 and type 2 diabetes. Significant benefits, including PPG lowering with the rapid-acting analogues and the potential for reduction in cardiovascular risk, should be investigated further.

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Administration Schedule; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin Lispro; Insulin, Isophane; Insulin, Long-Acting; Postprandial Period; Randomized Controlled Trials as Topic

Despite indications from epidemiological trials that higher blood glucose concentrations are associated with a higher risk for developing micro- and macrovascular complications, evidence for a beneficial effect of antihyperglycaemic therapy in patients with type 2 diabetes mellitus is conflicting. Two large studies, the United Kingdom Prospective Diabetes Study (UKPDS) and the University Group Diabetes Program (UGDP), did not find a reduction of cardiovascular endpoints through improvement of metabolic control. The theoretical benefits of newer insulin analogues might result in fewer macrovascular and microvascular events.. To assess the effects of long-term treatment with long-acting insulin analogues (insulin glargine and insulin detemir) compared to NPH insulin in patients with type 2 diabetes mellitus.. Studies were obtained from computerised searches of MEDLINE, EMBASE, The Cochrane Library and communication with experts in the field as well as insulin producing companies.. Studies were included if they were randomised controlled trials in adults with diabetes mellitus type 2 and had a trial duration of at least 24 weeks.. Two authors independently assessed trial quality and extracted data. Pooling of studies by means of random-effects meta-analyses was performed.. Six studies comparing insulin glargine to NPH (Neutral Protamine Hagedorn) insulin and two studies comparing insulin detemir to NPH insulin were identified. In these trials, 1715 patients were randomised to insulin glargine and 578 patients to insulin detemir. Duration of the included trials ranged from 24 to 52 weeks. Metabolic control, measured by glycosylated haemoglobin A1c (HbA1c) as a surrogate endpoint, and adverse effects did not differ in a clinical relevant way between treatment groups. While no statistically significant difference for severe hypoglycaemia rates was shown in any of the trials, the rate of symptomatic, overall and nocturnal hypoglycaemia was statistically significantly lower in patients treated with either insulin glargine or detemir. No evidence for a beneficial effect of long-acting analogues on patient-oriented outcomes like mortality, morbidity, quality of life or costs could be obtained.. Our analysis suggests, if at all only a minor clinical benefit of treatment with long-acting insulin analogues for patients with diabetes mellitus type 2 treated with "basal" insulin regarding symptomatic nocturnal hypoglycaemic events. Until long-term efficacy and safety data are available, we suggest a cautious approach to therapy with insulin glargine or detemir.

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Randomized Controlled Trials as Topic

The efficacy benefits of biphasic insulin aspart formulation (BIAsp 30) in patients with diabetes mellitus have been reported in several studies. BIAsp 30 has been shown to be more effective in terms of glycaemic control than standard biphasic human insulin 30 (BHI 30). In addition to gauging the treatment in terms of clinical evidence of benefits provided, it is also important to evaluate the strength of the evidence supporting the therapeutic improvements offered by BIAsp 30. In this paper, we evaluated the strength of the available data that relate to the use of BIAsp 30 in the treatment of patients with type 2 diabetes based on a comprehensive literature review. Selected publications that provided relevant data were obtained via a literature search and from the manufacturer, Novo Nordisk. These were graded in terms of the strength of the evidence they provided using the Oxford Centre for Evidence-Based Medicine (CEBM) system in the following categories: (i) twice-daily use versus basal insulin; (ii) twice-daily use versus other treatments; (iii) once-daily use; (iv) thrice-daily use; (v) use in combination with thiazolidinediones; and (vi) use in comparison with BHI 30. A total of 30 publications for BIAsp 30 were identified and graded. For the majority of categories (four out of six), the evidence supporting the use of BIAsp 30 was given an overall CEBM grade of A (highest quality); evidence supporting clinical efficacy in the other two categories (twice-daily use versus basal insulin and thrice-daily BIAsp 30 administration) was graded B. In most of the studies examined, the efficacy of BIAsp 30 was evaluated in terms of glycaemic control (glycosylated haemoglobin [HbA(1c)] reduction, proportion of patients achieving HbA(1c) target of <6.5% or <7%, fasting blood glucose, blood glucose profile and/or prandial and postprandial glucose increments). In some studies, efficacy was further evaluated using plasma insulin and glucose infusion rates, plasma C-peptide levels, mean serum fructosamine levels, postprandial hyperlipidaemia, overall well-being, treatment satisfaction and quality of life. Safety was evaluated using physical and laboratory investigations and assessment of incidence of adverse events, including, in many of the studies reviewed, specific evaluation of those events known to be associated with antidiabetic treatment, hypoglycaemia and weight gain. Strong evidence was provided for better glycaemic control with BIAsp 30 without increases i

Topics: Biphasic Insulins; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Evidence-Based Medicine; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane

Primary care physicians are responsible for providing healthcare to most patients with type 2 diabetes. In this role, it is critical that physicians utilize a whole-patient treatment approach that includes lifestyle modifications and pharmacotherapy aimed to achieve glycemic control, in addition to the management of any comorbid conditions or risk factors for cardiovascular complications of diabetes. Due to the progressive nature of the disease, most patients with type 2 diabetes will eventually require insulin to achieve and maintain glycemic control, because of both increased insulin resistance and diminished secretory capacity of the pancreatic beta cells. Thus, physicians need to be knowledgeable about and comfortable with the use of insulin, as well as with educating patients and discussing any potential barriers to insulin therapy. The use of a stepwise approach--beginning with basal insulin therapy and adding prandial insulin if necessary--is simple, effective, and appropriate for use in many patients.

Topics: Diabetes Mellitus, Type 2; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Insulin; Insulin, Isophane; Insulin, Long-Acting; Life Style; Obesity; Physicians, Family; Risk Factors; Socioeconomic Factors; Treatment Outcome

This analysis first modeled the interaction between hypoglycemia and glycosylated hemoglobin (HbA1c) in clinical trials that compared insulin glargine (glargine) with human neutral protamine Hagedorn insulin (NPH) in patients with type 1 or type 2 diabetes mellitus. The model was then used to compare rates of hypoglycemia associated with use of these insulins.. Patient-level data from all randomized Phase III/IV clinical trials sponsored by the manufacturer of glargine that compared glargine and NPH and were available in May 2004 were included in the model. In addition, MEDLINE, EMBASE, and BIOSIS were searched for comparative randomized controlled trials of glargine and NPH using the terms insulin glargine, HOE 901, neutral protamine Hagedorn insulin, and NPH insulin. Studies were excluded from the analysis if patient-level data were not available. Unadjusted rates of symptomatic, confirmed, and severe hypoglycemia were compared with those derived from negative binomial regression analysis, which stratified the results by HbA1c at end point (with last observation carried forward), treatment, and duration of diabetes. In addition, the analysis was stratified by Phase III studies (which focused on determining tolerability and efficacy before regulatory approval) and Phase IV studies (which compared the clinical efficacy of the 2 insulins). The first month of the study was not included in the analysis because of continual adjustment of the insulin dose and maintenance of previous NPH in some studies.. Eleven sponsored randomized trials were included in the model (total of 5074 patients). Four other sponsored trials were not included because the databases were not finalized, and 3 investigator-initiated trials were not included because patient-level data were unavailable. Rates of hypoglycemia had a curvilinear relationship with HbAlc, increasing at lower end-point HbAlc values. In combined analyses of the studies of type 1 and type 2 diabetes, unadjusted rates of hypoglycemia were lower for glargine than NPH: 6.1% lower for all symptomatic hypoglycemia, 21.6% lower for confirmed hypoglycemia, and 23.9% lower for severe hypoglycemia (all, P < 0.05). When modeled using the negative binomial distribution with end-point HbA1c as a covariate, the corresponding results were 9.1% (P < 0.05), 26.6% (P < 0.001), and 30.0% (P = 0.08), respectively. When only Phase IV trials were analyzed, the relative reductions with glargine were 16.2% (P < 0.01), 40.8% (P < 0.01), and 46.8% (P < 0.05). The results of the separate analyses of studies of type 1 and type 2 diabetes were comparable.. Based on the results of this analysis, calculated unadjusted hypoglycemia event rates appear to underestimate the differences between glargine and NPH. In most of the present analyses, unadjusted rates were significantly lower with glargine than NPH. Adjustment for end-point HbA1c resulted in greater relative reductions in the risk of hypoglycemia for glargine compared with NPH. The adjusted risk reduction with glargine was highest in the Phase IV studies.

Topics: Binomial Distribution; Blood Glucose; Clinical Trials, Phase III as Topic; Clinical Trials, Phase IV as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Models, Statistical; Randomized Controlled Trials as Topic; Treatment Outcome

To compare the safety and efficacy of insulin detemir with that of neutral protamine Hagedorn (NPH) insulin in older (aged >/=65) and younger (aged 18-64) persons with type 2 diabetes mellitus (DM).. Pooled, post hoc analysis of data from three open-label, randomized studies.. Three multinational Phase III trials.. Four hundred sixteen older and 880 younger persons with DM, treated for 22 to 26 weeks with basal insulin plus mealtime insulin or oral agents.. Hemoglobin A(1c) (HbA(1c)), fasting plasma glucose, glucose variability, hypoglycemic episodes.. Mean treatment difference for HbA(1c) (insulin detemir-NPH insulin) indicated that insulin detemir was not inferior to NPH insulin for both age groups (0.035%, 95% confidence interval (CI)=-0.114-0.183 and 0.100%, 95% CI=-0.017-0.217, for older and younger persons, respectively). Relative risk of all hypoglycemic episodes (insulin detemir/NPH insulin) was 0.59 (95% CI-0.42-0.83) for older persons and 0.75 (95% CI-0.59-0.96) for younger persons. Adverse events were similar between treatments. Fasting plasma glucose was similar between treatments (mean treatment difference 0.97 mg/dL, 95% CI=-8.01-9.95, and 4.69 mg/dL, 95% CI=-2.30-11.67, for older and younger persons, respectively). Mean treatment difference for weight was -1.02 kg (95% CI -1.61 to -0.42) and -1.13 (95% CI -1.58 to -0.69) for older and younger persons, respectively.. Previously reported benefits of insulin detemir, particularly less hypoglycemia and less weight gain, compared with NPH insulin, were the same for older and younger persons with DM at similar levels of HbA(1c).

Topics: Aged; Blood Glucose; Clinical Trials, Phase III as Topic; Diabetes Complications; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Multicenter Studies as Topic; Randomized Controlled Trials as Topic

Basal insulin therapy is an integral part of the intensive management of type 1 diabetes and it is also often used in type 2 diabetes. An ideal insulin regimen in patients with diabetes would mirror the 24-h insulin profile of a non-diabetic person, thereby preventing hyperglycaemia without inducing hypoglycaemia. Until recently, available insulins have pharmacokinetic disadvantages, compared to physiological insulin secretion. Insulin detemir is a new basal insulin analogue recently available for commercial use in the UK. Clinical trials have demonstrated lower fasting plasma glucose levels, lower variability in plasma glucose, predictable action profile and a reduced risk of nocturnal hypoglycaemia and weight gain, compared to conventional basal insulins. This study reviews the properties and potential use of insulin detemir.

Topics: Blood Glucose; Body Weight; Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Treatment Outcome

The pharmacology, pharmacokinetics, efficacy and tolerability, safety, drug interactions, dosage and administration, cost, and place in therapy of insulin detemir are reviewed.. Insulin detemir is a long-acting, neutral, and soluble insulin analogue with a lower within-subject variability of fasting plasma glucose levels than isophane insulin human (NPH insulin) and insulin glargine. The lower within-subject variability of insulin detemir may decrease hypoglycemic events, especially nocturnal events, and may contribute to a decreased incidence of weight gain. In vivo, insulin detemir is 98-99% bound to albumin-one of the mechanisms contributing to its long duration of action. Several open-labeled, randomized, multicenter trials have been conducted comparing the safety and efficacy of insulin detemir to NPH insulin in patients with type 1 or type 2 diabetes mellitus. In most trials, patients were randomized to receive insulin on three different dosing schedules: basal insulin twice daily before breakfast and at bedtime, basal insulin at 12-hour intervals, or basal insulin before breakfast and dinner. Mealtime insulin was given as part of the basal-bolus therapy. Glycosylated hemoglobin values were similar in patients receiving insulin detemir or NPH insulin. Insulin detemir appears to be well tolerated. The most common adverse effects reported during clinical trials were hypoglycemia, headache, dizziness, and injection-site reactions.. Insulin detemir given once or twice daily as part of basal-bolus insulin therapy is at least as effective as NPH insulin in maintaining overall glycemic control in adult patients with type 1 or type 2 diabetes mellitus.

Topics: Adult; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Interactions; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting

The primary aim of insulin therapy is to replace endogenous insulin secretion in patients with type 1 or type 2 diabetes between meals and overnight as well as postprandially. The most frequently used insulin for basal therapy is the intermediate-acting neutral protamin Hagedorn (NPH) insulin, although it does not correspond to a physiological profile. Insulin glargine is a new extended-action recombinant insulin analog, which is absorbed slowly into the bloodstream, reaching peak action in about 4 h and maintaining this concentration profil for 24-30 h. Some studies demonstrated that insulin glargine reduces the incidence of hypoglycemia and is at least as effective as NPH insulin given once or twice daily. It is equally effective administered before breakfast, dinner or at bedtime. Similar absorption rates were recorded after subcutaneous injection in differents part of body. The continuous subcutaneous insulin infusion utilizing an external insulin infusion pump (CSII) is one approach to intensive insulin therapy. Some studies indicate that pump therapy is associated with improved glycemic control compared with traditional insulin therapies and with significant decreases in frequency of both mild and severe hypoglycemic episodes. The author summarizes the indication, the effect and side effects of pump therapy.

Topics: Blood Glucose; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Administration Schedule; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Infusion Systems; Insulin, Isophane; Insulin, Long-Acting

Insulin glargine (LANTUS) is a once-daily basal insulin analog with a smooth 24-h time-action profile that provides effective glycemic control with reduced hypoglycemia risk (particularly nocturnal) compared with NPH insulin in patients with type 2 diabetes. A recent "treat-to-target" study has shown that more patients on insulin glargine reached HbA(1c) levels < or =7.0% without confirmed nocturnal hypoglycemia compared with NPH insulin. We further assessed the risk for hypoglycemia in a meta-analysis of controlled trials of a similar design for insulin glargine versus once- or twice-daily NPH insulin in adults with type 2 diabetes.. All studies were 24-28 weeks long, except one 52-week study, for which interim 20-week data were used.. Patient demographics were similar between the insulin glargine (n = 1,142) and NPH insulin (n = 1,162) groups. The proportion of patients achieving target HbA(1c) (< or =7.0%) was similar between insulin glargine-and NPH insulin-treated patients (30.8 and 32.1%, respectively). There was a consistent significant reduction of hypoglycemia risk associated with insulin glargine, compared with NPH insulin, in terms of overall symptomatic (11%; P = 0.0006) and nocturnal (26%; P < 0.0001) hypoglycemia. Most notably, the risk of severe hypoglycemia and severe nocturnal hypoglycemia were reduced with insulin glargine by 46% (P = 0.0442) and 59% (P = 0.0231), respectively.. These results confirmed that insulin glargine given once daily reduces the risk of hypoglycemia compared with NPH insulin, which can facilitate more aggressive insulin treatment to a HbA(1c) target of < or =7.0% in patients with type 2 diabetes.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

Insulin treated diabetic patients have often to contend with variability in the action of injected insulin and to some unpredictibility in glycemic control. The variability in blood glucose control seems particularly important with long-acting insulins. Insulin detemir belongs to a new class of non-crystalline form of long-acting insulin analogs. Absorption of insulin detemir is dependent on neither appropriate resuspension before injection and dissolution of crystals in the subcutaneous tissue, as is the case for NPH insulin, nor on formation and dissolution of microprecipitates, as is the case for insulin glargine. In euglycemic glucose clamp studies, insulin detemir was associated with significantly less within-subjects variability for the pharmacodynamic endpoints than both NPH insulin and insulin glargine. Three, up to 6 months trials, carried out in patients with type 1 diabetes have shown that the day-to-day within-subject variations in plasma glucose were significantly lower with insulin detemir than with human NPH insulin. Similar results have been reported in patients with type 2 diabetes. Nightly 8-h plasma glucose recordings showed a smoother and more stable profile with insulin detemir than with NPH insulin. In patients with type 1 diabetes the combination of insulin detemir with mealtime insulin aspart, a fast-acting insulin analog, provides a smoother and more stable profile with lower post-prandial plasma glucose levels that the combination of NPH insulin with regular human insulin before each meal. In several trials, the risk of hypoglycemia, particularly of nocturnal hypoglycemia, was significantly lower with insulin detemir than with NPH insulin. In conclusion insulin detemir offers a better reproducibility as compared with other basal insulins, reduces the risk of hypoglycemia, and may lead the patients to titrate their insulin doses more easily and therefore to achieve more often glycemic objectives. The combination of rapid- and long-acting insulin analogs reproduces a more physiological insulin secretion and thereby reduces the risk of hypoglycemia and improves the overall 24-h glycemic profile.

Topics: Blood Glucose; Circadian Rhythm; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Reproducibility of Results

Biphasic insulin aspart 30 (BIAsp 30 [30% soluble, rapid-acting insulin aspart and 70% protamine-bound insulin aspart], NovoLog Mix 70/30, Novo Nordisk, Bagsvaerd, Denmark), a premixed insulin analogue, addresses both the prandial and basal aspects of glucose regulation when used once or twice daily in patients with type 1 or type 2 diabetes. It provides overall glycemic control similar to biphasic human insulin 30 (BHI 30, 30% human insulin and 70% neutral protamine Hagedorn [NPH] insulin) in patients with type 1 or type 2 diabetes.. The aim of this review was to evaluate the safety profile associated with BIAsp 30 in patients with type 1 or type 2 diabetes versus that of comparator insulin products, including BHI 30 and biphasic insulin lispro 25 (Mix 25 [25% biphasic insulin lispro and 75% protaminated lispro], Humalog Mix 75/25, Eli Lilly and Company, Indianapolis, Indiana), together with the basal insulins, including NPH insulin and insulin glargine (Lantus, Sanofi-Aventis Pharmaceuticals, Paris, France).. Data from human clinical studies published in peer-reviewed journals or as conference proceedings that reported safety results in patients with type 1 or type 2 diabetes who were treated with BIAsp 30 versus comparator insulins were evaluated. To locate the appropriate articles, a MEDLINE search was performed for all years up to February 2005, using the following key words: biphasic insulin aspart, BIAsp 30, biphasic insulin, and premixed insulin. Additional papers were identified by examining the reference lists in these papers as well as our own personal reference files. Results from 17 publications were analyzed. The analysis included >2600 patients with type 2 diabetes (mean [range] age, 58 [36-70] years; duration of diabetes, 11.8 [9-17] years; and baseline glycosylated hemoglobin [HbA1c], 8.6% [7.5%-9.9%]). It also included 104 patients with type 1 diabetes (mean [range] age, 44.5 [30-58] years; duration of diabetes, 16 [2-30] years; and baseline HbA1c, 8.4% [7.2%-10.4%]).. Hypoglycemia occurred in 43% to 57% of patients receiving BIAsp 30 versus 32% to 57% of patients receiving BHI 30 and 28% of patients receiving NPH insulin. Major hypoglycemic events were uncommon in most studies; but when they did occur, they were reported less frequently in patients receiving BIAsp 30 (2%-8% of patients) than in patients receiving BHI 30 (2%-14% of patients). Furthermore, patients treated with BIAsp 30 were at lower risk of experiencing minor nocturnal hypoglycemia than patients receiving comparator insulin; in 1 study, the relative risk (BIAsp 30 vs BHI 30) was calculated to be 0.63 (95% CI, 0.37 to 1.09). The adverse event (AE) profile, weight gain during treatment, and formation of cross-reactive antibodies were not different between BIAsp 30 and BHI 30. AEs were reported in 36% to 90% of patients receiving BIAsp 30, 38% to 88% of patients receiving BHI 30, and 51% of patients receiving Mix 25. The use of oral antidiabetic drugs in combination with BIAsp 30 did not alter the safety profile of BIAsp 30.. The flexible and convenient treatment regimen offered by BIAsp 30, together with its ability to improve postprandial glucose control, is associated with a safety profile comparable to that of BHI 30 and NPH insulin, with a lower risk of major and nocturnal hypoglycemic events.

Topics: Adult; Aged; Biphasic Insulins; Clinical Trials as Topic; Cross Reactions; Diabetes Complications; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Randomized Controlled Trials as Topic; Weight Gain

It is estimated that 39% of people with diabetes worldwide who use insulin are prescribed premixes, largely because of the practical advantages of addressing both prandial and basal insulin needs with a single product. Rapid-acting premixed insulin analogues such as biphasic insulin aspart 30 (BIAsp 30 [30% soluble insulin aspart and 70% protamine-crystallized insulin aspart], NovoLog Mix 70/30, Novo Nordisk, Bagsvaerd, Denmark) have been developed recently to overcome the pharmacokinetic limitations of regular human insulin used in the most commonly prescribed premix, biphasic human insulin 30 (BHI 30, 30% human insulin and 70% neutral protamine Hagedorn [NPH] insulin). It would be expected that these pharmacokinetic improvements would enhance clinical performance. However, the efficacy of BIAsp 30 compared with other common treatment regimens has not yet been systematically reviewed.. The aim of this paper is to review current data on the efficacy of BIAsp 30 in comparison with other treatment strategies in type 2 diabetes, including oral antidiabetic drugs (eg, metformin, sulfonylureas, meglitinides, thiazolidinediones), conventional insulins (eg, BHI 30, NPH insulin), and other analogue insulins (eg, insulin glargine, biphasic insulin lispro 25 [Mix 25, 25% biphasic insulin lispro and 75% protaminated lispro]). The focus will be on comparative efficacy (ie, postprandial glucose [PPG], blood glucose profiles, and glycosylated hemoglobin [HbA1c]).. We identified human clinical studies published through February 2005 involving BIAsp 30 in patients with type 2 diabetes by performing a MEDLINE search (key words: biphasic insulin aspart, BIAsp 30, biphasic insulin, and premixed insulin). Additional papers were identified by assessing (1) the reference lists in these studies, (2) published conference proceedings, and (3) our reference files. A total of 21 relevant papers were retrieved: 13 were published as full manuscripts, 1 as a short communication, 5 as abstracts, and 1 as a poster. One paper is currently in press. Novo Nordisk supplied data from an unpublished trial (Study 1536, 2004), as well as data from a trial published in abstract form only (Study 1269, 2002).. A regimen of BIAsp 30 BID, at breakfast and dinner, provides improved PPG control compared with BHI 30 BID, NPH BID, and insulin glargine OD for patients with type 2 diabetes. Fasting plasma glucose (FPG) with BIAsp 30 was not significantly different from FPG with insulin glargine; however, FPG was higher with BIAsp 30 than with NPH. BIAsp 30 prevented excessive PPG excursions whether it was injected at the beginning of a meal or < or =15 minutes after starting a meal. BIAsp 30 was not associated with an increased risk of major hypoglycemia compared with other insulin regimens used in the studies reviewed. The incidence of minor hypoglycemic events with BIAsp 30 varied across studies but occurred with frequency or risk similar to BHI 30, Mix 25, or NPH. Treat-to-target trials reported that BIAsp 30 can be used to intensify insulin therapy and to reach the glycemic target recommended by the American Diabetes Association (ie, HbA1c <7.0%). One study reported a greater lowering of postprandial triglyceride levels with BIAsp 30 than with BHI 30.. BIAsp 30 BID can reduce PPG levels to a greater extent than other common treatment regimens, including basal insulin OD. Using BIAsp 30, even once daily, may allow some patients to reach glycemic targets with a degree of convenience and tolerability that may not be achievable with other treatment regimens.

Topics: Biphasic Insulins; Blood Glucose; Diabetes Complications; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Lipids; Postprandial Period; Randomized Controlled Trials as Topic; Weight Gain

The prescription of insulin glargine has increased in Sweden and during 2003 the cost in the county of Skåne equalled all intermediate-acting insulins (ATC-code A10AC01). To investigate the evidence behind claimed advantages of insulin glargine over existing therapy, we carried out a systematic review. We analysed the available documentation presented after registration of the drug by the drug regulatory authorities FDA and EMEA. Data presented at the authorithies' Internet sites was approached. All published studies not included in the registration file were also included in the analysis. Data on glycemic control, expressed as HbA1c, and hypoglycemia was registered. Most studies included a comparison with NPH insulin, incorporating both type 1 and type 2-diabetes. In six pivotal studies there were no significant difference between the two insulin treatments regarding HbA1c, nor was there any substancial evidence concerning differences regarding hypoglycemia. According to FDA, no claim of superiority of insulin glargine could be expressed as all studies had an open design. Studies not included at registration did not add any new evidence. The claimed advantages of insulin glargine does not seem to be substantiated by available evidence.

Topics: Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Evidence-Based Medicine; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Meta-Analysis as Topic

A better diabetes regulation seems possible, with the aid of the recently available insulin analogs than with isophane insulin, for patients with diabetes mellitus type 1 or 2. The glycaemic regulation can be improved and/or the chances of hypoglycaemia can be reduced by reduced variability in the resorption of (insulin glargine) or by binding to the serum albumin (insulin detemir). With poor regulation it seems possible to bring about a substantial HbA1c reduction without an increase in hypoglycaemic incidents, and with reasonable to good regulation to achieve a reduction of the number of hypoglycaemias whilst HbA1c remains the same.

Topics: Blood Glucose; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

Topics: Adult; Computer Graphics; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Insulin; Insulin, Isophane; Postprandial Period; Practice Guidelines as Topic; Treatment Outcome

Tight glycaemic control (ideally, HbA1c<7%) is central to reducing the risk of long-term complications of diabetes. This approach, for both Type 1 and Type 2 diabetes, commonly involves the use of basal insulin, and must be achieved with minimal risk of hypoglycaemia (particularly nocturnal episodes). Indeed, concern around hypoglycaemia is a major barrier to achieving tight glycaemic control, and is a common problem with those protracted-acting insulins most frequently used in clinical practice for basal insulin supply. Other drawbacks include inter- and intra-patient variability that compromises dosing reproducibility and unsuitability for single daily dosing. New long-acting human insulin analogues with action profiles designed to overcome these problems are now available in clinical practice or are under evaluation in clinical trials. Clinical evidence suggests efficacy and safety advantages for these analogues over NPH insulin (the most commonly used basal insulin), and may bring closer the goal of tight glycaemic control in patients with diabetes.

Topics: Carrier Proteins; Delayed-Action Preparations; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Administration Schedule; Humans; Hypoglycemia; Hypoglycemic Agents; Infusions, Parenteral; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

Insulin aspart (NovoLog, NovoRapid), a rapid-acting human insulin analog, provides more rapid absorption than regular human insulin after subcutaneous administration. In most randomized, nonblind clinical trials in patients with type 1 diabetes mellitus, insulin aspart administered immediately before meals resulted in significantly lower mean glycosylated hemoglobin (HbA1c) levels than regular human insulin (usually administered 30 minutes before a meal). Insulin aspart also significantly improved postprandial glycemic control compared with regular human insulin. The efficacy of insulin aspart was similar to that of insulin lispro when administered to patients with type 1 diabetes mellitus via continuous subcutaneous infusion in a randomized, nonblind trial. Preliminary data from randomized, nonblind trials suggest insulin aspart had a trend towards lower HbA1c levels compared with regular human insulin in patients with type 2,diabetes mellitus. Biphasic insulin aspart (30% soluble [rapid-acting] and 70% protamine-bound insulin aspart [BIAsp30]) [NovoLog Mix 70/30, NovoMix 30(2)] generally provided significantly better postprandial glucose control than a similar mixture of biphasic regular human insulin (BHI30) in a randomized, nonblind trial in patients with type 1 or 2 diabetes mellitus. However, the long-term efficacy of BIAsp30 was similar to that of BHI30 after 2 years in a randomized, nonblind trial in patients with type 2 diabetes mellitus. Patients with type 1 or 2 diabetes mellitus reported greater treatment satisfaction with insulin aspart or BIAsp30 than with regular human insulin or BHI30. The overall incidence of hypoglycemia with insulin aspart was lower than, or similar to, that of regular human insulin. Moreover, insulin aspart tended to be associated with a lower occurrence of nocturnal hypoglycemia and severe hypoglycemic events than regular human insulin.. The standard preparation of insulin aspart has the potential to better mimic the physiological response to meals than regular human insulin. Insulin aspart when combined with a suitable basal insulin improved overall glycemic control and led to a similar or lower number of hypoglycemic episodes compared with a similar regular human insulin regimen. Insulin aspart was generally as effective and well tolerated as insulin lispro when administered by continuous subcutaneous infusion in a single comparative trial. The efficacy of biphasic insulin aspart has been documented in a small number of trials. Both insulin aspart and biphasic insulin aspart provide for flexible and convenient administration. Insulin aspart is now well established as an effective and convenient means of providing glycemic control which offers clinical and practical advantages over regular human insulin.

Topics: Biphasic Insulins; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Insulin; Insulin Aspart; Insulin, Isophane; Randomized Controlled Trials as Topic; Treatment Outcome

Insulin aspart, a rapid-acting human insulin analogue, provides more rapid absorption than regular human insulin after subcutaneous administration. In most randomised, nonblind clinical trials in patients with type 1 diabetes mellitus, insulin aspart administered immediately before meals resulted in significantly lower mean glycosylated haemoglobin A(1c ) (HbA(1c)) levels than regular human insulin (usually administered 30 minutes before a meal). Insulin aspart also significantly improved postprandial glycaemic control compared with regular human insulin. The efficacy of insulin aspart was similar to that of insulin lispro when administered to patients with type 1 diabetes mellitus via continuous subcutaneous infusion in a randomised, nonblind trial. Preliminary data from randomised, nonblind trials suggest insulin aspart had a trend towards lower HbA(1c) levels compared with regular human insulin in patients with type 2 diabetes mellitus. Biphasic insulin aspart [30% soluble (rapid-acting) and 70% protamine-bound insulin aspart (BIAsp30)] generally provided significantly better postprandial glucose control than a similar mixture of biphasic regular human insulin (BHI30) in a randomised, nonblind trial in patients with type 1 or 2 diabetes mellitus. However, the long-term efficacy of BIAsp30 was similar to that of BHI30 after 2 years in a randomised, nonblind trial in patients with type 2 diabetes mellitus. Patients with type 1 or 2 diabetes mellitus reported greater treatment satisfaction with insulin aspart or BIAsp30 than with regular human insulin or BHI30. The overall incidence of hypoglycaemia with insulin aspart was lower than, or similar to, that of regular human insulin. Moreover, insulin aspart tended to be associated with a lower occurrence of nocturnal hypoglycaemia and severe hypoglycaemic events than regular human insulin.. The standard preparation of insulin aspart has the potential to better mimic the physiological response to meals than regular human insulin. Insulin aspart when combined with a suitable basal insulin improved overall glycaemic control and led to a similar or lower number of hypoglycaemic episodes compared with a similar regular human insulin regimen. Insulin aspart was generally as effective and well tolerated as insulin lispro when administered by continuous subcutaneous infusion in a single comparative trial. The efficacy of biphasic insulin aspart has been documented in a small number of trials. Both insulin aspart and biphasic insulin aspart provide for flexible and convenient administration. Insulin aspart is now well established as an effective and convenient means of providing glycaemic control which offers clinical and practical advantages over regular human insulin.

Topics: Absorption; Adolescent; Adult; Biphasic Insulins; Child; Databases, Bibliographic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Lispro; Insulin, Isophane; Patient Satisfaction; Quality of Life; Randomized Controlled Trials as Topic

Topics: Carbamates; Chromans; Diabetes Mellitus, Type 2; Drug Synergism; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Insulin, Isophane; Metformin; Piperidines; Thiazoles; Thiazolidinediones; Troglitazone

Tight control can prevent complications in type 2 diabetes, and many patients will require insulin therapy to achieve this. Newer insulin formulations may offer some advantages with regard to patient convenience and a reduction in hypoglycaemia.

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Middle Aged; Prospective Studies

Insulin lispro is an analog of human insulin created when the amino acids at positions 28 and 29 of the B-chain of insulin are reversed. The natural sequence in human insulin at these positions is proline at B28 and lysine at B29. At physiologic concentrations, insulin lispro exists in solution as a monomer. As such, it's rate of absorption from subcutaneous sites of injection is greater that of regular insulin. The pharmacokinetic and pharmacodynamic profiles of insulin lispro indicate that it is more rapid-acting, and therefore a more physiological mealtime insulin than regular insulin. In addition, it shows a shorter duration of activity, approximately up to 5 hours. Insulin lispro given 0 to 15 minutes before the meal translate into better glycemic control and less hypoglycemia risk in clinical studies either in type 1 or type 2 diabetes when compare with regular human insulin given 30-45 minutes before meals.

Topics: Adult; Clinical Trials as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Lispro; Insulin, Isophane; Male; Middle Aged; Multicenter Studies as Topic; Time Factors

Premix insulin is commonly used in some regions of the world, despite the higher risk of hypoglycaemia and weight gain compared with basal insulin, based on the premise that it offers a simplified insulin regimen. iGlarLixi is a once-daily titratable fixed-ratio formulation that combines basal insulin glargine 100 units/mL (iGlar) and the GLP-1 RA, lixisenatide, which offers a single-injection option for treatment intensification, with improved HbA1c reductions, similar hypoglycaemia risk and more favourable bodyweight profiles over iGlar alone. This randomized controlled study directly compares, for the first time, treatment intensification with iGlarLixi versus premix insulin analogue biphasic insulin aspart 30 (BIAsp 30) in adults with T2D inadequately controlled on basal insulin in combination with one or two oral antihyperglycaemic drugs.. This was an open-label, active-controlled, comparative, parallel-group, multicentre, phase 3b study. In total, 887 adults with T2D uncontrolled on basal insulin were randomized to switch to either iGlarLixi once daily, or BIAsp 30 twice daily, for 26 weeks.. Overall, 887 participants were enrolled (mean age 59.8 years, 50.2% female) from 89 centres in 17 countries. At baseline, 65.6% had a duration of T2D of 10 years or longer, and the mean HbA1c at baseline was 8.6%.. The study directly compared the efficacy and safety of iGlarLixi versus BIAsp 30 in people with T2D uncontrolled on basal insulin and one or more oral antihyperglycaemic agents. These results provide robust clinical data that may inform clinicians in their therapeutic management of people with T2D uncontrolled on basal insulin requiring additional therapy.

Topics: Adult; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Drug Combinations; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Aspart; Insulin Glargine; Insulin, Isophane; Male; Middle Aged

Insulin detemir, being used increasingly during pregnancy, may have pharmacologic benefits compared with neutral protamine Hagedorn.. We evaluated the probability that compared with treatment with neutral protamine Hagedorn, treatment with insulin detemir reduces the risk for adverse neonatal outcome among individuals with type 2 or overt type 2 diabetes mellitus (gestational diabetes mellitus diagnosed at <20 weeks' gestation).. We performed a multiclinic randomized controlled trial (September 2018 to January 2020), which included women with singleton gestation with type 2 or overt type 2 diabetes mellitus who sought obstetrical care at ≤21 weeks' gestation. Participants were randomized to receive either insulin detemir or neutral protamine Hagedorn by a clinic-stratified scheme. The primary outcome was a composite of adverse neonatal outcomes, including shoulder dystocia, large for gestational age, neonatal intensive care unit admission, respiratory distress (defined as the need of at least 4 hours of respiratory support with supplemental oxygen, continuous positive airway pressure or ventilation at the first 24 hours of life), or hypoglycemia. The secondary neonatal outcomes included gestational age at delivery, small for gestational age, 5-minute Apgar score of <7, lowest glucose level, need for intravenous glucose, respiratory distress syndrome, need for mechanical ventilation or continuous positive airway pressure, neonatal jaundice requiring therapy, brachial plexus injury, and hospital length of stay. The secondary maternal outcomes included hypoglycemic events, hospital admission for glucose control, hypertensive disorder of pregnancy, maternal weight gain, cesarean delivery, and postpartum complications. We used the Bayesian statistics to estimate a sample size of 108 to have >75% probability of any reduction in the primary outcome, assuming 80% power and a hypothesized effect of 33% reduction with insulin detemir. All analyses were intent to treat under a Bayesian framework with neutral priors (a priori assumed a 50:50 likelihood of either intervention being better; National Clinical Trial identifier 03620890).. There were 108 women randomized in this trial (57 in insulin detemir and 51 in neutral protamine Hagedorn), and 103 women were available for analysis of the primary outcome (n=5 for pregnancy loss before 24 weeks' gestation). Bayesian analysis indicated an 87% posterior probability of reduced primary outcome with insulin detemir compared with neutral protamine Hagedorn (posterior adjusted relative risk, 0.88; 95% credible interval, 0.61-1.12). Bayesian analyses for secondary outcomes showed consistent findings of lower adverse maternal outcomes with the use of insulin detemir vs neutral protamine Hagedorn: for example, maternal hypoglycemic events (97% probability of benefit; posterior adjusted relative risk, 0.59; 95% credible interval, 0.29-1.08) and hypertensive disorders (88% probability of benefit; posterior adjusted relative risk, 0.81; 95% credible interval, 0.54-1.16).. In our comparative effectiveness trial involving individuals with type 2 or overt type 2 diabetes mellitus, use of insulin detemir resulted in lower rates of adverse neonatal and maternal outcomes compared with neutral protamine Hagedorn.

Topics: Abortion, Spontaneous; Adult; Diabetes Mellitus, Type 2; Female; Fetal Macrosomia; Gestational Age; Humans; Hypoglycemia; Infant, Newborn; Insulin Detemir; Insulin, Isophane; Intensive Care, Neonatal; Pregnancy; Pregnancy Complications; Pregnancy in Diabetics; Pregnancy Outcome; Respiratory Distress Syndrome, Newborn; Shoulder Dystocia

To observe whether there are sexual-related differences in response to mid- or low-premixed insulin in type 2 diabetic patients.. This was an analysis of CGM data of a previous study. After screening, patients with longstanding T2D receive a 7-day continuous subcutaneous insulin infusion (CSII) therapy, and then subjects were randomly assigned 1 : 1 into two groups receiving Novo Mix 30 or Humalog Mix 50 regimen for a 2-day phage, followed by a 4-day cross-over period. A 4-day continuous glucose monitoring (CGM) was performed during the cross-over period. The primary endpoint was the differences in glycemic control between male and female patients receiving mid- or low-premixed insulin therapy.. A total of 102 patients (52 men and 50 women) completed the study. Our data showed that male patients had significant decrease in mean glucose levels monitored by CGM after three meals during Humalog Mix 50 treatment period compared to those received Novo Mix 30 regimen (0900: 11.0 ± 2.5 vs. 12.2 ± 2.8, 1000: 9.9 ± 2.9 vs. 11.3 ± 3.1, 1200: 8.0 ± 1.9 vs. 9.1 ± 2.5, 1400: 9.2 ± 2.3 vs. 10.3 ± 2.5, and 2000: 7.3 ± 2.1 vs. 8.2 ± 2.4 mmol/L,. Our data indicate that male patients with T2D receiving mid-premixed insulin analogue regimen may have a potential benefit of improvement in glycemic control compared to female patients. This trial is registered with ClinicalTrials.gov ChiCTR-IPR-15007340.

Topics: Aged; Biphasic Insulins; Blood Glucose; Blood Glucose Self-Monitoring; Cross-Over Studies; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin Infusion Systems; Insulin Lispro; Insulin, Isophane; Male; Middle Aged; Monitoring, Ambulatory; Sex Factors; Treatment Outcome

To evaluate the efficacy and safety of thrice daily Biphasic Human Insulin 30 (BHI 30) versus the traditional twice-daily regimen in type 2 diabetes mellitus (T2DM) patients. It's a cross over single clinical study. Twenty-two diabetic patients who were already using BHI 30 in twice or thrice daily regimens with or without metformin were included. At the 1st interval; patients continued on their usual insulin regimen as twice or thrice daily injections with adjustment of insulin doses guided by their glucose readings. On the 2nd interval; patients were switched to the other regimen with the same total daily insulin dose redistributed.. There was a significant decrease in HbA1c level (p < 0.05) at the end of the first 3 months of trial regardless on which regimen the patient started, but there was no significant difference in the mean HbA1c reduction in patients when they were on twice daily insulin injections (1.1 ± 1.3) versus the time they were on thrice daily insulin injections (0.8 ± 1.71), p > 0.05. On the other hand, patients had lower average blood glucose readings (mg/dl) when they were on thrice daily insulin injections (161.4 ± 62.7) compared to twice daily regimen (166.0 ± 69.5), p < 0.05.

Topics: Adult; Aged; Biphasic Insulins; Cross-Over Studies; Diabetes Mellitus, Type 2; Drug Combinations; Female; Glycated Hemoglobin; Humans; Injections; Insulin; Insulin, Isophane; Male; Metformin; Middle Aged

A well-known metabolic side effect from treatment with glucocorticoids is glucocorticoid-induced diabetes mellitus (GIDM). Guidelines on the management of GIDM in hospitalized patients (in the non-critical care setting), recommend initiation of insulin therapy. The scientific basis and evidence for superiority of insulin therapy over other glucose lowering therapies is however poor and associated with episodes of both hypo- and hyperglycaemia. There is an unmet need for an easier, safe and convenient therapy for glucocorticoid-induced diabetes.. EANITIATE is a Danish, open, prospective, multicenter, randomized (1:1), parallel group study in patients with new-onset diabetes following treatment with glucocorticoids (> 20 mg equivalent prednisolone dose/day) with blinded endpoint evaluation (PROBE design). Included patients are randomized to either a Sodium-Glucose-Cotransporter 2 (SGLT2) inhibitor or neutral protamin Hagedorn (NPH) insulin and followed for 30 days. Blinded continuous glucose monitoring (CGM) will provide data for the primary endpoint (mean daily blood glucose) and on glucose fluctuations in the two treatment arms. Secondary endpoints are patient related outcomes, hypoglycaemia, means and measures of variation for all values and for time specific glucose values. This is a non-inferiority study with the intent to demonstrate that treatment with empagliflozin is not inferior to treatment with NPH insulin when it comes to glycemic control and side effects.. This novel approach to management of glucocorticoid-induced hyperglycemia has not been tested before and if SGLT2 inhibition with empaglifozin compared to NPH-insulin is a safe, effective and resource sparing treatment for GIDM, it has the potential to improve the situation for affected patients and have health economic benefits.. www.clinicaltrialsregister.eu no.: 2018-002640-82. Prospectively registered November 20th. 2018. Date of first patient enrolled: June 4th. 2019. This protocol article is based on the EANITATE protocol version 1.3, dated 29. January 2018.

Topics: Benzhydryl Compounds; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Equivalence Trials as Topic; Glucocorticoids; Glucosides; Glycemic Control; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin, Isophane; Monitoring, Physiologic; Multicenter Studies as Topic; Patient Reported Outcome Measures; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2 Inhibitors; Treatment Outcome

In China, most normal BMI (body mass index of ≥18.5 to <25 kg/m

Topics: Adiposity; Adult; Aged; Biphasic Insulins; Body Fat Distribution; Body Mass Index; Diabetes Mellitus, Type 2; Exenatide; Female; Humans; Insulin Lispro; Insulin Resistance; Insulin-Secreting Cells; Insulin, Isophane; Intra-Abdominal Fat; Male; Middle Aged; Obesity, Abdominal; Treatment Outcome

To assess the efficacy and safety of twice-daily insulin degludec/insulin aspart (IDegAsp) versus biphasic insulin aspart 30 (BIAsp 30) twice daily, both ± metformin, in Chinese adults (N = 543) with type 2 diabetes (T2D) inadequately controlled on premixed/self-mixed or basal insulin ± metformin.. We conducted a 26-week, phase III, open-label, treat-to-target, 2:1 randomized trial. Hierarchical testing was used with non-inferiority of glycated haemoglobin (HbA1c) change from baseline to week 26 as the primary endpoint and superiority for the confirmatory secondary endpoints which were as follows: change from baseline in fasting plasma glucose (FPG); nocturnal confirmed hypoglycaemic episodes (12:01-5:59 am, inclusive); total confirmed hypoglycaemic episodes (severe or plasma glucose <3.1 mmol/L with/without symptoms); body weight; and percentage of responders (HbA1c <53 mmol/mol [<7.0%]) without confirmed hypoglycaemic episodes.. Non-inferiority for change from baseline to week 26 in HbA1c and superiority of IDegAsp twice daily versus BIAsp 30 twice daily for change in FPG, nocturnal confirmed and total confirmed hypoglycaemic episodes, was demonstrated. Estimated rates of nocturnal confirmed and total confirmed hypoglycaemic episodes were 47% and 43% lower, respectively, with IDegAsp twice daily versus BIAsp 30 twice daily. Superiority for change in body weight was not confirmed. Participants were more likely to reach the HbA1c goal of <53 mmol/mol (<7.0%) without confirmed hypoglycaemia with IDegAsp twice daily versus BIAsp 30 twice daily by trial end. No new safety signals were identified.. The efficacy and safety of IDegAsp in Chinese patients with T2D was demonstrated, confirming results from international trials.

Topics: Aged; Biphasic Insulins; Blood Glucose; Body Weight; China; Diabetes Mellitus, Type 2; Drug Combinations; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged

To compare the efficacy and safety of biphasic insulin aspart 30 (BIAsp 30) administered three times daily (TID) vs. twice daily (BID), plus metformin, in patients with type 2 diabetes mellitus (T2DM) inadequately controlled on basal insulin ± 1 oral antidiabetic drug (OAD).. Randomised, multinational, open-label, treat-to-target trial. Subjects inadequately controlled (HbA1c 7.5-10.0%) on basal insulin and metformin ± 1 OAD were randomised to BIAsp30 TID (n = 220) or BIAsp30 BID (n = 217). Primary endpoint was change from baseline in HbA1c after 24 weeks of treatment.. BIAsp 30 administered either TID or BID with metformin was a safe and effective option when intensifying treatment after failure of basal insulin and OADs in patients with T2DM. Adding a third injection at lunchtime may be preferable if HbA1c remains above target, if the lunchtime meal is the largest meal of the day, or if persistent postprandial hyperglycaemia after lunch is observed.. ClinicalTrials.gov, NCT02582242.

Topics: Administration, Oral; Adolescent; Adult; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; International Agencies; Male; Middle Aged; Treatment Outcome; Young Adult

To confirm non-inferiority of biphasic insulin aspart 30 (BIAsp 30) plus metformin to BIAsp 30 in lowering glycated haemoglobin (HbA1c) in Chinese patients with inadequately controlled type 2 diabetes using oral antidiabetic drugs.. In this 16-week, prospective, randomized, open-label, multicentre, parallel-controlled study, patients aged 18-79 years with HbA1c ≥7% were randomized to BIAsp 30 plus metformin (n = 130) or BIAsp 30 (n = 127). Initially, 500 mg metformin was administered twice daily and BIAsp 30 was administered at 0.2-0.3 U/kg/d. Changes in HbA1c % from baseline to week 16 as well as secondary and safety endpoints were assessed.. In total, 83.66% of patients in the BIAsp 30 plus metformin (n = 110) and the BIAsp 30 (n = 105) groups completed the study. Mean (±standard deviation) change in HbA1c from baseline to endpoint was -1.74 ± 1.64% and -1.32 ± 2.05% with BIAsp 30 plus metformin and BIAsp 30, respectively. Least squares mean treatment difference was -0.67% (95% CI, -1.06; -0.28). The upper limit of the 95% CI was <0.4 (non-inferiority margin). A significantly higher proportion of individuals reached HbA1c <7% with BIAsp 30 plus metformin than with BIAsp 30 (53.15% vs 35.19%; P = 0.0074). At endpoint, daily BIAsp 30 dose (P < 0.001) and weight gain were significantly lower (P < 0.05) in the BIAsp 30 plus metformin group compared with the BIAsp 30 group. No between-group differences in number of hypoglycaemic events were observed.. BIAsp 30 plus metformin was non-inferior to BIAsp 30 in safely reducing HbA1c in this study.

Topics: Aged; Biphasic Insulins; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Male; Metformin; Middle Aged; Prospective Studies; Treatment Outcome; Weight Gain

No safety issues were revealed with either basal insulin. Due to the low number of patients recruited, no efficacy conclusions could be drawn. ClinicalTrials.gov identifier: NCT02131272. What is known: • There is a growing worldwide epidemic of type 2 diabetes in children and adolescents. • There is a lack of research and limited treatment options currently available in this population. What is new: • No safety issues with insulin detemir or neutral protamine Hagedorn insulin in children and adolescents with type 2 diabetes were observed. • Improving clinical trial recruitment, along with providing early, efficacious, and safe treatment options, in this population is critical.

Topics: Adolescent; Blood Glucose; Child; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin, Isophane; Life Style; Male; Metformin

In Japan, premixed insulins are commonly used as starter insulin for type 2 diabetes. This subpopulation analysis assessed the efficacy and safety of twice-daily LM25 (25% insulin lispro/75% insulin lispro protamine) and LM50 (50% insulin lispro/50% insulin lispro protamine) as starter insulin in Japanese subjects, and compared these results with the whole-trial populations of East Asian subjects. In this subpopulation analysis of an open-label, phase 4, randomized trial (CLASSIFY), Japanese subjects received LM25 (n = 88) or LM50 (n = 84) twice-daily for 26 weeks. The primary outcome was change from baseline at Week 26 in glycated hemoglobin (HbA1c). Results for Japanese subjects were generally similar to those for the whole-trial population. Similar changes from baseline in HbA1c were observed for LM25 and LM50 groups (least squares [LS] mean difference [95% confidence interval] of LM25 - LM50 = 0.13 [-0.16, 0.41]%, 1.42 [-1.75, 4.48] mmol/mol, p = 0.388). More LM50-treated subjects than LM25-treated subjects achieved HbA1c targets of <7.0% (59.5% versus 43.2%; p = 0.034) or ≤6.5% (45.2% versus 28.4%; p = 0.027). The reduction in postprandial blood glucose concentrations after morning and evening meals was statistically significantly greater for LM50 than for LM25. The incidence of both hypoglycemia and treatment-emergent adverse events were similar between treatment groups. Both LM25 and LM50 twice daily appear to be effective and well tolerated as starter insulin, although LM50 might be more effective for Japanese type 2 diabetes patients.

Topics: Aged; Asia, Eastern; Asian People; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Lispro; Insulin Resistance; Insulin, Isophane; Japan; Male; Middle Aged; Postprandial Period

The present study was a subgroup analysis of a Pan-Asian Phase 3 open-label randomized treat-to-target trial evaluating insulin degludec/insulin aspart (IDegAsp) and biphasic insulin aspart 30 (BIAsp 30) in Japanese subjects with type 2 diabetes inadequately controlled on insulin.. Eligible subjects (n = 178) were randomized (2: 1) to twice-daily (b.i.d.) IDegAsp or BIAsp 30 with or without metformin for 26 weeks, titrated to a blood glucose target of between 3.9 and <5.0 mmol/L. Changes in HbA. The results indicate that IDegAsp b.i.d. improves glycemic control and, compared with BIAsp 30, lowers the rate of nocturnal confirmed hypoglycemia.

Topics: Aged; Asian People; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypertension; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Insulin, Long-Acting; Male; Metformin; Middle Aged; Nasopharyngitis; Treatment Outcome

To evaluate the efficacy and safety of twice-daily insulin degludec/insulin aspart vs. twice-daily biphasic insulin aspart 30 in people with Type 2 diabetes mellitus who were naïve to insulin.. In this 26-week, multinational, open-label, controlled, two-arm, parallel-group, treat-to-target trial, participants [mean (± sd) age 58.9 (±8.9) years, duration of diabetes 9.5 (±5.9) years, HbA1c 68 (±8.7) mmol/mol or 8.4 (±0.8)% and BMI 31.2 (±4.2) kg/m(2) ) were randomized (1:1) to insulin degludec/insulin aspart (n = 197) or biphasic insulin aspart 30 (n = 197), administered with breakfast and the main evening meal, titrated to a self-monitored plasma glucose target > 3.9 and ≤ 5.0 mmol/l.. The mean HbA1c was reduced to 49 mmol/mol (6.6%) with insulin degludec/insulin aspart and 48 mmol/mol (6.5%) with biphasic insulin aspart 30. Insulin degludec/insulin aspart achieved the prespecified non-inferiority margin (estimated treatment difference 0.02%; 95% CI -0.12, 0.17). Insulin degludec/insulin aspart was superior in lowering fasting plasma glucose (estimated treatment difference -1.00 mmol/l; 95% CI -1.4, -0.6; P < 0.001) and reducing overall and nocturnal confirmed hypoglycaemia at a similar overall insulin dose compared with biphasic insulin aspart 30. Similar proportions of participants in each arm experienced severe hypoglycaemia. Adverse events were equally distributed.. Consistent with previous findings, insulin degludec/insulin aspart twice daily effectively improved long-term glycaemic control, with superior reductions in FPG, and significantly less overall and nocturnal confirmed hypoglycaemia compared with biphasic insulin aspart 30 in people with Type 2 diabetes who were insulin-naïve.

Topics: Aged; Biphasic Insulins; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Combinations; Drug Monitoring; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Insulin, Long-Acting; Male; Meals; Middle Aged; Risk; Severity of Illness Index; Solubility

The present study was to compare the efficacy and safety of subject-driven and investigator-driven titration of biphasic insulin aspart 30 (BIAsp 30) twice daily (BID).. In this 20-week, randomized, open-label, two-group parallel, multicenter trial, Chinese patients with type 2 diabetes inadequately controlled by premixed/self-mixed human insulin were randomized 1:1 to subject-driven or investigator-driven titration of BIAsp 30 BID, in combination with metformin and/or α-glucosidase inhibitors. Dose adjustment was decided by patients in the subject-driven group after training, and by investigators in the investigator-driven group.. Eligible adults (n = 344) were randomized in the study. The estimated glycated hemoglobin (HbA1c) reduction was 14.5 mmol/mol (1.33%) in the subject-driven group and 14.3 mmol/mol (1.31%) in the investigator-driven group. Non-inferiority of subject-titration vs investigator-titration in reducing HbA1c was confirmed, with estimated treatment difference -0.26 mmol/mol (95% confidence interval -2.05, 1.53) (-0.02%, 95% confidence interval -0.19, 0.14). Fasting plasma glucose, postprandial glucose increment and self-measured plasma glucose were improved in both groups without statistically significant differences. One severe hypoglycemic event was experienced by one subject in each group. A similar rate of nocturnal hypoglycemia (events/patient-year) was reported in the subject-driven (1.10) and investigator-driven (1.32) groups. There were 64.5 and 58.1% patients achieving HbA1c <53.0 mmol/mol (7.0%), and 51.2 and 45.9% patients achieving the HbA1c target without confirmed hypoglycemia throughout the trial in the subject-driven and investigator-driven groups, respectively.. Subject-titration of BIAsp 30 BID was as efficacious and well-tolerated as investigator-titration. The present study supported patients to self-titrate BIAsp 30 BID under physicians' supervision.

Topics: Adult; Asian People; Biphasic Insulins; Blood Glucose; China; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Humans; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Insulin, Regular, Human; Male; Middle Aged; Research Personnel; Research Subjects

To compare blood glucose fluctuations in type 2 diabetes mellitus (T2DM) patients were treated using three procedures: insulin intensive therapy which is continuous subcutaneous insulin infusion (CSII), MDI3 (three injections daily), and MDI4 (four injections daily). T2DM patients were hospitalized and were randomly assigned to CSII, aspart 30-based MDI3, and glargine based MDI4. Treatments were maintained for 2-3 weeks after the glycaemic target was reached. After completing the baseline assessment, 6-day continuous glucose monitoring (CGM) was performed before and after completion of insulin treatment. Treatment with CSII provided a greater improvement of blood glucose fluctuations than MDI (MDI3 or MDI4) therapy either in newly diagnosed or in long-standing T2DM patients. In long-standing diabetes patients, the MDI4 treatment group had significantly greater improvement of mean amplitude glycemic excursion (MAGE) than the MDI3 treatment group. However, in patients with newly diagnosed diabetes, there were no significant differences in the improvement of MAGE between MDI3 and MDI4 groups. Glargine based MDI4 therapy provided better glucose fluctuations than aspart 30-based MDI3 therapy, especially in long-standing T2DM patients, if CSII therapy was not available.

Topics: Adult; Aged; Biomarkers; Biphasic Insulins; Blood Glucose; China; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Hospitalization; Humans; Hypoglycemic Agents; Infusions, Subcutaneous; Injections, Subcutaneous; Insulin Aspart; Insulin Glargine; Insulin Infusion Systems; Insulin, Isophane; Male; Middle Aged; Pilot Projects; Prospective Studies; Time Factors; Treatment Outcome

Apart from the mean level of glycemic control, the extent of glucose excursions is another important issue to consider in type 2 diabetes mellitus (T2DM) management. Studies have showed that fluctuations of glucose seem to have more deleterious effects than sustained hyperglycemia in the development of diabetic complications as acute glucose swings activate the oxidative stress. However, until now, no randomized controlled trials have been conducted with the primary aim to evaluate glycemic fluctuation in the comparison between twice-daily exenatide and other treatment paradigms (for example, biphasic insulin aspart 30).. This multicenter, open-label, randomized, parallel trial includes a 1-week screening period and a 16-week treatment period. After the screening period, 150 patients with confirmed type 2 diabetes who are treated with stable, maximum-tolerated doses of metformin will be randomly assigned to one of two groups for antihyperglycemic therapies: exenatide and biphasic insulin aspart 30. The treatment with exenatide will be initiated at a low dose of 5 μg twice a day for 4 weeks and then titrated up to a standard dose of 10 ug twice a day until the completion of the study. The adjustment of insulin dose is instructed to achieve an optimal balance between glycemic control and the risk of hypoglycemia as dictated by clinical practice. The primary outcome is the absolute change of mean amplitude of glycemic excursion from baseline to week 16, which is calculated based on a real-time continuous glucose monitoring system (CGMS).. This is the first randomized controlled trial using a CGMS to evaluate glycemic fluctuation between twice-daily exenatide and insulin aspart 30, which will provide beneficial evidence of exenatide usage in patients with T2DM.. NCT02449603 . Date of registration: 11 May 2015.

Topics: Adolescent; Adult; Aged; Biomarkers; Biphasic Insulins; Blood Glucose; China; Clinical Protocols; Diabetes Mellitus, Type 2; Exenatide; Female; Humans; Hypoglycemic Agents; Incretins; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Peptides; Pilot Projects; Research Design; Time Factors; Treatment Outcome; Venoms; Young Adult

The aim of this study was to compare the efficacy, safety, costs, and cost-effectiveness of biphasic insulin aspart 30 (BIAsp 30) with NPH plus regular human insulin (NPH/Reg) in patients with type 2 diabetes mellitus (T2DM).. It was a Single-center, parallel-group, randomized, clinical trial (Trial Registration: NCT01889095). One hundred and seventy four T2DM patients with poorly controlled diabetes (HbA1c ≥ 8 % (63.9 mmol/mol)) were randomly assigned to trial arms (BIAsp 30 and NPH/Reg) and were followed up for 48 weeks. BIAsp 30 was started at an initial dose of 0.2-0.6 IU/Kg in two divided doses and was titrated according to the glycemic status of the patient. Similarly, NPH/Reg insulin was initiated at a dose of 0.2-0.6 IU/Kg with a 2:1 ratio and was subsequently titrated. Level of glycemic control, hypoglycemic events, direct and indirect costs, quality adjusted life year (QALY) and incremental cost-effectiveness ratio have been assessed.. HbA1c, Fasting plasma glucose (FPG), and two-hour post-prandial glucose (PPG) were improved in both groups during the study (P < 0.05 for all analyses). Lower frequencies of minor, major, and nocturnal hypoglycemic episodes were observed with BIAsp 30 (P < 0.05). Additionally, BIAsp 30 was associated with less weight gain and also higher QALYs (P < 0.05). Total medical and non-medical costs were significantly lower with BIAsp 30 as compared with NPH/Reg (930.55 ± 81.43 USD vs. 1101.24 ± 165.49 USD, P = 0.004). Moreover, BIAsp 30 showed lower ICER as a dominant alternative.. Despite being more expensive, BIAsp 30 offers the same glycemic control as to NPH/Reg dose-dependently and also appears to cause fewer hypoglycemic events and to be more cost-effective in Iranian patients with type 2 diabetes.

Topics: Biphasic Insulins; Blood Glucose; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Drug Costs; Glycated Hemoglobin; Hypoglycemia; Insulin Aspart; Insulin, Isophane

Basal insulin peglispro (BIL) is a novel basal insulin with hepato-preferential action resulting from reduced peripheral effects. This report provides an integrated summary of lipid changes at 26 weeks with BIL and comparator insulins (glargine, NPH) from phase III studies in type 1 diabetes (T1D), insulin-naïve patients with type 2 diabetes (T2D), patients with T2D on basal insulin only and patients with T2D on basal-bolus therapy. BIL treatment had little effect on HDL cholesterol and LDL cholesterol in all patients. The effect of both BIL and glargine treatment on triglycerides (TG) depended on whether patients had been previously treated with insulin. When BIL replaced conventional insulin glargine or NPH treatments, increases in TG levels were observed. When BIL or comparator insulins were given for 26 weeks to insulin-naïve patients with T2D, TG levels were unchanged from baseline with BIL but decreased with either glargine or NPH. The decreased peripheral action of BIL may reduce suppression of lipolysis in peripheral adipose tissue resulting in increased free fatty acid delivery to the liver and, hence, increased hepatic TG synthesis and secretion.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin Lispro; Insulin, Isophane; Lipid Metabolism; Lipids; Male; Middle Aged; Polyethylene Glycols; Retrospective Studies; Triglycerides

Basal insulin peglispro (BIL) has a longer duration of action than conventional insulin analogues and a hepato-preferential mechanism of action. This study assessed whether BIL was non-inferior to isophane insulin (NPH) in reducing HbA1c in insulin-naïve patients with type 2 diabetes, when added to pre-study oral anti-hyperglycaemic medications.. This was a Phase 3, open-label, treat-to-target (TTT), randomized trial with a 2-week lead-in, 26-week treatment and a 4-week safety follow-up period. Patients were randomized to bedtime (pm) NPH, morning (am) BIL or pm BIL in a 1:1:1 ratio.. Six hundred and forty-one patients [NPH, n = 213; BIL, n = 428 (am, n = 213; pm, n = 215)] received study drug. BIL was non-inferior to NPH for HbA1c change from baseline at Week 26 with a between-treatment difference (95% confidence interval) of -0.37% (-0.50, -0.23%). HbA1c at baseline was 8.5%, and was lower in BIL- vs NPH-treated patients after 26 weeks of treatment (6.8% vs 7.1%; P < .001). More BIL-treated patients achieved HbA1c <7.0% and HbA1c <7.0% without nocturnal hypoglycaemia. Fasting serum glucose levels and nocturnal hypoglycaemia rates were lower in BIL-treated patients; total hypoglycaemia rates were similar. Treatment-emergent adverse events were similar between groups. Fasting triglycerides decreased from baseline in both groups and to a greater extent with NPH, but were not significantly different between groups at Week 26. Mean alanine aminotransferase (ALT) increased with BIL treatment, but there was no evidence of acute severe hepatotoxicity.. In this TTT study, BIL treatment showed clinically relevant improvements in glycaemic control and a significant reduction in nocturnal hypoglycaemia compared to NPH.

Topics: Aged; Alanine Transaminase; Biguanides; Blood Glucose; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Lispro; Insulin, Isophane; Male; Middle Aged; Polyethylene Glycols; Sulfonylurea Compounds; Thiazolidinediones; Triglycerides

To examine whether insulin glargine can lead to better control of glycated haemoglobin (HbA1c) than that achieved by neutral protamine Hagedorn (NPH) insulin, using a protocol designed to limit nocturnal hypoglycaemia.. The present study, the Least One Oral Antidiabetic Drug Treatment (LANCELOT) Study, was a 36-week, randomized, open-label, parallel-arm study conducted in Europe, Asia, the Middle East and South America. Participants were randomized (1:1) to begin glargine or NPH, on background of metformin with glimepiride. Weekly insulin titration aimed to achieve median prebreakfast and nocturnal plasma glucose levels ≤5.5 mmol/l, while limiting values ≤4.4 mmol/l.. The efficacy population (n = 701) had a mean age of 57 years, a mean body mass index of 29.8 kg/m², a mean duration of diabetes of 9.2 years and a mean HbA1c level of 8.2% (66 mmol/mol). At treatment end, HbA1c values and the proportion of participants with HbA1c <7.0 % (<53 mmol/mol) were not significantly different for glargine [7.1 % (54 mmol/mol) and 50.3%] versus NPH [7.2 % (55 mmol/mol) and 44.3%]. The rate of symptomatic nocturnal hypoglycaemia, confirmed by plasma glucose ≤3.9 or ≤3.1 mmol/l, was 29 and 48% less with glargine than with NPH insulin. Other outcomes were similar between the groups.. Insulin glargine was not superior to NPH insulin in improving glycaemic control. The insulin dosing algorithm was not sufficient to equalize nocturnal hypoglycaemia between the two insulins. This study confirms, in a globally heterogeneous population, the reduction achieved in nocturnal hypoglycaemia while attaining good glycaemic control with insulin glargine compared with NPH, even when titrating basal insulin to prevent nocturnal hypoglycaemia rather than treating according to normal fasting glucose levels.

Topics: Aged; Asia; Blood Glucose Self-Monitoring; Circadian Rhythm; Diabetes Mellitus, Type 2; Drug Dosage Calculations; Drug Resistance; Drug Therapy, Combination; Europe; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Metformin; Middle Aged; Middle East; South Africa; Sulfonylurea Compounds

The aim of this analysis was to assess the cost-effectiveness of switching from biphasic human insulin 30 (BHI), insulin glargine (IGlar), or neutral protamine Hagedorn (NPH) insulin (all ± oral glucose-lowering drugs [OGLDs]) to biphasic insulin aspart 30 (BIAsp 30) in people with type 2 diabetes in India, Indonesia, and Saudi Arabia.. The IMS CORE Diabetes Model was used to determine the clinical outcome, costs, and cost-effectiveness of switching from treatment with BHI, IGlar, or NPH to BIAsp 30 over a 30-year time horizon. A 1-year analysis was also performed based on quality-of-life data and treatment costs. Incremental cost-effectiveness ratios (ICERs) were expressed as a fraction of gross domestic product (GDP) per capita, and cost-effectiveness was defined as ICER <3-times GDP per capita.. Switching treatment from BHI, IGlar, or NPH to BIAsp 30 was associated with an increase in life expectancy of >0.7 years, reduction in all diabetes-related complications, and was considered as cost-effective or highly cost-effective in India, Indonesia, and Saudi Arabia (BHI to BIAsp 30, 0.26 in India, 1.25 in Indonesia, 0.01 in Saudi Arabia; IGlar to BIAsp 30, -0.68 in India, -0.21 in Saudi Arabia; NPH to BIAsp 30, 0.15 in India, -0.07 in Saudi Arabia; GDP per head per annum/quality-adjusted life-year). Cost-effectiveness was maintained in the 1-year analyses.. Switching from treatment with BHI, IGlar, or NPH to BIAsp 30 (all ± OGLDs) was found to be cost-effective in India, Indonesia, and Saudi Arabia, both in the long and short term.

Topics: Aged; Biphasic Insulins; Cost-Benefit Analysis; Diabetes Complications; Diabetes Mellitus, Type 2; Drug Combinations; Female; Humans; Hypoglycemic Agents; Incidence; India; Indonesia; Insulin Aspart; Insulin Glargine; Insulin, Isophane; Insulins; Life Expectancy; Male; Middle Aged; Quality of Life; Saudi Arabia

This study aimed to demonstrate the non-inferiority of 50-week treatment with stepwise insulin intensification of basal-bolus insulin analogues [insulin detemir (IDet) and aspart (IAsp)] versus biphasic insulin aspart 30 (BIAsp30) in insulin-naive type 2 diabetes mellitus (T2DM) patients not controlled by oral glucose-lowering drugs (OGLDs).. In this open-label multicentre, multinational, randomized, parallel-arm treat-to-target trial, 403 insulin-naive patients with T2DM in four African countries were randomized to either an IDet+IAsp (n = 200) or BIAsp1-2-3 (n = 203) treatment group. Stepwise insulin intensification was performed at the end of 14, 26 and 38 weeks, depending on HbA1c values. The primary endpoint was change in HbA1c after 50 weeks of treatment. Safety variables were hypoglycaemia incidence, occurrence of adverse events and weight gain.. Non-inferiority of the IDet+IAsp versus BIAsp1-2-3 treatment regimen was demonstrated by their similar HbA1c levels at the end of trial (IDet+IAsp: baseline 8.6%, 50 weeks 7.4%; BIAsp1-2-3: baseline 8.7%, 50 weeks 7.3%; full analysis set difference: 0.1% [95% CI: -0.1, 0.3]; per protocol: 0.2% [95% CI: -0.1, 0.4]). At week 50, 40.3 and 44.9% of patients achieved HbA1c <7.0% with IDet+IAsp and BIAsp1-2-3, respectively. The rate of overall hypoglycaemia during the trial was also similar in both groups (IDet+IAsp: 9.4 events/patient-year; BIAsp1-2-3: 9.8 events/patient-year).. Insulin initiation and intensification using IDet+IAsp was not inferior to BIAsp1-2-3 in insulin-naive patients with T2DM not controlled by OGLDs. Both regimens led to similar reductions in HbA1c values after 50 weeks of treatment.

Topics: Adult; Africa; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Male; Middle Aged

Investigate efficacy and tolerability of intensifying diabetes treatment with once- or twice-daily biphasic insulin aspart 30 (BIAsp 30) added to sitagliptin, and twice-daily BIAsp 30 without sitagliptin in patients with type 2 diabetes (T2D) inadequately controlled on sitagliptin.. Open-label, three-arm, 24-week trial; 582 insulin-naïve patients were randomized to twice-daily BIAsp 30+sitagliptin (BIAsp BID+Sit), once-daily BIAsp 30+sitagliptin (BIAsp QD+Sit) or twice-daily BIAsp 30 without sitagliptin (BIAsp BID), all with metformin.. After 24 weeks, HbA1c reduction (%) was superior with BIAsp BID+Sit vs. BIAsp QD+Sit (BIAsp BID+Sit minus BIAsp QD+Sit difference: -0.36 [95% CI -0.54; -0.17], P<0.001) and BIAsp BID (BIAsp BID minus BIAsp BID+Sit difference: 0.24 [0.06; 0.43], P=0.01). Observed final HbA1c values were 6.9%, 7.2% and 7.1% (baseline 8.4%), and 59.8%, 46.5% and 49.7% of patients achieved HbA1c <7.0%, respectively. Confirmed hypoglycaemia was lower with BIAsp QD+Sit vs. BIAsp BID (P=0.015); rate: 1.17 (BIAsp QD+Sit), 1.50 (BIAsp BID+Sit) and 2.24 (BIAsp BID) episodes/patient-year. Difference in bodyweight change favoured BIAsp QD+Sit vs. both BID groups (P<0.001).. Adding BIAsp 30 to patients with T2D poorly controlled with sitagliptin and metformin is efficacious and well tolerated; however, while BIAsp BID+Sit showed superior glycaemic control, BIAsp QD+Sit had a lower rate of hypoglycaemia and showed no weight gain.

Topics: Aged; Asia; Australia; Biomarkers; Biphasic Insulins; Blood Glucose; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Costs; Drug Therapy, Combination; Europe; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Male; Metformin; Middle Aged; Sitagliptin Phosphate; South America; Time Factors; Treatment Outcome

Insulin degludec/insulin aspart (IDegAsp) is a soluble co-formulation of IDeg and IAsp. This pan-Asian, 26-week trial investigated efficacy and safety of IDegAsp vs biphasic insulin aspart 30 (BIAsp 30) in Asian adults with type 2 diabetes (T2DM), inadequately controlled on once- or twice-daily (BID) basal, premixed or self-mixed insulin.. Participants (mean age 59.8 years, HbA1c 8.4%, FPG 7.9 mmol/L, BMI 25.4 kg/m(2)) were randomised 2:1 to BID IDegAsp (n=282) or BIAsp 30 (n=142) and continued existing metformin treatment. Insulins were administered with breakfast and main evening meal, titrated to a pre-breakfast and pre-main evening meal self-measured plasma glucose target of 4-5 mmol/L.. IDegAsp achieved the primary endpoint of non-inferiority to BIAsp 30 for mean change in HbA₁c (estimated treatment difference [ETD] IDegAsp-BIAsp 30: 0.05% points [95% CI -0.10; 0.20]). IDegAsp was superior in lowering fasting plasma glucose (FPG) (ETD -1.06 mmol/L, 95% CI -1.43; -0.70, p<0.001), and resulted in a lower final mean daily insulin dose (0.79 U/kg vs 0.99 U/kg, estimated rate ratio [RR] 0.79, 95% CI 0.73; 0.85, p<0.0001). Rates of overall confirmed and severe hypoglycaemia were similar between treatments, while rate of nocturnal confirmed hypoglycaemia was numerically (p=ns) lower with IDegAsp. During the maintenance period there was a trend (p=ns) towards lower hypoglycaemia rates for IDegAsp.. In Asian adults with T2DM, IDegAsp BID effectively improves long-term glycaemic control, and compared to BIAsp 30, provides superior reductions in FPG with a lower dose, and numerically less nocturnal hypoglycaemia.

Topics: Adult; Aged; Asian People; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Drug Combinations; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Metformin; Middle Aged; Treatment Failure

Clinical guidelines recommend point-of-care glucose testing and the use of supplemental doses of rapid-acting insulin before meals and at bedtime for correction of hyperglycemia. The efficacy and safety of this recommendation, however, have not been tested in the hospital setting.. In this open-label, randomized controlled trial, 206 general medicine and surgery patients with type 2 diabetes treated with a basal-bolus regimen were randomized to receive either supplemental insulin (n = 106) at bedtime for blood glucose (BG) >7.8 mmol/L or no supplemental insulin (n = 100) except for BG >19.4 mmol/L. Point-of-care testing was performed before meals, at bedtime, and at 3:00 a.m. The primary outcome was the difference in fasting BG. In addition to the intention-to-treat analysis, an as-treated analysis was performed where the primary outcome was analyzed for only the bedtime BG levels between 7.8 and 19.4 mmol/L.. There were no differences in mean fasting BG for the intention-to-treat (8.8 ± 2.4 vs. 8.6 ± 2.2 mmol/L, P = 0.76) and as-treated (8.9 ± 2.4 vs. 8.8 ± 2.4 mmol/L, P = 0.92) analyses. Only 66% of patients in the supplement and 8% in the no supplement groups received bedtime supplemental insulin. Hypoglycemia (BG <3.9 mmol/L) did not differ between groups for either the intention-to-treat (30% vs. 26%, P = 0.50) or the as-treated (4% vs. 8%, P = 0.37) analysis.. The use of insulin supplements for correction of bedtime hyperglycemia was not associated with an improvement in glycemic control. We conclude that routine use of bedtime insulin supplementation is not indicated for management of inpatients with type 2 diabetes.

Topics: Aged; Blood Glucose; Circadian Rhythm; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Hospitalization; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Lispro; Insulin, Isophane; Insulin, Long-Acting; Insulin, Short-Acting; Male; Meals; Middle Aged; Sleep

There is limited evidence to guide the selection of second-line anti-hyperglycemic agents in patients with type 2 diabetes mellitus (T2DM) who are inadequately controlled with sulfonylurea monotherapy and are intolerant to metformin. We compared the efficacy and safety of vildagliptin 50 mg qd and Neutral Protamine Hagedorn (NPH) insulin qd in such patients.. This was a 24 week, multicenter, randomized, open-label study. The co-primary endpoints were (i) proportion of patients achieving HbA1c <7.0% without any confirmed hypoglycemic events (HEs) or weight gain ≥3% (composite endpoint); (ii) rate of confirmed HEs. Treatment satisfaction was assessed using the TSQM-9 questionnaire at study end.. A total of 162 patients were randomly assigned to vildagliptin (n = 83) and NPH insulin (n = 79). Similar proportion of patients achieved the composite endpoint in vildagliptin versus NPH insulin group (35.4% versus 34.2%; OR 0.985; 95% CI 0.507, 1.915; p = 0.96). After 24 weeks, 48.8% of patients in the vildagliptin group and 60.8% in the NPH insulin group achieved HbA1c <7.0%; 13.4% in the vildagliptin group and 29.1% in the insulin group had at least one confirmed HE; while 11.0% in the vildagliptin group and 22.8% in the insulin group experienced weight gain. The rate of confirmed HEs was significantly lower in patients receiving vildagliptin versus NPH insulin (1.3 versus 5.1 events per year). The TSQM-9 score for 'convenience' at week 24 increased significantly more with vildagliptin than with NPH insulin.. Addition of vildagliptin and NPH insulin resulted in a similar number of patients reaching HbA1c target without HEs or weight gain in T2DM patients inadequately controlled with sulfonylurea. The addition of vildagliptin to sulfonylurea could be considered as a treatment option prior to intensification with insulin, with the advantages of a lower HE rate and greater patient convenience. Study results are limited by a higher drop-out rate in the vildagliptin arm.

Topics: Adamantane; Adult; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin, Isophane; Male; Middle Aged; Nitriles; Pyrrolidines; Sulfonylurea Compounds; Vildagliptin; Weight Gain

We sought to determine if insulin detemir (IDet) is noninferior to insulin neutral protamine Hagedorn (NPH) for the treatment of gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM) in pregnancy.. We conducted a randomized, controlled noninferiority trial of women with GDM and T2DM who entered our Diabetes in Pregnancy Program from March 2013 through October 2014. Exclusion criteria were type 1 diabetes, age <18 years, and insulin allergy. Women who failed to achieve good glycemic control (GC) (mean blood glucose [BG] <100 mg/dL) on diet and/or hypoglycemic agents were randomized to receive either IDet or NPH, with short-acting insulin aspart added as needed. Patients were instructed to test BG 4 times a day (fasting and 2-hour postprandial). Targets of GC were fasting BG <90 mg/dL and postprandial BG <120 mg/dL, and insulin was adjusted as needed to achieve the targets. The primary outcome was overall mean BG during insulin treatment; secondary outcomes included overall mean postprandial and fasting BG, median number of weeks to achieve GC, percent of patients with overall GC, maternal weight gain, perinatal/neonatal outcomes, and number of hypoglycemic events. Power analysis (90% power) determined that 88 patients would need to be randomized, assuming a maximal acceptable difference in overall mean BG of 7 mg/dL (SD ± 10 mg/dL). A per protocol analysis was performed.. In all, 105 women were randomized. Eighteen women were excluded leaving 87 participants for analysis (45 NPH, 42 IDet). Maternal characteristics were similar in both groups. The difference in the mean BG of the groups was 2.1 mg/dL with a 1-sided upper 95% confidence limit of 5.5 mg/dL (less than the maximal acceptable difference of 7 mg/dL; P = .2937). There was no significant difference in the primary outcome when an intent-to-treat analysis was performed or when the T2DM patients were excluded. The time to achieve GC was similar in both groups. There were no differences in perinatal outcomes and maternal weight gain among the groups. There were more hypoglycemic events per patient in the NPH group.. IDet is noninferior to insulin NPH for the treatment of GDM and T2DM in pregnancy.

Topics: Adolescent; Adult; Diabetes Mellitus, Type 2; Diabetes, Gestational; Drug Administration Schedule; Female; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Intention to Treat Analysis; Pregnancy; Pregnancy in Diabetics; Treatment Outcome; Young Adult

To test the hypothesis that a 'basal plus' regimen--adding once-daily main-meal fast-acting insulin to basal insulin once daily--would be non-inferior to biphasic insulin twice daily as assessed by glycated haemoglobin (HbA1c) concentration (predefined as ≤0.4%), but would provide superior treatment satisfaction.. This open-label trial enrolled adults to an 8- or 12-week run-in period, during which oral therapies except metformin were stopped and insulin glargine dose was titrated. Those with fasting glucose <7 mmol/l but HbA1c >7% (53 mmol/mol) were randomized to insulin glargine/glulisine once daily (n = 170) or insulin aspart/aspart protamine 30/70 twice daily (n = 165) for 24 weeks, with dose titration to glucose targets using standardized algorithms.. For HbA1c, the basal plus regimen was non-inferior to biphasic insulin (least squares mean difference, 0.21%, upper 97.5% confidence limit 0.38%) meeting the predefined non-inferiority margin of 0.4%. Treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire change version and Insulin Treatment Satisfaction Questionnaire total scores) significantly favoured basal plus. No difference was observed between the basal plus and the biphasic insulin groups in responders (HbA1c <7%, 20.6 vs 27.9%; p = 0.12), weight gain (2.06 vs 2.50 kg; p = 0.2), diabetes-specific quality of life (Audit of Diabetes-Dependent Quality of Life average weighted impact (AWI) score) and generic health status (five-dimension European Quality of Life questionnaire). Overall hypoglycaemia rates were similar between groups (15.3 vs 18.2 events/patient-year; p = 0.22); nocturnal hypoglycaemia was higher with the basal plus regimen (5.7 vs 3.6 events/patient-year; p = 0.02).. In long-standing type 2 diabetes with suboptimal glycaemia despite oral therapies and basal insulin, the basal plus regimen was non-inferior to biphasic insulin for biomedical outcomes, with a similar overall hypoglycaemia rate but more nocturnal events.

Topics: Aged; Australia; Biphasic Insulins; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Isophane; Intention to Treat Analysis; Male; Middle Aged; Patient Dropouts; Quality of Life; United Kingdom

To evaluate the effect of liraglutide and NPH on blood glucose fluctuations in patients with newly diagnosed type 2 diabetes mellitus (T2DM).. A total of 63 newly diagnosed T2DM patients were randomized into a liraglutide group and an NPH group. They were treated for 12 weeks. The values of CGM, HbA1C, and BMI were measured and compared before and after treatment.. FPG, HbAlc, and MBG were decreased in both groups after 12 weeks of treatment. In the liraglutide group, the MAGE, SDBG, LAGE, BMI, and waist circumference were significantly 1ower than in the NPH group (p<0.05). Patients in the liraglutide group had a greater incidence of gastrointestinal adverse effects than in the NPH group (p<0.05). The incidence of hypoglycemia episode in the liraglutide group was significantly lower than in the NPH group (p<0.05).. Liraglutide achieved improvements in overall glycemic control similar to NPH in patients with newly diagnosed T2DM. Liraglutide was associated with less glucose fluctuation than NPH treatment as assessed by CGM. In addition, patients in the liraglutide group had a greater incidence of gastrointestinal adverse effects, a lower incidence of hypoglycemia, and some weight reduction.

Topics: Adult; Aged; Biomarkers; Blood Glucose; Body Mass Index; China; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Gastrointestinal Diseases; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin, Isophane; Liraglutide; Male; Metformin; Middle Aged; Monitoring, Ambulatory; Predictive Value of Tests; Prospective Studies; Time Factors; Treatment Outcome; Waist Circumference

Premixed insulin is a commonly prescribed formulation for the outpatient management of patients with type 2 diabetes. The safety and efficacy of premixed insulin formulations in the hospital setting is not known.. In a prospective, open-label trial, we randomized general medicine and surgery patients to receive a basal-bolus regimen with glargine once daily and glulisine before meals (n = 33) or premixed human insulin (30% regular insulin and 70% NPH insulin) twice daily (n = 39). Major outcomes included differences in daily blood glucose (BG) levels and frequency of hypoglycemic events (<70 mg/dL) between treatment groups.. At the first prespecified interim analysis, the study was stopped early because of an increased frequency of hypoglycemia >50% in patients treated with premixed human insulin. A total of 64% of patients treated with premixed insulin experienced one or more episodes of hypoglycemia compared with 24% in the basal-bolus group (P < 0.001). There were no differences in mean daily BG level after the first day of insulin treatment (175 ± 32 vs. 179 ± 43 mg/dL, P = 0.64) between groups. A BG target between 80 and 180 mg/dL before meals was achieved in 55.9% of BG readings in the basal-bolus group and 54.3% of BG readings in the premixed insulin group (P = 0.23). There was no difference in the length of hospital stay or mortality between treatment groups.. Inpatient treatment with premixed human insulin resulted in similar glycemic control but in significantly higher frequency of hypoglycemia compared with treatment with basal-bolus insulin regimen in hospitalized patients with diabetes.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Combinations; Female; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Regular, Human; Male; Middle Aged; Prospective Studies

To investigate the clinical efficacy and safety of insulin glargine compared with NPH insulin as basal insulin for the management of corticosteroid-induced hyperglycemia in hospitalized people with type 2 diabetes (T2DM) and respiratory disease.. Randomized, two-arm parallel group, clinical trial undertaken from February 2011 to November 2012 on the pneumology ward of the Hospital Regional Universitario de Málaga (Spain), involving 53 participants with T2DM treated with medium/high doses of intermediate-acting corticosteroids. Participants were randomly assigned to receive one single dose of insulin glargine or NPH insulin in three equally divided doses before each meal as basal insulin within a basal-bolus insulin protocol. The intervention lasted six days or until discharge if earlier.. No significant differences were seen between groups during the study in mean blood glucose (11.43±3.44 mmol/l in glargine vs. 11.88±2.94 mmol/l in NPH, p=0.624), and measures of glucose variability (standard deviation 3.27±1.16 mmol/l vs. 3.61±0.99 mmol/l, p=0.273; coefficient of variation 1.55±0.33 mmol/l vs. 1.72±0.39 mmol/l, p=0.200). Results from CGM were concordant with those obtained with capillary blood glucose reading. The length of hospital stay was also similar between groups (8.2±2.8 days vs. 9.8±3.4 days, p=0.166) There was a non significant trend for lower episodes of mild (4 vs. 8, p=0.351) and severe hypoglycemia (0 vs. 3, p=0.13) in the glargine group.. The results of this study showed that insulin glargine and NPH insulin are equally effective in a basal-bolus insulin protocol to treat glucocorticoid-induced hyperglycemia in people with T2DM on a pneumology ward.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Male; Middle Aged; Respiratory Tract Diseases; Safety; Young Adult

Our aim was to compare the effects of an intermediate acting human insulin (NPH) and a long-acting insulin analog, insulin glargine, in insulin naïve type 2 diabetes patients, stratified by the type of hyperglycemia (fasting or postprandial type). Based on different action profiles, we hypothesized that patients having different hyperglycemia types would react differently when treated with these insulins. This is a post hoc analysis of the Lanmet study data. The Lanmet study was a randomized, 36-week controlled insulin initiation study in type 2 diabetes patients. 109 subjects with baseline HbA1c >8.0% (64 mmol/mol) completed the study. The patients were divided into two groups according to fasting glucose (mmol/l)/HbA1c (%) ratio. Patients with a ratio ≥1.3 were defined as having fasting type and those with a ratio <1.3 as having postprandial type hyperglycemia. The main outcome measures were change in HbA1c and body weight, and final insulin dose. Independently of insulin type, compared to patients with postprandial type hyperglycemia, those with fasting type hyperglycemia had 2.1 kg/m(2) greater initial BMI (p = 0.044), gained 2.0 kg more weight (p = 0.020, adjusted for baseline BMI p = 0.035), and had 36% greater final insulin dose/kg (p = 0.001). With respect to hyperglycemia type, there was no difference between NPH and glargine in their effects on HbA1c. When starting bedtime insulin in type 2 diabetes patients, those with fasting type hyperglycemia are prone to greater weight gain. Hyperglycemia type does not help in identifying patients who would benefit specially from either NPH insulin or insulin glargine.

Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Fasting; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Insulin Glargine; Insulin, Isophane; Male; Middle Aged; Postprandial Period; Statistics, Nonparametric

Few studies have evaluated long-term durability of glycemic control in older patients. The aim of this study was to compare durability of glycemic control of twice-daily insulin lispro mix 75/25 (LM75/25; 75 % insulin lispro protamine suspension, 25 % insulin lispro) and once-daily insulin glargine (GL) added to oral antihyperglycemic medications in older patients (≥65 years of age).. Patients were participants in the maintenance phase of the DURABLE trial. During the initiation phase, patients with type 2 diabetes were randomized to LM75/25 or GL. After 6 months, patients with hemoglobin A1c (HbA1c) ≤7.0 % advanced to the 24-month maintenance phase. The primary objective was between-group comparison of duration of maintaining the HbA1c goal in older patients (≥65 years of age). A similar analysis was conducted for older patients achieving HbA1c ≤6.5 % in the initiation phase.. Median time of maintaining HbA1c goal was longer in LM75/25 versus GL (19.6 versus 15.4 months, p = 0.007) and more LM75/25 patients maintained goal versus GL (49.2 versus 30.4 %; p = 0.003). HbA1c reduction from baseline was greater in LM75/25 versus GL (-1.56 ± 0.10 versus -1.24 ± 0.11 %; p = 0.003). Post-meal glucose was significantly lower in LM75/25 versus GL (158.86 ± 3.42 versus 171.67 ± 4.51 mg/dL; p = 0.017). No differences were observed in overall and severe hypoglycemia. LM75/25 patients had higher daily insulin doses (0.41 ± 0.02 versus 0.32 ± 0.02 units/kg/day; p < 0.001) and more weight gain (5.47 ± 0.49 versus 3.10 ± 0.53 kg; p = 0.001). Similar results were generally obtained in older patients with HbA1c ≤6.5 %.. In our evaluation of older patients from a larger trial, LM75/25 appeared to provide longer durability of glycemic control, as well as a greater number of patients maintaining HbA1c goal versus GL.

Topics: Aged; Aging; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin Lispro; Insulin, Isophane; Insulin, Long-Acting; Maintenance Chemotherapy; Male

Glucose variability combined with glycosylated hemoglobin (HbA1c) assessments more reliably represents the level of glycemic control. The study was aimed to compare blood glucose variability with insulin glargine vs. neutral protamine Hagedorn (NPH) in patients with type 2 diabetes mellitus using a continuous glucose-monitoring system (CGMS), in patients treated with basal insulin using stable dose of oral antidiabetic agents and HbA1c in the range of 4.5-8.0 % International Federation of Clinical Chemistry (IFCC) units. [6.2-9.4 % Diabetes Control and Complications Trial (DCCT) units].. This was a multicenter, prospective, open-label, single-arm study in patients (N = 116) treated for ≥ 2 months with NPH and metformin combined with sulfonylurea or glinide. Glucose variability was measured after a 4-week NPH treatment phase and after a subsequent 12-week glargine treatment phase using CGMS. Based on 72-hour CGMS, glucose variability was assessed by area under the curve [AUC (mmol/L · h)]. Differences (glargine-NPH) in AUC within 24 h in the glucose ranges of ≤ 3.3, ≤ 3.9, 7.5-3.9 (margins excluding), ≥ 7.5, ≥ 10, and ≥ 15 mmol/L were evaluated. Circadian fluctuation of glucose was assessed by M-value (log-transformation of the deviation from an arbitrary standard).. AUCs of glucose in the lowest ranges (≤ 3.3 and ≤ 3.9 mmol/L) did not change significantly after treatment with glargine. Those in the higher ranges (≥ 7.5, ≥ 10, and ≥ 15 mmol/L) were significantly lower (p < 0.001 for all ranges), whereas AUC of glucose in the normal range (3.9-7.5 mmol/L) was significantly higher (p < 0.001) at the end of glargine treatment phase. Circadian fluctuation of glucose assessed by M-value showed a significant decrease after glargine treatment (p < 0.003). No significant differences in hypoglycemia confirmed by glucose value ≤ 3.3 mmol/L were found between treatment phases. This trial is registered at ClinicalTrials.gov, NCT00659477.. As monitored by CGMS, switching from NPH to glargine with active titration shifted glucose from abnormally high to normal levels with reduced fluctuation and without increased risk of hypoglycemia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Czech Republic; Diabetes Mellitus, Type 2; Drug Monitoring; Drug Substitution; Female; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Reproducibility of Results; Sensitivity and Specificity; Treatment Outcome; Young Adult

Insulin degludec/insulin aspart (IDegAsp) is the first combination of a basal insulin with an ultralong duration of action, and a rapid-acting insulin in a single injection. This trial compared IDegAsp with biphasic insulin aspart 30 (BIAsp 30) in adults with type 2 diabetes inadequately controlled with once- or twice-daily (OD or BID) pre- or self-mixed insulin with or without oral antidiabetic drugs.. In this 26-week, randomized, open-label, multinational, treat-to-target trial, participants (mean age 58.7 years, duration of diabetes 13 years, BMI 29.3 kg/m(2), and HbA1c 8.4% [68 mmol/mol]) were exposed (1:1) to BID injections of IDegAsp (n = 224) or BIAsp 30 (n = 222), administered with breakfast and the main evening meal and dose titrated to a self-measured premeal plasma glucose (PG) target of 4.0-5.0 mmol/L.. After 26 weeks, mean HbA1c was 7.1% (54 mmol/mol) for both groups, with IDegAsp achieving the prespecified noninferiority margin for mean change in HbA1c (estimated treatment difference [ETD] -0.03% points [95% CI -0.18 to 0.13]). Treatment with IDegAsp was superior in lowering fasting PG (ETD -1.14 mmol/L [95% CI -1.53 to -0.76], P < 0.001) and had a significantly lower final mean daily insulin dose (estimated rate ratio 0.89 [95% CI 0.83-0.96], P = 0.002). Fewer confirmed, nocturnal confirmed, and severe hypoglycemia episodes were reported for IDegAsp compared with BIAsp 30.. IDegAsp BID effectively improves HbA1c and fasting PG levels with fewer hypoglycemia episodes versus BIAsp 30 in patients with uncontrolled type 2 diabetes previously treated with once- or twice-daily pre- or self-mixed insulin.

Topics: Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections; Insulin Aspart; Insulin, Isophane; Insulin, Long-Acting; Male; Meals; Middle Aged; Treatment Outcome

The study aimed to confirm the efficacy, through non-inferiority, of patient-driven versus investigator-driven titration of biphasic insulin aspart 30 (BIAsp 30) in terms of glycemic control assessed by HbA1c change.. SimpleMix was a 20 week, open-label, randomized, two-armed, parallel-group, multicenter study in five countries (Argentina, China, India, Poland, and the UK). Patients with type 2 diabetes were randomized into either patient-driven or investigator-driven BIAsp 30 titration groups.. Non-inferiority of patient-driven vs. investigator-driven titration based on change in HbA1c from baseline to week 20 could not be demonstrated. Mean (SE) estimated change from baseline to week 20 was -0.72 (0.08)% in the patient-driven group and -0.97 (0.08)% in the investigator-driven group; estimated difference 0.25% (95% CI: 0.04; 0.46). Estimated mean change (SE) in fasting plasma glucose from baseline to week 20 was similar between groups: -0.94 (0.21) mmol/L for patient-driven and -1.07 (0.22) mmol/L for investigator-driven (difference non-significant). Both treatment arms were well tolerated, and hypoglycemic episode rates were similar between groups, with a rate ratio of 0.77 (95% CI: 0.54; 1.09; p = 0.143) for all hypoglycemic episodes and 0.78 (95% CI: 0.42; 1.43; p = 0.417) for nocturnal hypoglycemic episodes.. Non-inferiority of patient-driven versus investigator-driven titration with regard to change from baseline to end-of-treatment HbA1c could not be confirmed. It is possible that a clinic visit 12 weeks after intensification of treatment with BIAsp 30 in patients with type 2 diabetes inadequately treated with basal insulin may benefit patient-driven titration of BIAsp 30. A limitation of the study was the relatively small number of patients recruited in each country, which does not allow country-specific analyses to be performed. Overall, treatment with BIAsp 30 was well tolerated in both treatment groups.

Topics: Adult; Aged; Biphasic Insulins; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Outcome Assessment, Health Care; Self Administration

Based on the 24-week, prospective, non-interventional, observational study, A1chieve®, we investigated how health-related quality of life (HRQoL) changed, and the predictors of such changes, in Chinese people with type 2 diabetes mellitus (T2DM) after starting with, or switching to, biphasic insulin aspart 30 (BIAsp 30).. In total, 8,578 people with T2DM starting treatment with, or switching to, BIAsp 30 were recruited from 130 urban hospitals in China. HRQoL was assessed at baseline and 24 weeks using the EuroQol-5 dimensions (EQ-5D) questionnaire. Descriptive statistics, paired t-test, and chi-square test were conducted and the linear ordinary least squares regression model was used to determine predictors for changes in EQ-5D score.. Haemoglobin A1c (HbA1c) decreased from 9.5% to 7.0% after 24 weeks. The reported HRQoL measured by the EQ-5D visual analogue scale score increased by 6.2 (p < 0.001) from 75.8 to 82.0, and EQ-5D index score increased by 0.018 (p < 0.001) from 0.875 to 0.893 for the cohort over 24 weeks. The percentage of patients reporting no problems in the mobility, pain/discomfort, and anxiety/depression dimensions of EQ-5D increased significantly (p < 0.001) from 88.4% to 91.4%, 77.3% to 82.8%, and 74.2% to 77.1%, respectively. Patients with higher HbA1c levels at baseline, major hypoglycaemia or micro-complications exhibited significantly larger changes in EQ-5D scores than those with lower baseline HbA1c levels, without major hypoglycaemia or micro-complications after controlling for demographics and other baseline characteristics.. BIAsp 30 treatment was associated with improved glycaemic control and HRQoL in T2DM patients in China. Patients with worse health conditions were more likely to experience larger improvements in HRQoL than those with better health conditions.. ClinicalTrials.gov, NCT00869908 .

Topics: Adult; Aged; Biphasic Insulins; China; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Prospective Studies; Quality of Life; Surveys and Questionnaires; Treatment Outcome

We investigated 1) the ability of purified glargine (GLA), metabolites 1 (M1) and 2 (M2), IGF-I, and NPH insulin to activate the insulin receptor (IR)-A and IR-B and IGF-I receptor (IGF-IR) in vitro; 2) plasma concentrations of GLA, M1, and M2 during long-term insulin therapy in type 2 diabetic patients; and 3) IR-A and IR-B activation in vitro induced by serum from patients treated with GLA or NPH insulin. A total of 104 patients (age 56.3 ± 0.8 years, BMI 31.4 ± 0.5 kg/m(2), and A1C 9.1 ± 0.1% [mean ± SE]) were randomized to GLA or NPH insulin therapy for 36 weeks. Plasma concentrations of GLA, M1, and M2 were determined by liquid chromatography-tandem mass spectrometry assay. IR-A, IR-B, and IGF-IR autophosphorylation was induced by purified hormones or serum by kinase receptor activation assays. In vitro, M1 induced comparable IR-A, IR-B, and IGF-IR autophosphorylation (activation) as NPH insulin. After 36 weeks, M1 increased from undetectable (<0.2 ng/mL) to 1.5 ng/mL (0.9-2.1), while GLA and M2 remained undetectable. GLA dose correlated with M1 (r = 0.84; P < 0.001). Serum from patients treated with GLA or NPH insulin induced similar IR-A and IR-B activation. These data suggest that M1 rather than GLA mediates GLA effects and that compared with NPH insulin, GLA does not increase IGF-IR signaling during long-term insulin therapy in type 2 diabetes.

Topics: Chromatography, Liquid; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin-Like Growth Factor I; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Receptor, IGF Type 1; Receptor, Insulin; Signal Transduction; Tandem Mass Spectrometry

To assess the cost-effectiveness of insulin detemir compared with Neutral Protamine Hagedorn (NPH) insulin when initiating insulin treatment in people with type 2 diabetes mellitus (T2DM) in Denmark, Finland, Norway, and Sweden.. Efficacy and safety data were derived from a 20-week multi-centre randomized controlled head-to-head clinical trial comparing insulin detemir and NPH insulin in insulin naïve people with T2DM, and short-term (1-year) cost effectiveness analyses were performed. As no significant differences in HbA1c were observed between the two treatment arms, the model was based on significant differences in favour of insulin detemir in frequency of hypoglycaemia (Rate-Ratio = 0.52; CI = 0.44-0.61) and weight gain (Δ = 0.9 kg). Model outcomes were measured in Quality Adjusted Life Years (QALYs) using published utility estimates. Acquisition costs for insulin and direct healthcare costs associated with non-severe hypoglycaemic events were obtained from National Health Service public sources. One-way and probabilistic sensitivity analyses were performed.. Based on lower incidence of non-severe hypoglycaemic events and less weight gain, the QALY gain from initiating treatment with insulin detemir compared with NPH insulin was 0.01 per patient per year. Incremental cost-effectiveness ratios for the individual countries were: Denmark, Danish Kroner 170,852 (€22,933); Finland, €28,349; Norway, Norwegian Kroner 169,789 (€21,768); and Sweden, Swedish Krona 226,622 (€25,097) per QALY gained. Possible limitations of the study are that data on hypoglycaemia and relative weight benefits from a clinical trial were combined with hypoglycaemia incidence data from observational studies. These populations may have slightly different patient characteristics.. The lower risk of non-severe hypoglycaemia and less weight gain associated with using insulin detemir compared with NPH insulin when initiating insulin treatment in insulin naïve patients with type 2 diabetes provide economic benefits in the short-term. Based on cost/QALY threshold values, this represents good value for money in the Nordic countries. Using a short-term modelling approach may be conservative, as reduced frequency of hypoglycaemia and less weight gain may also have positive long-term health-related implications.

Topics: Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Finland; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Models, Economic; Quality-Adjusted Life Years; Reproducibility of Results; Scandinavian and Nordic Countries; Weight Gain

In type 2 diabetic patients, insulin detemir (B29Lys(ε-tetradecanoyl),desB30 human insulin) induces less weight gain than NPH insulin. Due to the proposed reduction of tubular action by insulin detemir, type 2 diabetic patients should have increased urinary sodium excretion, thereby reducing extracellular volume and body weight when changed from NPH insulin to insulin detemir.. In a randomised, open-labelled, two-way crossover study of 24 patients with type 2 diabetes, patients were first treated with NPH insulin or insulin detemir for 8 weeks. Thereafter, they were changed to the other insulin for 8 weeks. In a third 1 week period, they were changed back to the first insulin.. At the end of 8 weeks, body weight was reduced by 0.8 ± 0.2 kg (mean ± SEM) on insulin detemir compared with NPH insulin (p < 0.01). After insulin detemir treatment, we also observed a significant reduction of lean body mass (0.8 ± 0.2 kg, p < 0.05) and a non-significant reduction of extracellular volume (0.8 ± 0.5 l/1.73 m², p = 0.14). The weight loss occurred after as early as 1 week (0.8 ± 0.2 kg, p < 0.001), with a simultaneous and transient increase of urinary sodium excretion (p = 0.07).. Insulin detemir induces significant and sustained weight loss, which is first observed at 1 week after changing from NPH insulin. The initial weight loss seems to be related to changes in fluid volume and may reflect changed insulin action in the kidneys.

Topics: Aged; Body Composition; Cross-Over Studies; Diabetes Mellitus, Type 2; Extracellular Fluid; Fluid Shifts; Glomerular Filtration Rate; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Insulin, Regular, Human; Isophane Insulin, Human; Middle Aged; Outpatient Clinics, Hospital; Patient Dropouts; Sodium; Time Factors; Water-Electrolyte Balance; Weight Loss

Assess safety and glycaemic control in patients initiating insulin with, or switching from basal insulin to, biphasic insulin aspart 30/70 (BIAsp 30) in primary care in Finland.. A non-randomised, non-interventional, open-label, 26-week study of type 2 diabetes (T2D) patients prescribed BIAsp 30 by their physician, who determined starting dose, titration and injection frequency.. 496 patients provided safety data (insulin-naïve n=197; prior insulin n=299 [84.9% received NPH insulin]). Three patients (0.6%) reported four SADRs (three hypoglycaemia, one hypoglycaemia with unconsciousness). HbA1c was significantly (p<0.0001) reduced after 26 weeks' BIAsp 30 therapy (final dose): insulin-naïve -1.4% (44.4 IU); prior insulin -1.1% (77.4 IU). HbA1c<7.0% was achieved by 10% of insulin-naïve patients at baseline and 51% at 26-week follow-up. In the prior insulin group, 7% and 30% of patients had HbA1c<7.0% at baseline and 26 weeks, respectively. Minor hypoglycaemia increased significantly from baseline to study end: insulin-naïve 0.66-6.45 events/patient/year (p<0.0001); prior insulin 5.11-8.58 events/patient/year (p<0.05). Weight increased by 1.0 kg (insulin-naïve) and 1.3 kg (previous insulin).. BIAsp 30, initiated and titrated in T2D patients in primary care in Finland, showed a good safety profile and significantly improved glycaemic control.

Topics: Adult; Aged; Aged, 80 and over; Biphasic Insulins; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Finland; Follow-Up Studies; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Primary Health Care; Treatment Outcome

Acute hyperglycaemia induces coagulation activation in diabetes patients. We hypothesized that rapid-acting insulin has a beneficial postprandial effect on coagulation and fibrinolysis compared with intermediate-acting insulin because of its ability to lower postprandial hyperglycaemia.. This was tested in a parallel controlled study in well-controlled patients with type 2 diabetes assigned to bedtime neutral protamine Hagedorn (NPH) insulin (n = 41) or mealtime insulin aspart (n = 37). They were served standard diabetic meals for breakfast (8:00 hours) and lunch (12:00 hours). Blood samples were collected at 7:40 hours (fasting), 9:30, 11:30, 13:30 and 15:30 hours and analysed for glucose, activated factor VII (FVIIa), D-dimer, prothrombin fragment 1+2 (F1+2), tissue plasminogen activator antigen (t-PA) and plasminogen activator inhibitor activity (PAI).. The postprandial glucose response differed significantly between insulin regimens with a postprandial increase on NPH insulin and a decrease on insulin aspart. There was a significant postprandial decrease in F1+2, PAI and t-PA, and no changes in FVIIa and D-dimer, on both insulin regimens, but with no differences between insulin treatment groups.. The rapid-acting insulin analogue aspart and the intermediate-acting insulin NPH had similar postprandial effects on markers of coagulation activation and fibrinolysis despite different effects on postprandial glucose response.

Topics: Biomarkers; Blood Coagulation; Diabetes Mellitus, Type 2; Female; Fibrinolysis; Humans; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Postprandial Period

The aim of this study was to compare IGF-I bioactivity 36 weeks after the addition of insulin glargine (A21Gly,B31Arg,B32Arg human insulin) or NPH insulin to metformin therapy in type 2 diabetic patients who had poor glucose control under metformin monotherapy.. In the Lantus plus Metformin (LANMET) study, 110 poorly controlled insulin-naive type 2 diabetic patients were randomised to receive metformin with either insulin glargine (G+MET) or NPH insulin (NPH+MET). In the present study, IGF-I bioactivity was measured, retrospectively, in 104 out of the 110 initially included LANMET participants before and after 36 weeks of insulin therapy. IGF-I bioactivity was measured using an IGF-I kinase receptor activation assay.. After 36 weeks of insulin therapy, insulin doses were comparable between the G+MET (68 ± 5.7 U/day) and NPH+MET (71 ± 6.2 U/day) groups (p = 0.68). Before insulin therapy, circulating IGF-I bioactivity was similar between the G+MET (134 ± 9 pmol/l) and NPH+MET (135 ± 10 pmol/l) groups (p = 0.83). After 36 weeks, IGF-I bioactivity had decreased significantly (p = 0.001) and did not differ between the G+MET (116 ± 9 pmol/l) and NPH+MET (117 ± 10 pmol/l) groups (p = 0.91). At baseline and after insulin therapy, total IGF-I concentrations were comparable in both groups (baseline: G+MET 13.3 ± 1.0 vs NPH+MET 13.3 ± 1.0 nmol/l, p = 0.97; and 36 weeks: 13.4 ± 1.0 vs 13.1 ± 0.9 nmol/l, p = 0.71). Total IGF-I concentration did not change during insulin therapy (13.3 ± 0.7 vs 13.3 ± 0.7 nmol/l, baseline vs 36 weeks, p = 0.86).. Addition of insulin glargine or NPH insulin to metformin monotherapy in poorly controlled type 2 diabetic patients decreases serum IGF-I bioactivity in a similar manner.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin-Like Growth Factor I; Insulin, Isophane; Insulin, Long-Acting; Male; Metformin; Middle Aged

To compare the safety and efficacy of adding insulin glargine or neutral protamine Hagedorn (NPH) insulin to existing oral antidiabetic drug (OAD) regimens in adults with type 2 diabetes mellitus.. Pooled analysis of data from five randomized controlled trials with similar designs.. Three hundred forty-two centers in more than 30 countries worldwide.. Randomly selected individuals aged ≤ 80 with a body mass index ≤ 40 kg/m(2) and a glycosylated hemoglobin (HbA1c) level of 7.5% to 12.0%.. Fixed- and random-effects models were used to compare outcomes after 24 or 28 weeks of treatment (insulin glargine, n = 1,441; NPH insulin, n = 1,254) according to age (≥65, n = 604 vs < 65, n = 2,091) and age based on treatment (e.g., ≥65 receiving insulin glargine vs NPH insulin). Outcomes included change in HbA1c, fasting blood glucose (FBG), insulin dose, and hypoglycemia incidence and event rates.. At end point, participants aged 65 and older receiving insulin glargine had greater reductions in HbA1c and FBG than those receiving similar doses of NPH insulin. In contrast, for participants younger than 65, there were no statistically significant differences in reductions in HbA1c or FBG between insulin glargine and NPH insulin. Daytime hypoglycemia rates were similar in all groups, although the rates of nocturnal symptomatic and severe hypoglycemia were lower with insulin glargine than NPH insulin.. Addition of insulin glargine to oral antidiabetic drugs in older adults with poor glycemic control may have modestly better glycemic benefits than adding NPH insulin, with low risk of hypoglycemia.

Topics: Adult; Age Distribution; Age Factors; Aged; Aged, 80 and over; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Global Health; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Prospective Studies; Treatment Outcome

To determine if self-titration using biphasic insulin aspart 70/30 (BIAsp 30) had a different impact on efficacy and safety across different racial/ethnic subgroups.. This was an exploratory, post hoc analysis by race (White vs. Black/African-American) and ethnicity (Hispanic/Latino vs. non-Hispanic/Latino) of data from the INITIATEplus trial. Participants were treated twice-daily with BIAsp 30 over 24 weeks.. NCT00101751.. Efficacy endpoints included reductions in mean glycated hemoglobin (A1C) and fasting plasma glucose (FPG). Safety endpoints included hypoglycemia rates (events/patient-year) and adverse events. Body weight changes were also measured.. Glycemic control improved by a similar extent for all demographic groups. Observed mean decreases in A1C ranged from 2.4% to 2.6% after 24 weeks' treatment. Baseline-adjusted mean A1C decreases for White vs. Black/African-American subjects were 2.56% and 2.13% (p < 0.0001), and for Hispanic/Latino vs. non-Hispanic/Latino subjects were 2.45% and 2.42% (p = 0.677), respectively. Final FPG values were similar among all groups (141-146 mg/dL [7.83-8.10 m mol/L]), and baseline-adjusted FPG decreases were not significantly different (p > 0.025) between groups. Hypoglycemia was low for White, Black/African-American, Hispanic/Latino, and non-Hispanic/Latino subjects (0.08, 0.04, 0.03, and 0.07 major events/patient-year, with 0.60, 0.30, 0.37, and 0.52 minor events/patient-year, respectively). Body weight increases were 3.17 and 3.06 kg (White vs. African-American) and 2.69 and 3.19 kg (Hispanic/Latino vs. non-Hispanic/Latino). Final weight-adjusted total daily insulin doses were 0.60 U/kg for Black/African-American subjects vs. 0.78 U/kg for White subjects (p < 0.0001), and 0.71 U/kg for Hispanic/Latino subjects vs. 0.74 U/kg for non-Hispanic/Latino subjects (p = 0.42).. The trial was not designed or powered for comparisons across racial or ethnic groups, subjects were not stratified for pre-baseline medication regimens between each race and ethnic group, and unequal subject numbers and baseline A1C disparities existed between the pairs of groups being compared.. Diabetes self-management with BIAsp 30 using an easily followed self-titration algorithm produced low hypoglycemia rates. All subgroups achieved A1C reductions >2.1% and FPG declines >82 mg/dL that were similar across groups, demonstrating that self-titration of BIAsp 30 can successfully be pursued in a primary care setting by patients who had previously failed to meet ADA A1C targets under oral antidiabetes therapy, with race or ethnicity not an obstacle to achieving better glycemic control.

Topics: Biphasic Insulins; Black or African American; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Female; Hispanic or Latino; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; United States; White People

Insulin degludec/insulin aspart (IDegAsp) is a soluble co-formulation of insulin degludec (70%) and insulin aspart (IAsp: 30%). Here, we compare the efficacy and safety of IDegAsp, an alternative IDegAsp formulation (AF: containing 45% IAsp), and biphasic IAsp 30 (BIAsp 30).. Sixteen-week, open-label, randomised, treat-to-target trial.. Insulin-naive subjects with type 2 diabetes (18-75 years) and a HbA1c of 7-11% were randomised to twice-daily IDegAsp (n=61), AF (n=59) or BIAsp 30 (n=62), all in combination with metformin. Insulin was administered pre-breakfast and dinner (main evening meal) and titrated to pre-breakfast and pre-dinner plasma glucose (PG) targets of 4.0-6.0 mmol/l.. Mean HbA1c after 16 weeks was comparable for IDegAsp, AF and BIAsp 30 (6.7, 6.6 and 6.7% respectively). With IDegAsp, 67% of subjects achieved HbA1c 7.0% Without confirmed hypoglycaemia in the last 4 weeks of treatment compared with 53% (AF) and 40% (BIAsp 30). Mean fasting PG was significantly lower for IDegAsp vs BIAsp 30 (treatment difference (TD): -0.99 mmol/l (95% confidence interval: -1.68; 0.29)) and AF vs BIAsp 30 (TD: -0.88 mmol/l (-1.58; -0.18)). A significant, 58% lower rate of confirmed hypoglycaemia was found for IDegAsp vs BIAsp 30 (rate ratio (RR): 0.42 (0.23; 0.75)); rates were similar for AF vs BIAsp 30 (RR: 0.92 (0.54; 1.57)). IDegAsp and AF had numerically lower rates of nocturnal confirmed hypoglycaemia vs BIAsp 30 (RR: 0.33 (0.09; 1.14) and 0.66 (0.22; 1.93) respectively).. IDegAsp provided comparable overall glycaemic control to BIAsp 30 with a significantly lower rate of hypoglycaemia.

Topics: Adolescent; Adult; Aged; Biphasic Insulins; Chemistry, Pharmaceutical; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Combinations; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Insulin, Long-Acting; Male; Metformin; Middle Aged; Solubility; Treatment Outcome; Young Adult

To explore the safety and effectiveness of treatment with the insulin analogue, biphasic insulin aspart 30 (BIAsp 30), in people with type 2 diabetes mellitus (T2DM) in a subgroup of a Pakistani population from the A1chieve study.. A1chieve was a 24-week, international, prospective, multicentre, open label, observational, non-interventional study designed to evaluate the safety and clinical effectiveness of 66,726 people with T2DM who were initiated with basal insulin detemir, fast actinginsulin aspart, and BIAsp 30 (30% soluble insulin aspart, 70% protamine-crystallized insulin aspart). The study was conducted in 28 countries across Asia, Africa, Latin America, and Europe. Here, we report data from a subgroup of 762 people with T2DM from the Pakistani cohort (insulin naïve and insulin users) who were treated withpremix insulin (BIAsp 30) +/- oral antidiabetic drugs (OADs).. The decrease in HbAlc at week 24 was statistically significant in the entire cohort, the insulin naïve, and insulin users (1.7 +/- 1.1%, 1.8 +/- 1.3% and 1.7 +/- 0.9%, respectively, p<0.001 for all).There was a statistically significant decrease in the mean fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) from baseline toweek 24 in the entire cohort, in the insulin naïve and in the insulin users with BIAsp 30 treatment (p<0.001 for all).No major hypoglycaemic events were reported during the entire study period. There was a statistically significant decrease in the systolic blood pressure (SBP) in all groups (p<0.001). The improvement in the quality of life score (QoL)was statistically significant in all groups (p<0.001 for all).. BIAsp 30 treatment appeared to be well tolerated and effective as indicated byimproved glycaemiccontrol and QoL in people with T2DM in the Pakistani population after 24 weeks.

Topics: Adult; Biological Availability; Biphasic Insulins; Blood Glucose; Blood Pressure; Cholesterol; Diabetes Mellitus, Type 2; Drug Evaluation; Drug Monitoring; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Pakistan; Pharmacovigilance; Prospective Studies; Quality of Life; Treatment Outcome

This A1chieve® study subgroup analysis examined clinical safety and effectiveness of biphasic insulin aspart 30 (BIAsp30) ±OGLDs in 6323 individuals with T2D, switching from biphasic human insulin 30 (BHI30) ±OGLDs.. A1chieve was a 24-week, international, prospective, observational, multi-centre, open-label study in individuals with T2D starting treatment with BIAsp30, insulin detemir or insulin aspart as part of routine clinical care.. Mean baseline (SD) dose BHI was 0.56 (0.25) IU/kg. BIAsp30 was initiated at 0.57 (0.25) U/kg; the daily dose was 0.62 (0.28)U/kg by Week 24. Switching from BHI30 to BIAsp30 was associated with significant mean reduction in HbA1c of 1.7% [-18 mmol/mol] (1.6) from a baseline of 9.1% [76 mmol/mol] (p<0.001); FPG and PPG were also significantly reduced (p<0.001). Major hypoglycaemic episodes decreased from 0.69 events/patient/year at baseline to 0.03 events/patient/year at Week 24. Minor hypoglycaemia decreased from 5.31 to 2.04 events/patient/year from baseline to study-end. Five serious adverse drug reactions (hypoglycaemia) were reported by five individuals (0.1%). Mean bodyweight increased by 0.1 (3.3)kg from baseline to 24 weeks. Improved self-reported quality of life was observed.. Switching from BHI30 to BIAsp30 in individuals with T2D is associated with improvement in glycaemic control and reduced rates of hypoglycaemia, without tolerability or safety issues.

Topics: Adult; Africa, Northern; Aged; Asia; Biphasic Insulins; Cohort Studies; Diabetes Mellitus, Type 2; Drug Combinations; Drug Monitoring; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Middle East; Prospective Studies; Quality of Life

The aim of this study was to compare coefficient of variation of fasting capillary blood glucose (FBG) between insulin glargine and NPH in T2DM with poorly controlled by oral antidiabetic drugs. The results demonstrated that insulin glargine was more potent in improving glycemic control than NPH with stable FBG.

Topics: Adult; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Homeostasis; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Resistance; Insulin-Secreting Cells; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged

We compared basal regimens of glargine or NPH among insulin-naïve, U.S. inner city, ethnic minority type 2 diabetic patients who were sub-optimally controlled on maximally tolerated doses of combination oral agents.. Eighty-five subjects were randomized to 26 weeks of open-label, add-on therapy using single doses of bedtime NPH, bedtime glargine, or morning glargine; initially through an 8-week dose titration phase, followed by a 16-week maintenance phase during which insulin doses were adjusted only to avoid symptomatic hypoglycemia.. All three groups were comparable at baseline (mean HbA(1c) 9.3 ± 1.4%), and improved their HbA(1c) (to 7.8 ± 1.3%), fasting, and pre-supper glucose readings, with no significant between-group differences. Weight gain was greater with either glargine regimen (+3.1 ± 4.1 kg and +1.7 ± 4.2 kg) compared to NPH (-0.2 ± 3.9 kg), despite comparable total insulin doses. Pre-supper hypoglycemia occurred more frequently with morning glargine, but nocturnal hypoglycemia and improvements in treatment satisfaction did not differ among groups.. Among inner city ethnic minority type 2 diabetic patients in the U.S., we found no differences in basal glycemic control or nocturnal hypoglycemia between glargine and NPH, although glargine precipitated greater weight gain.

Topics: Adolescent; Adult; Aged; Blood Glucose; Circadian Rhythm; Cities; Diabetes Mellitus, Type 2; Ethnicity; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Maximum Tolerated Dose; Middle Aged; Minority Groups; Treatment Outcome; Weight Gain; Young Adult

To compare the pharmacokinetics and pharmacodynamics of NPH, glargine, and detemir insulins in type 2 diabetic subjects.. This study used a single-blind, three-way, cross-over design. A total of 18 type 2 diabetic subjects underwent a euglycemic clamp for 32 h after a subcutaneous injection of 0.4 units/kg at 2200 h of either NPH, glargine, or detemir after 1 week of bedtime treatment with each insulin.. The glucose infusion rate area under the curve(0-32 h) was greater for glargine than for detemir and NPH (1,538 ± 688; 1,081 ± 785; and 1,170 ± 703 mg/kg, respectively; P < 0.05). Glargine suppressed endogenous glucose production more than detemir (P < 0.05) and similarly to NPH (P = 0.16). Glucagon, C-peptide, free fatty acids, and β-hydroxy-butyrate were more suppressed with glargine than detemir. All 18 subjects completed the glargine study, but two subjects on NPH and three on detemir interrupted the study because of plasma glucose >150 mg/dL.. Compared with NPH and detemir, glargine provided greater metabolic activity and superior glucose control for up to 32 h.

Topics: Blood Glucose; Circadian Rhythm; Cross-Over Studies; Diabetes Mellitus, Type 2; Drug Administration Schedule; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

Acute hyperglycaemia exerts deleterious effects on the arterial wall. We suggested that rapid-acting insulin has a beneficial postprandial effect on endothelial dysfunction and inflammation compared with intermediate-acting insulin because of its ability to lower postprandial hyperglycaemia. This was tested in a parallel, controlled study on well-controlled patients with type 2 diabetes randomly assigned to bedtime Neutral Protamine Hagedorn (NPH) insulin (n = 41) or mealtime insulin aspart (n = 37). They were served standard diabetic meals for breakfast (8.00) and lunch (12.00). Blood samples were collected at 7.40 (fasting), 9.30, 11.30, 13.30 and 15.30 and analysed for glucose, insulin, lipids, intercellular adhesion molecules (ICAM), C-reactive protein (CRP), von Willebrand factor (vWF) and fibrinogen. The postprandial glucose response differed significantly between insulin regimens with a postprandial increase on NPH insulin and a decrease on insulin aspart. There was a minor but significant postprandial decrease in ICAM, CRP and vWF on both insulin regimens and a decrease in fibrinogen on NPH insulin. No insulin group differences were observed in postprandial responses for ICAM, CRP, vWF and fibrinogen. The rapid-acting insulin analogue aspart and the intermediate-acting insulin NPH had different effects on postprandial glucose response but similar postprandial effects on markers of inflammation and endothelial dysfunction.

Topics: Aged; Biomarkers; Cell Adhesion Molecules; Diabetes Mellitus, Type 2; Endothelial Cells; Female; Food Deprivation; Humans; Inflammation; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Postprandial Period; Sleep; von Willebrand Factor

To examine the effect of intensive glycemic control therapy (IT) on insulin sensitivity and β-cell function in newly diagnosed type 2 diabetic patients compared with subjects with normal glucose tolerance (NGT) and those with impaired glucose tolerance (IGT).. Forty-eight newly diagnosed type 2 diabetic patients were randomly assigned to IT for 2 weeks and followed up for 1 year. Intravenous glucose tolerance tests were conducted in NGT, IGT, and diabetic subjects. Blood glucose and insulin were measured before and after IT and at the 1-year follow-up.. IT lowered the homeostasis model assessment (HOMA) for insulin resistance (IR) significantly, from 3.12 ± 1.4 (mean ± SD) to 1.72 ± 0.8, a level comparable to the IGT (1.96 ± 1.1) and NGT (1.37 ± 0.6) subjects in the remission group; however, no HOMA-IR improvement was observed in nonremission subjects. HOMA-β in the remission group was improved (mean, interquartile range) from 18.4 (8.3-28.5) to 44.6 (32.1-69.1) and acute insulin response of insulin (AIRins) from 1.50 ± 0.22 to 1.83 ± 0.19 μIU/mL after IT, but was still significantly lower than those in NGT individuals (HOMA-β: 86.4 [56.7-185.2], P < 0.01; AIRins: 2.54 ± 0.39 μIU/mL, P < 0.01). After IT and at 1 year, the hyperbolic relationship between HOMA-β and HOMA sensitivity of remission subjects shifted close to that of IGT subjects.. IT in newly diagnosed type 2 diabetes not only partially restored β-cell function but also greatly restored insulin sensitivity. Compared with IGT and NGT subjects, β-cell function was less restored than insulin sensitivity after IT in the remission subjects.

Topics: Adult; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Insulin-Secreting Cells; Insulin, Isophane; Insulin, Regular, Human; Isophane Insulin, Human; Male; Middle Aged

To compare the blood glucose levels and variability of premixed insulin aspart (BIAsp 30) with human insulin premix (BHI 30) used in a twice a day injection regimen in elderly type 2 diabetes patients.. 52 cases of inadequate glycemia controlled by oral anti-diabetic drugs were randomly divided into two groups, treated on a twice-daily regimen with BIAsp 30 (n = 26) and BHI 30 (n = 26) respectively. After achieving the target goal, a continuous glucose monitoring system (CGMS) was used to compare the blood glucose levels, blood glucose fluctuant coefficient (BGFC), postprandial glucose excursion (PPGE), and occurrence of hypoglycemia.. BIAsp 30 was as effective as BHI 30 in control glycaemia. Detected by CGMS, there was no statistical differences in blood glucose levels among pre-three main meals, post-lunch and the mean blood glucose (MBG) (all P > 0.05). The BGFC levels were significantly lower in the BIAsp 30 group than in the BHI 30 group [(1.69 ± 0.42) mmol/L vs. (2.07 ± 0.51) mmol/L, t = -3.013, P < 0.01]. The blood glucose increment over breakfast, dinner and the percentage of time at hyperglycaemia (BG > 11.1 mmol/L) were lower in the BIAsp 30 group than in the BHI 30 group [(2.89 ± 1.32) mmol/L vs. (3.83 ± 1.18) mmol/L, t = -2.705, P < 0.01; (2.69 ± 1.37) mmol/L vs. (3.55 ± 1.40) mmol/L, t = -2.232, P < 0.05; (6.21 ± 6.04)% vs. (10.01 ± 6.80)%, t = -2.132, P < 0.05]. The frequency of hypoglycemia was lower in the BIAsp 30 group than in the BHI 30 group, but there was no statistical difference (P > 0.05).. Pre-meal injection of BIAsp 30 in a twice-daily regimen could significantly improve the control of postprandial glucose level and reduce the overall glucose excursions so as to lower the risk of hypoglycaemia when compared to BHI 30.

Topics: Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Humans; Insulin Aspart; Insulin, Isophane

To explore safety and efficacy of BIAsp 30 as initiation or replacement therapy in routine clinical practice in patients with poorly controlled diabetes in the Chinese cohort of the IMPROVE study.. In the 26-week, non-interventional, observational study, Chinese subjects with diabetes started BIAsp 30 treatment in routine care. Data from patients' diaries and medical records were transferred to CRFs by participating physicians.. NCT00659282.. Of the 21,729 subjects enrolled (mean age 54.0 years, BMI 24.6 kg/m 2 , diabetes duration 4.86 years), 32.3% were treatment-naïve, 59.3% were from oral anti-diabetic drugs (OADs) only and 8.1% were from insulin +/- OADs. Overall, mean HbA(1c) and FBG decreased by 2.82% and 5 mmol/L, respectively. In the subgroups, changes were: -3.27% and -6.06 mmol/L (treatment-naïve), -2.57% and -4.54 mmol/L (OADs only), -2.96% and 3.51 mmol/L (insulin +/- OADs) all p < 0.05. HbA(1c) < 7% was achieved by 71.4% of patients. Only 0.1% of subjects reported major hypoglycaemia and 73 SADRs were observed without significant difference compared to those at baseline. Body weight did not change significantly.. Regardless of previous treatments, insulin initiation or replacement with BIAsp 30 improved glycaemic control without increasing major hypoglycaemia or weight gain in Chinese patients with diabetes.

Topics: Biphasic Insulins; Cohort Studies; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Patient Satisfaction; Quality of Life; Treatment Outcome; Weight Gain

Good glycaemic control in patients with diabetes mellitus often requires insulin supplementation therapy. Recent developments of analogue insulin and premixed formulations have increased the therapeutic options for patients who need such therapy. This study aimed to retrospectively clarify appropriate treatment regimens according to age, body mass index (BMI) and duration of diabetes in Japanese patients with type 2 diabetes previously entered in an open-label, randomized trial that compared convenience-oriented biphasic insulin aspart 30 versus multiple injections of insulin aspart with or without NPH insulin.. Japanese insulin-naïve patients were randomized to receive either biphasic insulin aspart 30 twice daily or insulin aspart three times daily with or without multiple injections of NPH insulin for a treatment period lasting 6 months.. Reduction of glycosylated haemoglobin (HbA(1c)) at the end of 6 months was not different in the two treatment groups irrespective of BMI, age and duration of diabetes. However, the achievement rate of HbA(1c) <7.0% was significantly higher in patients with a BMI <25 kg/m2 in the multiple-injection group and tended to be higher in patients with a diabetes duration <10 years in the twice-daily injection group.. Twice-daily injections of biphasic insulin aspart 30 may be more suitable for obese patients whereas multiple injections of insulin aspart with or without NPH insulin may be preferable for those with a longer duration of diabetes.

Topics: Adult; Age Factors; Aged; Biphasic Insulins; Body Mass Index; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Injections; Insulin; Insulin Aspart; Insulin, Isophane; Middle Aged; Retrospective Studies; Time Factors

We compare the efficacy and safety of once-daily biphasic insulin aspart 70/30 (BIAsp 30) and insulin glargine in Asian subjects with type 2 diabetes inadequately controlled with oral anti-diabetic drugs (OADs). In a 26-week, open-labelled, randomised, parallel-group, multinational, multicentre, treat-to-target trial, 155 insulin-naïve Asian subjects were treated with either BIAsp 30 or insulin glargine, both in combination with metformin and glimepiride. Change in HbA(1c) at end of treatment with BIAsp 30 was superior to insulin glargine (BIAsp 30-glargine=-0.36%, 95% CI [-0.64; -0.07], p=0.015). Mean self-measured plasma glucose (SMPG) at bedtime was significantly lower with BIAsp 30 than insulin glargine (7.98+/-0.34 mmol/L vs. 9.16+/-0.33 mmol/L, p=0.0078). Incidences of minor and daytime hypoglycaemia were higher with BIAsp 30 than those with glargine, but the difference did not reach the statistical significance. No difference was seen in nocturnal hypoglycaemia. The incidence of adverse events was comparable between treatments, with low incidence of serious adverse events and major hypoglycaemia. Mean body weight increased slightly in both groups. In insulin-naïve Asian subjects with type 2 diabetes who are inadequately controlled with OADs, once-daily BIAsp 30 is superior to insulin glargine.

Topics: Administration, Oral; Adolescent; Adult; Asian People; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Dosage Forms; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; International Agencies; Male; Middle Aged; Treatment Outcome; Young Adult

Postprandial release of intact proinsulin (IP) is an independent marker for beta-cell dysfunction in patients with type 2 diabetes. This open-label, parallel-group, two-arm, pilot study compared the beta-cell protective effect of adding insulin glargine (GLA) vs. NPH insulin to ongoing metformin.. Overall, 28 insulin-naive type 2 diabetes subjects (mean +/- SD age, 61.5 +/- 6.7 years; diabetes duration, 9.8 +/- 6.5 years; HbA1c, 7.1 +/- 0.5%; BMI, 30.7 +/- 4.3 kg/m(2)) treated with metformin and sulfonylurea were randomized to add once-daily GLA or NPH at bedtime. At baseline and after 3 months, subjects received a standardized breakfast, lunch and dinner, with pre- and postprandial blood sampling to measure plasma IP, total insulin and blood glucose (BG).. Insulin dose after 3 months was comparable in both groups (GLA vs. NPH: 23.6 +/- 13.4 vs. 23.3 +/- 12.7; p = NS ). Both treatments significantly reduced fasting BG levels (GLA: 158 +/- 19 to 121 +/- 23 mg/dl; NPH: 156 +/- 34 to 119 +/- 29 mg/dl; both p < 0.01 vs. baseline). Fasting and postprandial BG levels did not differ between groups. IP levels decreased in both groups (p < 0.05 at all timepoints). Although IP release after breakfast did not differ between treatments, GLA induced a greater reduction in IP release after lunch (p = 0.08) and dinner (p = 0.04). Total plasma insulin levels did not differ between groups.. Adding basal insulin to metformin reduces postprandial beta-cell load. While GLA and NPH had comparable effects at breakfast, GLA reduces beta-cell stress more effectively at dinner, and with a trend at lunch, most probably because of its longer lasting pharmacodynamic profile.

Topics: Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin-Secreting Cells; Insulin, Isophane; Insulin, Long-Acting; Male; Metformin; Middle Aged; Pilot Projects; Postprandial Period

To evaluate glycemic variability associated with two different premixed insulin analogue formulations when used in a twice-daily regimen.. Subjects comprised type 2 diabetic patients aged 20-79 years, treated with twice daily premixed insulin or insulin analogue formulations. All subjects were hospitalized for 6 days and randomized to receive either Humalog Mix 25 (Mix 25) or Humalog Mix 50 (Mix 50). They were then crossed over to the other arm between day 3 and day 4 of the study. Continuous glucose monitoring (CGM) was performed on all subjects to examine the differences in glycemic variability.. Eleven type 2 diabetic patients were enrolled. No significant difference was found in 24-hour mean glucose values and their SDs, pre-meal glucose values, increases from pre-meal to peak glucose values, or time to peak glucose levels between either group. However, the mean glucose values observed during 0-8 hrs were significantly lower with Mix 25 compared to Mix 50 (128 vs. 147 mg/dL; p = 0.024).. The twice-daily Mix 25 regimen provided superior overnight glycemic control compared to the Mix 50 regimen in Japanese patients with type 2 diabetes. However, both twice-daily regimens with either Mix 25 or Mix 50 provided inadequate post-lunch glycemic control.. Current Controlled Trials UMIN000001327.

Topics: Adult; Aged; Asian People; Biomarkers; Biphasic Insulins; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Drug Administration Schedule; Energy Intake; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Japan; Male; Middle Aged; Monitoring, Ambulatory; Pilot Projects; Postprandial Period; Time Factors; Treatment Outcome; Young Adult

While evidenced-based guidelines promote glycated hemoglobin (HbA(1c)) targets <7.0% in order to reduce the long-term risk of diabetic complications, many individuals with type 2 diabetes do not achieve these targets. Fear of hypoglycemia provides a major barrier to improving blood glucose control as a result of delayed insulin initiation and failure to appropriately titrate insulin following initiation. Modern insulin analogs were designed to achieve improved blood glucose control with similar hypoglycemic risk compared with non-analog insulins (or similar blood glucose control with reduced hypoglycemic risk). While this has been demonstrated in randomized controlled trials, there is a need to confirm these findings in an everyday clinical setting. The A(1)chieve study will evaluate adverse events and effectiveness of premix (biphasic insulin aspart 30 [NovoMix 30]), basal (insulin detemir [Levemir]), and meal-time (insulin aspart [NovoRapid]) insulin analogs in people with type 2 diabetes in near-routine clinical practice. A(1)chieve is an international, prospective, multi-center, open-label, non-interventional, 24-week study of people with type 2 diabetes using an insulin analog. The study will recruit 60 000 people from 30 countries across four continents (Asia, Africa, South America, and Europe). The primary aim of the study is to assess the adverse event profile of the study insulins in routine clinical practice, including rates of hypoglycemia. In addition, effectiveness (HbA(1c), fasting plasma glucose, and postprandial plasma glucose) and patient quality of life outcomes will be measured. Comprehensive epidemiological data will be collected at baseline, including recent plasma glucose results and hypoglycemic episodes, prevalence of diabetes-related complications, and measures of current standards of care. Thus, A(1)chieve should provide important information about how insulin analogs perform in daily clinical practice.

Topics: Biphasic Insulins; Clinical Protocols; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; International Cooperation; Prospective Studies

This is a work aimed to investigate the efficacy and safety of the combination of metformin with glargine or with neutral protamine Hagedorn in treatment of type 2 diabetes mellitus. Sixty such patients with poor glycemic control by oral antidiabetic drugs were included and divided into group A and group B. Thirty patients in group A were treated with glargine and metformin, and the other 30 patients in group B were treated with neutral protamine Hagedorn and metformin for 12 weeks. Fasting plasma glucose (FPG), postprandial glucose(PPG) and HbA1c were measured before and after the treatment. Hypoglycemia was also noted. At the end of the study, the levels of FPG, PPG and HbAlc were significantly lower than the baseline levels in the two groups (P < 0.05). At the 12th week, the percentage of HbAlc < 7% in group A was 53.3% and that in group B was 40.0%; statistically, there was no significant difference (P > 0.05). After the end of the treatment, there was no significant difference in that the percentage of HbA1c < 7% was 70.6% in group A and 62.5% in group B; the two groups' HbA1c levels were > or = 7%-9% at the baseline (P > 0.05). No sigificant difference in respect to the incidence rate of hypoglycemia in the two groups was noted (P > 0.05). In the cases of type 2 diabetes mellitus with poor glycaemic control by oral antidiabetic drug, glucose and HbA1c can be lowered further by the combination of metformin with glargine or with neutral protamine Hagedorn, the incidence rate of hypoglycemia is low. Metformin plus glargine or plus neutral protamine Hagedorn is a safe and effective therapeutic choice for type 2 diabetes mellitus cases with poor glycaemic control; moreover, metformin plus neutral protamine is a cheaper and effective choice.

Topics: Aged; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Metformin; Middle Aged

The aim of study was to evaluate the safety and efficacy of insulin detemir as a basal insulin switching from neutral protamine Hagedorn insulin (NPH) and insulin glargine in patients with diabetes on an intensive insulin therapy regimen.. This 6-month multicentre, prospective, treat-to-target [glycosylated haemoglobin (HbA(1c) ) less than 6.5%] trial included 92 people with diabetes (61 type 1, 29 type 2 and two unknown diabetes types). Detemir was administered first with fixed dose and injection times and then adapted to optimal dose after 3 months.. Mean HbA(1c) (%) of all the subjects at months 4 to 6 of the study was improved compared with month 0 (7.34 ± 0.87, 7.28 ± 0.88, 7.25 ± 0.93 vs. 7.55 ± 1.18; p < 0.05 paired t-test). However, significant improvement was seen only among the patients who had previously used NPH as a basal insulin. Twice-daily injection of basal insulin increased among people in the type 1 previously injected insulin glargine. Total insulin dose increased in the type 1 glargine group. The mean body weight change in the highest quartile body mass index (BMI) group was from 70.7 to 69.3 kg over the 6 months. Quality of life (QoL) relating to the patients' glycaemic control tended to improve without a change in frequency of hypoglycaemia.. The results suggest that insulin detemir has a greater effect on glycaemic control in subjects with poor glycaemic control using NPH; can reduce or maintain body weight in obese patients; and obtains perceptive stability for patients with unstable glycaemic control.

Topics: Adult; Aged; Anti-Obesity Agents; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Obesity; Prospective Studies; Treatment Outcome; Weight Loss

Insulin analogues are widely used but few data exist comparing different analogue regimens. We compared two such regimens in type 2 diabetes mellitus (T2DM) uncontrolled by oral antidiabetic agents (OADs) with or without basal insulin.. In a 26-week multinational, multicentre, randomized treat-to-target trial, OADs were discontinued and subjects randomized to analogue basal-bolus therapy (insulin detemir once daily and insulin aspart mealtimes) or biphasic insulin aspart 30 (30% rapid-acting insulin aspart), twice daily. Insulin was titrated to targets for fasting, predinner and postprandial plasma glucose (PG), as appropriate.. Of 719 subjects, 92% completed the study; 58% achieved haemoglobin fraction A(1c) (HbA(1c)) < or =7.0%, with reductions of 1.56% (to 6.96%) with basal-bolus therapy and 1.23% (to 7.17%) with biphasic insulin aspart. Reduction with basal-bolus therapy was superior in the overall population by 0.23% (p = 0.0052), with no difference between regimens in insulin-naive patients. Major hypoglycaemia occurred in five basal-bolus patients (0.9%) and in no patients with biphasic insulin aspart. Incidence of minor hypoglycaemia was similar in both groups. All insulin doses increased during titration, with increase in lunchtime insulin aspart dose and equal distribution of breakfast and dinner biphasic insulin aspart doses. Insulin detemir remained once daily in 87% of patients.. Modern insulin analogue regimens, adjusted to PG targets, enable a majority of people with T2DM to reach HbA(1c)< or =7.0% after failure of OADs and OAD-basal insulin therapy. Insulin-treated patients may benefit more from transfer to analogue basal-bolus therapy, while insulin-naive individuals benefit equally well from the more convenient biphasic analogue regimen.

Topics: Aged; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome; Weight Gain

Studies comparing the use of basal bolus with insulin analogs vs. split-mixed regimens with human insulins in hospitalized patients with type 2 diabetes are lacking.. In a controlled multicenter trial, we randomized 130 nonsurgical patients with blood glucose (BG) between 140 and 400 mg/dl to receive detemir once daily and aspart before meals (n = 67) or neutral protamine Hagedorn (NPH) and regular insulin twice daily (n = 63). Insulin dose was started at 0.4 U/kg.d for BG between 140 and 200 mg/dl or 0.5 U/kg.d for BG 201-400 mg/dl. Major study outcomes included differences in mean daily BG levels and frequency of hypoglycemic events between treatment groups.. Glycemic control improved similarly in both groups from a mean daily BG of 228 +/- 54 and 223 +/- 58 mg/dl (P = 0.61) to a mean daily BG level after the first day of 160 +/- 38 and 158 +/- 51 mg/dl in the detemir/aspart and NPH/regular insulin groups, respectively (P = 0.80). A BG target below 140 mg/dl before meals was achieved in 45% of patients in the detemir/aspart group and 48% in the NPH/regular group (P = 0.86). During treatment, 22 patients (32.8%) in the detemir/aspart group and 16 patients (25.4%) in the NPH/regular group had at least one episode of hypoglycemia (BG < 60 mg/dl) during the hospital stay (P = 0.34).. Treatment with basal/bolus regimen with detemir once daily and aspart before meals results in equivalent glycemic control and no differences in the frequency of hypoglycemia compared to a split-mixed regimen of NPH and regular insulin in patients with type 2 diabetes.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Humans; Hypoglycemic Agents; Inpatients; Insulin; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Young Adult

This randomised, open-label, two-way cross-over study compared the coefficient of variance (CV) of fasting and postprandial blood glucose (FBG and PPBG) with insulin glargine (glargine) versus neutral protamine Hagedorn (NPH) insulin treatment in patients with Type 2 diabetes (T2DM). Patients (N=20) on oral antidiabetic drugs (OADs) were treated with NPH (at bedtime) or glargine (at dinnertime) for 12 weeks of each cross-over treatment period; OADs were continued. The FBG CV was calculated from self-monitored BG values and PPBG using venous blood samples, or continuous glucose monitoring system (CGMS). Both insulins provided similar improvements in glycaemic control; however, PPBG was significantly lower after a standard meal test (performed at 13:00 h the day after insulin injection) with glargine versus NPH (p=0.02). Thirteen versus 15 patients experienced >or=1 episode of hypoglycaemia with glargine versus NPH. The results suggest that glargine plus OADs is more effective in reducing PPBG fluctuations during the day than NPH plus OADs.

Topics: Administration, Oral; Aged; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Female; Glyburide; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Metformin; Middle Aged; Monitoring, Ambulatory; Pilot Projects

The IMPROVE observational study evaluated the safety profile and effectiveness of biphasic insulin aspart 30/70 (BIAsp 30) in patients with type 2 diabetes in routine practice in 11 countries.. Patients who initiated insulin therapy with, or switched existing insulin therapy to, BIAsp 30 in routine care were eligible for this 26-week, non-interventional observational study. Data on adverse events, hypoglycaemia and glycaemic parameters were obtained from patients' diaries and medical notes. Questionnaire-based patient treatment satisfaction was also measured. We report global results and, uniquely for a diabetes observational study, country-specific data.. A total of 52,419 patients were enrolled from three prestudy treatment groups: no pharmaceutical therapy (n = 8966, diabetes duration 2.0 years, baseline HbA1c 9.9%), oral antidiabetic drugs (OADs) only (n = 33,797, diabetes duration 7.4 years, baseline HbA1c 9.2%) and insulin +/- OADs (n = 9568, diabetes duration 10.4 years, baseline HbA1c 9.3%). At final visit, HbA1c, fasting and postprandial blood glucose were significantly reduced from baseline in all subgroups (no pharmaceutical therapy: -3.1%, -5.9 and -9.0 mmol/l, respectively; OADs-only: -2.1%, -4.1 and -6.1 mmol/l; insulin +/- OADs: -2.0%, -3.3 and -5.1 mmol/l). Major hypoglycaemia rates decreased in all subgroups; minor hypoglycaemia increased in the insulin-naïve groups. There was no mean weight gain across subgroups. Across all countries, glycaemic parameters and major hypoglycaemia were reduced; weight increases were seen in some countries. Treatment satisfaction increased in all subgroups and countries following BIAsp 30 therapy.. Initiating insulin with, or switching insulin therapy to, BIAsp 30 in routine care resulted in improved glycaemic control, reduced major hypoglycaemia and greater treatment satisfaction.

Topics: Aged; Biphasic Insulins; Diabetes Mellitus, Type 2; Epidemiologic Methods; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Patient Satisfaction; Treatment Outcome

To compare safety and efficacy of biphasic insulin aspart 70/30 (BIAsp 30) with exenatide in subjects with type 2 diabetes mellitus (T2DM) not achieving glycemic targets with metformin and sulfonylurea in a randomized, open-label, 24-week trial.. Subjects (N = 372, T2DM > 6 months, age > or = 18 and < or = 80 years, HbA1c > or = 8%, insulin naive not achieving glycaemic targets, receiving metformin and sulfonylurea) were randomized 1: 1: 1 to receive either BIAsp 30 QD (12 U before supper); BIAsp 30 BID (12 U divided equally between pre-breakfast and pre-supper); or exenatide (5 microg BID for 4 weeks and 10 microg BID thereafter). Efficacy (HbA1c, fasting plasma glucose [FPG]) and safety (adverse events and hypoglycemic episodes) were assessed.. Glycemic control achieved with both BIAsp 30 BID and BIAsp 30 QD was superior to that with exenatide (BIAsp 30 BID-exenatide: HbA1c difference -0.91% [95% CI: -1.23 to -0.59%] and BIAsp 30 QD-exenatide: difference: -0.67% [95% CI: -0.99 to -0.34%]). At the end of the study, more subjects achieved HbA1c < 7% and < or = 6.5% in the BIAsp 30 BID group than in the exenatide group (HbA1c < 7%: 37% vs. 20%, p = 0.0060; HbA1c < or = 6.5%: 25% vs. 8%, p = 0.0004, respectively). Combined hypoglycemic episodes (major, minor, symptoms only) were reported by 56%, 61%, and 29% of the subjects in the BIAsp 30 QD, BIAsp 30 BID, and exenatide groups, respectively. Weight gain was observed in the BIAsp 30 group (BIAsp 30 QD: 2.85 kg, BIAsp 30 BID: 4.08 kg) and weight loss was observed in the exenatide group (-1.96 kg). Nausea or vomiting was responsible for discontinuation of seven subjects in the exenatide group and one subject in the BIAsp 30 BID group.. Significantly more T2DM patients (poorly controlled with combination metformin/sulfonylurea) achieved glycemic goals when treated with BIAsp 30 than with exenatide. The high baseline HbA1c values (approximately 10.2%) and the long duration of diabetes (approximately 9 years) suggests that some subjects may have been in an advanced stage of their diabetes and may not have had sufficient beta-cell function for a GLP-1 mimetic to be effective. The insulin-treated groups had more minor hypoglycemic events and weight gain but less gastrointestinal side-effects. In summary, BIAsp 30 was more efficacious in helping patients with high baseline HbA1c achieve glycemic goals.. www.clinicaltrials.gov, NCT00097877.

Topics: Adult; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Exenatide; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Metformin; Middle Aged; Peptides; Sulfonylurea Compounds; Venoms

IMPROVE is an open-label, multinational, non-randomised, 26-week observational study designed to evaluate the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) in routine clinical practice. Here, we report data for patients switching to BIAsp 30 from human premixed insulin.. Patients (n = 3856) with type 2 diabetes previously receiving human premixed insulin with or without oral antidiabetic drugs were eligible for inclusion. Demographic data, efficacy end-points (HbA(1c), fasting blood glucose and postprandial blood glucose) and safety end-points (serious adverse drug reactions, hypoglycaemia and adverse events) were collected at baseline and final visit. A subgroup analysis of mean dose change was also undertaken.. Switching patients to BIAsp 30 resulted in significant improvements in glycaemic control combined with a reduced risk of hypoglycaemia. Patients who reached the HbA(1c) target (< 7%) had shorter diabetes duration, lower HbA(1c) at baseline and needed less insulin. Over 30% of patients were able to reach this target without experiencing hypoglycaemia over the 26-week period. Compared with asymmetric dose switching, unit-for-unit switching resulted in the highest proportion of patients reaching HbA(1c) target and incurred the least amount of dose titration.. A unit-for-unit switch is the most effective as well as the simplest approach when transferring patients from biphasic human insulin 30 to BIAsp 30.

Topics: Aged; Biphasic Insulins; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Patient Satisfaction; Risk Factors; Treatment Outcome

The IMPROVE study is an openlabel, nonrandomized, observational study aimed at determining the safety and efficacy of biphasic insulin aspart 30 (BIAsp 30) treatment in subjects with type 2 diabetes from 11 countries. Here, we report the baseline data of the Indian cohort.. All subjects with type 2 diabetes requiring insulin and considered suitable for BIAsp 30 therapy based on their physician's clinical judgment were eligible to enter the study. The data recorded at baseline included demographic characteristics, detailed medical histories, physician-cited reasons for starting BIAsp 30 treatment, and the chosen dosage regimens.. The Indian cohort included 17,995 subjects with diabetes. Poor glycemic control (glycated hemoglobin [HbA(1c)], 8.7%-9.6%) was observed at baseline in all four geographical zones (North, South, East, and West) and prestudy treatment groups (no therapy, only oral antidiabetic drug [OAD], OAD +/- insulin, and OAD +/- insulin +/- BIAsp 30). Prevalence of both micro- and macrovascular complications was high, also reflecting poor glycemic control. Improving HbA(1c) and fasting and postprandial blood glucose levels were the most common reasons for starting BIAsp 30 therapy. The subjects were prescribed a mean BIAsp 30 dose of approximately 24 IU, and a twice-daily regimen was employed in almost 80% of subjects.. The baseline results of the IMPROVE study Indian cohort confirm the poor glycemic control and the delayed initiation and/or inadequacy of treatment in subjects with type 2 diabetes. These results also highlight the need for timely and appropriately intensive insulin-based therapy.

Topics: Aged; Biphasic Insulins; Blood Glucose; Body Mass Index; Cohort Studies; Demography; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; India; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Patient Satisfaction

Patients with type 2 diabetes (T2DM) have an increased mortality rate primarily because of macrovascular disease. Where T2DM patients cannot be managed sufficiently through diet, exercise and peroral antidiabetic drugs, that is when haemoglobin A1c (HbA1c) is above 7.0%, it is yet unknown whether a combination of metformin and insulin analogues is superior to insulin analogues alone. Nor is it known which insulin analogue regimen is the optimal.. The primary objective of this trial is to evaluate the effect of an 18-month treatment with metformin vs. placebo in combination with one of three insulin analogue regimens, the primary outcome measure being carotid intima-media thickness (CIMT) in T2DM patients.. A randomized, stratified, multicentre trial having a 2 x 3 factorial design. The metformin part is double masked and placebo controlled. The insulin treatment is open. The intervention period is 18 months.. Nine hundred and fifty patients with T2DM and HbA1c > or = 7.5% on treatment with oral hypoglycaemic agents or on insulin treatment and deemed able, by the investigator, to manage once-daily insulin therapy with a long-acting insulin analogue.. Central randomization stratified for age (above 65 years), previous insulin treatment and treatment centre.. Metformin 1 g x two times daily vs. placebo (approximately 475 patients vs. 475 patients) in combination with insulin detemir before bedtime (approximately 315 patients) or biphasic insulin aspart 30 before dinner with the possibility to increase to two or three injections daily (approximately 315 patients) or insulin aspart before the main meals (three times daily) and insulin detemir before bedtime (approximately 315 patients). Intervention follows a treat-to-target principle in all six arms aiming for an HbA1c < or = 7.0%.. Primary outcome measure is the change in CIMT from baseline to 18 months. Secondary outcome measures comprises the composite outcome of death, acute myocardial infarction, stroke or amputation assessed by an adjudication committee blinded to intervention, other cardiovascular clinical outcomes, average postprandial glucose increment from 0 to 18 months, hypoglycaemia and any inadvertent medical episodes. In addition, change in plaque formation in the carotids, HbA1c, cardiovascular biomarkers, body composition, progression of microvascular complications and quality of life will be assessed as tertiary outcome measures. TIME SCHEDULE: Patient enrolment started May 2008. Follow-up is expected to finish in March 2011.. CIMT is designed to provide evidence as to whether metformin is advantageous even during insulin treatment and to provide evidence regarding which insulin analogue regimen is most advantageous with regard to cardiovascular disease.

Topics: Adult; Aged; Biphasic Insulins; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Epidemiologic Methods; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Metformin; Middle Aged; Research Design; Treatment Outcome; Tunica Intima; Tunica Media; Young Adult

This 3-month study compared the effect on overall glycemic control of adding biphasic insulin aspart 30 (BIAsp30) and premixed human insulin 30/70 (BHI30) to metformin (met) in insulin-naïve, obese patients (30 males/20 females) with Type 2 diabetes (T2DM). MATERIAL/SUBJECTS: At baseline, patients had a mean age of 58.7 yr, glycated hemoglobin (HbA1c) 9.5%, and body mass index 34+/-2 kg/m2. Patients received either twice-daily BIAsp30 (no.=20) or twice-daily BHI30 (no.=30), and continued to receive maximal doses (2000 mg) of met for the duration of the study, but sulphonylurea oral antidiabetic drugs were discontinued. Primary efficacy endpoint was the change in HbA1c in both groups at study end. Safety endpoints included hypoglycemic episodes and weight gain.. Both groups reduced HbA1c by end of trial: BIAsp30 + met by 2.5% [2.16-2.86%; 95% confidence interval (CI)]; BHI30 + met by 1.18% (0.98- 1.39%; 95% CI), giving a significantly better HbA1c reduction with BIAsp30 + met (1.33%; p<0.05). Post-prandial plasma glucose decreased in both groups, by 6.38 mmol/l in patients treated with BIAsp30 + met, and by 4.34 mmol/l in those treated with BHI30 + met (p<0.05). Fasting plasma glucose also decreased in both groups, with a slightly larger decrease seen in BIAsp30 patients than in BHI30 patients (7.36 mmol/l at end of study vs 7.82 mmol/l; p=ns). Subjects treated with BIAsp30 gained less weight than those receiving BHI30 (0.3+/-0.1 kg vs 1.2+/-0.4 kg). There was no significant difference in the frequency or number of hypoglycemic episodes between groups.. Adding BIAsp30 to met in obese patients with T2DM results in better glycemic control and less weight gain than adding BHI30.

Topics: Aged; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged

To evaluate clinical efficacy and safety of biphasic insulin aspart (BIAsp) 30 twice daily (b.i.d.) vs. BIAsp 50 or BIAsp 70 (high-mix regimens) thrice daily (t.i.d.) all in combination with metformin in a 36-week clinical trial in subjects with type 2 diabetes.. Efficacy measurements included haemoglobin A(1c) (HbA(1c)) and eight-point plasma glucose (PG); safety included adverse events (AEs) and hypoglycaemic episodes. The three treatment groups (approximately 200 subjects in each group) were well matched regarding sex ratio, ethnicity, age and body mass index.. After 12 weeks, 43% and 54% in the BIAsp 50 and 70 groups, respectively, switched their dinner insulin to BIAsp 30. Both high-mix regimens were non-inferior to BIAsp 30 b.i.d., as measured by change in HbA(1c), and the BIAsp %50 regimen was superior. The odds for meeting the American Diabetes Association and The American Association of Clinícal Endocrinologist HbA(1c) targets of <7% and < or =6.5%, respectively, were significantly higher with the BIAsp 50 regimen than with BIAsp 30. A significantly lower PG level was achieved from lunch until 02:00 hours with both high-mix regimens compared with BIAsp 30 b.i.d. AEs were mild or moderate with all three regimens. Frequency of hypoglycaemic episodes was comparable for the BIAsp 50 and the BIAsp 30 b.i.d. regimens but was significantly higher with BIAsp 70 t.i.d.. Glycaemic control improved with BIAsp 50 t.i.d. without higher incidence of hypoglycaemia compared with BIAsp 30 b.i.d.; with BIAsp 70 t.i.d. lower PG levels from lunch to 02.00 hours, but more hypoglycaemic episodes were obtained compared with BIAsp 30 b.i.d.

Topics: Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Europe; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Metformin; Middle Aged; Treatment Outcome

The international IMPROVE observational study investigated the safety profile and effectiveness of biphasic insulin aspart 30/70 (BIAsp 30) in the routine treatment of patients with type 2 diabetes. We present analyses for the subgroup of patients who switched from basal insulin to BIAsp 30.. Patients in routine care who started insulin therapy with or switched to BIAsp 30 from existing insulin regimens were eligible for this 26-week study. This analysis includes only patients previously treated with basal insulin. Outcomes including adverse events, hypoglycaemic events and glycaemic profile were recorded from patients' notes, recall and diaries.. Of the 748 patients included (age 59.7+/-11.8 years, diabetes duration 11.4+/-7.3 years, baseline HbA1c 9.1+/-1.6%), 497 were previously using human neutral protamine Hagedorn (NPH) insulin and 245 analogue basal insulin. Overall, major and minor hypoglycaemia rates decreased from baseline to final visit (major: 0.171 to 0.011; minor: 9.70 to 5.89 events/patient-year) and were similar between the subgroups. HbA1c and fasting blood glucose were significantly reduced from baseline (NPH prestudy: -1.6%, -2.4 mmol/l; analogue basal prestudy: -1.8%, -2.4 mmol/l), as was postprandial blood glucose, with 33.8% of patients achieving the HbA1c target < 7% without hypoglycaemia. Insulin dose increased slightly from prestudy (0.33+/-0.21 U/kg), baseline (0.40+/-0.20 U/kg) to final visit (0.52+/-0.26 U/kg); most patients (76%) followed a twice-daily regimen at final visit. Body weight did not change significantly and treatment satisfaction increased.. Patients with type 2 diabetes inadequately controlled on basal insulins may improve their glycaemic control by intensification to BIAsp 30 therapy.

Topics: Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Patient Satisfaction; Treatment Outcome

This long-term study was designed to further characterise the retinal safety profile of insulin glargine and human neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes mellitus.. An open-label, 5 year, randomised (1:1), multicentre, stratified, parallel-group study conducted in the USA and Canada enrolled individuals with type 2 diabetes and either no or non-proliferative retinopathy (less than severe; Early Treatment Diabetic Retinopathy Study [ETDRS] level less than 53 in both eyes) who were treated with oral hypoglycaemic agents (OHAs) alone, insulin alone or OHAs with insulin for >/=3 months prior to study entry and a baseline HbA(1c) level of 6.0-12.0%. Patients were randomised by the investigator according to the centralised interactive voice response system to receive twice-daily NPH insulin (n = 509) or once-daily basal insulin glargine (n = 515). The investigator was not blinded to the treatment group to which each participant had been assigned. The main objective of this study was to compare the progression of diabetic retinopathy between treatment groups by analysing the percentage of patients with three or more step progression in the ETDRS retinopathy patient-level severity scale after treatment with either basal insulin. Masked, centralised grading of seven-field stereoscopic fundus photographs was used.. Similarly sustained glycaemic control was observed in both the insulin glargine and NPH insulin treatment groups. Despite a slightly greater severity of diabetic retinopathy for the insulin glargine group at baseline, three or more step progression in ETDRS score from baseline to end-of-study was similar between treatment groups (14.2% [53/374] of insulin glargine-treated patients vs 15.7% [57/363] of NPH-treated patients); the difference in the incidence of progression was -1.98% (95% CI -7.02, 3.06%). Other measures of retinopathy-the development of proliferative diabetic retinopathy and progression to clinically significant macular oedema-occurred to a similar degree in both treatment groups. No other safety issues, such as unexpected adverse events for either insulin emerged during the 5 year study. However, NPH insulin treatment was associated with a higher incidence of severe hypoglycaemia compared with insulin glargine.. This study shows no evidence of a greater risk of the development or progression of diabetic retinopathy with insulin glargine vs NPH insulin treatment in patients with type 2 diabetes mellitus.. ClinicalTrials.gov NCT00174824. This study was sponsored by sanofi-aventis.

Topics: Aged; Blood Glucose; Canada; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Disease Progression; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Internationality; Male; Middle Aged; Patient Selection; United States

To compare blood glucose control when using biphasic insulin aspart (BIAsp) three times a day (using 70/30 high-mix before breakfast and lunch), with biphasic human insulin (BHI, 30/70) twice daily in adults with type 2 diabetes already treated with insulin.. In a 60-day, open-label, crossover study, people with insulin-treated type 2 diabetes [n = 38, baseline haemoglobin A1c 8.3 +/- 0.9 (s.d.) %] were randomized to BIAsp three times a day before meals, as BIAsp 70 (70% insulin aspart and 30% protamine-complexed insulin aspart) before breakfast and lunch and BIAsp 30 (30/70 free and protamine-complexed insulin aspart) before dinner, or to human premix insulin (BHI) 30/70 twice a day before meals. A 24-h in-patient plasma glucose profile was performed at the end of each 30-day treatment period. The total daily insulin dose of BIAsp regimen was 110% of BHI and the doses were not changed during the study.. There was no difference between BIAsp and BHI in geometric weighted average serum glucose over 24 h [7.3 vs. 7.7 mmol/l, BIAsp/BHI ratio 0.95 (95% CI 0.88-1.02), not significant (NS)], but daytime geometric weighted average glucose concentration was significantly lower with the BIAsp regimen than with BHI [8.3 vs. 9.2 mmol/l, BIAsp/BHI ratio 0.90 (0.84-0.98), p = 0.014]. The mealtime serum glucose excursion was also lower with BIAsp than with BHI with statistically significant differences at lunchtime [difference -4.9 (-7.0 to -2.7) mmol/l, p = 0.000); the difference in glucose excursions above 7.0 mmol/l was also significant [-5.8 (-8.3 to -3.2) mmol/l, p = 0.000). The proportion of participants experiencing confirmed hypoglycaemic episodes was similar between regimens (42 vs. 43%, NS).. An insulin regimen using high-mix BIAsp (BIAsp 70) before breakfast and lunch and BIAsp 30 before dinner can achieve lower blood glucose levels during the day through reduced mealtime glucose excursions in particular at lunchtime than a twice-daily premix regimen.

Topics: Adult; Aged; Biphasic Insulins; Blood Glucose; C-Peptide; Cross-Over Studies; Diabetes Mellitus, Type 2; Drug Administration Schedule; England; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Treatment Outcome; Young Adult

Topics: Diabetes Mellitus, Type 2; Diabetic Retinopathy; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Neoplasms; Risk Factors

Topics: Biphasic Insulins; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Treatment Outcome

To assess the efficacy and safety of biphasic insulin aspart 70/30 (BIAsp 30) and insulin glargine, administered once daily in subjects with type 2 diabetes inadequately controlled with oral anti-diabetic drugs.. In this 26-week, open-labeled, randomized, parallel-group, multinational, treat-to-target trial, 480 insulin-naïve subjects were randomized to receive either BIAsp 30 before dinner or insulin glargine at bedtime, both in combination with metformin and glimepiride.. NCT00469092, ClinicalTrials.gov.. A total of 433 subjects completed the trial. Estimated mean reduction in HbA(1c) from baseline to end of treatment was -1.41% with BIAsp 30 and -1.25% with insulin glargine (BIAsp 30 - insulin glargine = -0.16%, 95% CI [-0.30; -0.02], p = 0.029). At the end of treatment, mean HbA(1c) was 7.1% and 7.3% for BIAsp 30 and insulin glargine, respectively. Significantly lower plasma glucose levels were observed with BIAsp 30 post-dinner (BIAsp 30 - insulin glargine = -0.52 mmol/L, 95% CI [-1.02; -0.03], p = 0.04) and at bedtime (BIAsp 30 - insulin glargine = -0.78 mmol/L, 95% CI [-1.25; -0.31], p < 0.01). The relative risk (RR) of experiencing a nocturnal hypoglycemic episode (00:00-06.00 a.m.) was significantly higher with BIAsp 30 than with insulin glargine (1.1 versus 0.5 episodes/year, RR = 2.41, 95% CI [1.34; 4.34], p = 0.003), but overall hypoglycemia rates were low. There were three major hypoglycemic episodes in each group.. With respect to HbA(1c), BIAsp 30 fulfilled the statistical criteria for non-inferiority and superiority to insulin glargine and, according to pre-defined criteria, the improvements in HbA(1c) are considered clinically equivalent. Subjects had an increased risk of minor nocturnal hypoglycemia with BIAsp 30. There were no differences in treatment satisfaction between the two groups.

Topics: Administration, Oral; Aged; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Dosage Forms; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Treatment Failure

To compare the efficacy and safety of insulin aspart (IAsp) and human insulin (HI) when applied as meal-time insulin with neutral protamine Hagedorn insulin (NPH) at bedtime in diabetics.. A total of 220 Chinese subjects with type 1 or type 2 diabetes from 5 different hospitals were randomized by a ratio of 1:1 into two groups accepting IAsp or HI combined with NPH respectively. The main endpoints were assessed by fasting plasma glucose (FPG), 2 hour postprandial plasma glucose (2 h PPG), HbAlc and hypoglycemia.. A greater reduction in mean 2 h PPG was achieved in the IAsp group [(14.6 +/- 5.3) mmol/L] as compared with the HI group [(8.4 +/- 4.1) mmol/L] (P < 0.01, adjusted for baseline value, center effect and diabetes type). Significantly more IAsp-treated subjects reached the 2 h PPG target (50.0% vs 25.5%, P < 0.01). HbA1c was reduced more in IAsp/NPH group [(9.3 +/- 1.4)% vs (7.7 +/- 1.3)%] than in HI/NPH group [(9.2 +/- 1.2)% vs (7.7 +/- 1.2)%]. HbA1c target was reached by 24.5% (IAsp) vs 14.5% (HI) of subjects (P < 0.05). No major hypoglycemia or serious adverse events were observed for the IAsp group. Lower incidence of nocturnal hypoglycemia (IAsp/NPH: 3% vs HI/NPH: 4%) was reported in the IAsp group. Average daily insulin doses were 0.60/0.23 (IAsp/NPH) and 0.65/0.24 (HI/NPH) IU/kg respectively.. Treatment of IAsp in basal-bolus therapy in combination with NPH provides a superior postprandial glucose control and allows more subjects to reach the glycemic target without elevating the nocturnal hypoglycemic risk or adverse events.

Topics: Adolescent; Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Postprandial Period; Protamines; Young Adult

Diabetes is a debilitating chronic illness having multiple impacts on physical and mental well-being of patients. When treating chronic conditions like diabetes, psychosocial aspects and quality of life (QoL) have to be considered; however, these receive less attention due to various reasons. Patients with diabetic complications have increased levels of depression and decreased QoL This necessitates evaluating QoL of patient which now is used as a primary or secondary end point in clinical trials eg, Diab-MedSat QoL questionnaire used in diabetes. At some point all diabetic patients may require insulin to control hyperglycaemia and disease progression. The traditional insulin syringe and needle delivery system has been the principal barrier in the treatment of diabetes as it was not well accepted among the patients due to various reasons. A success over this approach has been pen like devices like FlexPen and Novopen3 which are becoming more popular than the conventional syringe-and-needles as they have several advantages like, easy to carry, use, maintain and also reduces administrative errors ensuring accurate doses are delivered. The objective of IMPROVE study is to evaluate the safety and effectiveness of biphasic insulin aspart (NovoMix 30) in normal clinical practice conditions, in India. This is an open label, non-randomised, non-interventional, observational, safety and effectiveness study in approximately 17,995 patients with type 2 diabetes mellitus. A cohort of Indian patients (n = 349) from all 4 geographical locations (North, West, East and South of India) were administered QoL instrument Diab-MedSat at baseline and 346 patients at final visit (n = 346) to assess their satisfaction with the treatment they received. The results were included in the final statistical analysis as additional outcome variables. The Diab-MedSat Novo Nordisk June 2004 English (UK) version is used. The Diab-MedSat has 21 items that need to be answered and it is scored as an overall score (all 21 items) as well as three subscale scores regarding burden (11 items), symptoms (5 items), efficacy (5 items). The complete analysis took into account all 21 items of Diab-MedSat questionnaire with their subscales. Analyses of the cohort showed higher patient satisfaction among the patients administered Diab-MedSat questionnaire from baseline (n = 349) to final visit (n = 346). The mean of overall score was 52.33 (baseline visit) versus 79.03 (final visit). The difference in th

Topics: Biphasic Insulins; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; India; Insulin; Insulin Aspart; Insulin, Isophane; Male; Patient Compliance; Patient Satisfaction; Quality of Life; Surveys and Questionnaires

Efficacy and safety of biphasic insulin aspart (BIAsp 30, 30% short-acting and 70% intermediate-acting insulin aspart) added to an optimized treatment of metformin and pioglitazone (met/pio) were compared with treatment with optimized met/pio in type 2 diabetes patients.. This randomized, 34-week, parallel-group study enrolled insulin-naive, type 2 diabetes patients (HbA(1c) 7.5-12.0%) previously using two oral antidiabetic (OAD) agents. During an 8-week run-in period, treatment was changed to met/pio and doses were adjusted up to 2500 mg/day and 30 or 45 mg/day respectively. Subjects either continued met/pio alone or added BIAsp 30 initiated at 6 units twice daily and titrated to target plasma glucose (PG) (4.4-6.1 mmol/l).. At end-of-study, subjects treated with BIAsp 30+met/pio (n = 93) had a mean (+/-s.d.) HbA(1c) reduction significantly greater than treatment with met/pio (n = 88) (1.5% +/- 1.1 vs. 0.2% +/- 0.9, p < 0.0001 between groups). Subjects treated with BIAsp 30+met/pio were more likely to reach The American Association of Clinical Endocrinologists and European Association for the Study of Diabetes/American Diabetes Association HbA(1c) targets of < or =6.5 and <7.0%, respectively, than with met/pio only (HbA(1c)< or =6.5%: 59 vs. 12%; HbA(1c) <7.0%: 76 vs. 24%). At end-of-study, self-monitored glucose profile values at all eight daily time points were significantly less for the BIAsp 30+met/pio group compared with the met/pio group, and minor hypoglycaemia (defined as PG < 3.1 mmol/l) was more frequent (8.3 vs. 0.1 events/year, p < 0.001). Both groups gained weight during treatment (BIAsp 30+met/pio, 4.6 +/- 4.3 kg; met/pio, 0.8 +/- 3.2 kg; p < 0.001).. Addition of insulin in type 2 patients treated with met/pio is an effective way to achieve glycaemic targets. Treatment with BIAsp 30+met/pio achieved significantly greater reduction in HbA(1c), as compared with met/pio alone. In patients with type 2 diabetes poorly controlled by 2 OADs, more achieved glycaemic targets using BIAsp 30+met/pio than using met/pio alone.

Topics: Adult; Aged; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Metformin; Middle Aged; Pioglitazone; Thiazolidinediones; Treatment Outcome; Young Adult

To evaluate the efficacy, safety and treatment satisfaction with biphasic insulin aspart 30 (BIAsp30) in elderly patients with type 2 diabetes.. The Physicians' Routine Evaluation of Safety and Efficacy of NovoMix 0 Therapy Korea study was a 6-month, prospective, observational study. No study-specific interventions were involved except the collection of data. All patients with type 2 diabetes not adequately controlled on their previous therapy, and who were prescribed BIAsp30 as monotherapy, or in combination with oral hypoglycaemic agents, were eligible for the study. This subgroup analysis was based on the outcomes in patients > or years (n = 1720).. BIAsp30 treatment was associated with significant mean reductions in haemoglobin A1c, fasting plasma glucose and post-prandial plasma glucose levels of 1.2 +/- 1.6%, 2.3 +/- 3.5 mmol/l and 4.8 +/- 5.3 mmol/l at 6 months (p < 0.0001 for all), from baseline levels of 9.1 +/- 1.7%, 10.7 +/- 3.4 mmol/l and 16.7 +/- 5.0 mmol/l, respectively. The rate of hypoglycaemia declined from 3.02 to 1.31 episodes per patient year, between baseline and study end. The proportion of patients reporting adverse drug reactions was low (0.3 and 0.1% at 3 and 6 months, respectively). Body weight gain was mild at <0.1 kg at 3 months, and 0.3 kg at 6 months. As compared to the previous treatment, >80% of patients were rated as being either 'very satisfied' or 'satisfied' with BIAsp30 treatment.. In this subanalysis of Korean elderly patients with type 2 diabetes inadequately controlled on their previous therapies, treatment with BIAsp30 offered improvements in glycaemic control and was well tolerated. Body weight gain was minimal with BIAsp30, and treatment satisfaction among these patients appeared to be high.

Topics: Adult; Aged; Biphasic Insulins; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Patient Satisfaction; Postprandial Period; Prospective Studies; Treatment Outcome

PRESENT (Physicians' Routine Evaluation of Safety and Efficacy of NovoMix 30 Therapy) is the largest, multinational, open-labelled, uncontrolled and completed observational study of the efficacy and safety of biphasic insulin aspart 30 (BIAsp 30) treatment in clinical practice. We present results of 3 months of treatment in Chinese patients with type 2 diabetes mellitus who were inadequately controlled on current treatment.. Patients received BIAsp 30 treatment with or without oral antidiabetic drugs (OADs). Patients were categorized according to their treatment prior to entering the study: drug-naive (n = 3697), OAD (n = 4754), insulin (n = 2392) or OAD + insulin (n = 817).. At 3 months, significant reductions from baseline were observed in the mean haemoglobin A(1c) (HbA(1c)) (-2.24 +/- 1.67, -2.04 +/- 1.57, -1.82 +/- 1.49 and -1.86 +/- 1.61%), fasting plasma glucose (-3.93 +/- 3.12, -3.51 +/- 2.55, -2.99 +/- 2.93 and -3.38 +/- 3.16 mmol/l) and postprandial plasma glucose (-7.09 +/- 4.92, -6.51 +/- 4.02, -5.20 +/- 4.31 and -5.50 +/- 4.32 mmol/l) in the drug-naive, OAD, insulin and insulin + OAD groups respectively (p < 0.001). The proportions of patients in each group achieving target HbA(1c) of less than 7% were higher at 3 months (49.5, 51.8, 51.0 and 48.3%) compared with baseline (3.2, 4.2, 7.1 and 8.3%). The rates of hypoglycaemic episodes (events per patient-year) were lower at the end of the study in all the groups compared with baseline. Hypoglycaemic episodes were mostly minor and diurnal in nature. A total of 151 adverse drug reactions were reported, of which five were serious adverse drug reaction (SADRs). These SADRs were all symptoms of local hypersensitivity.. The use of BIAsp 30 monotherapy or in combination with OADs in clinical practice was efficacious and safe in Chinese patients with poorly controlled type 2 diabetes.

Topics: Adult; Aged; Biphasic Insulins; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Prospective Studies; Treatment Outcome

Insulin glargine is a long-acting human insulin analog often administered at bedtime to patients with type 2 diabetes. It reduces fasting blood glucose levels more efficiently and with less nocturnal hypoglycemic events compared with human neutral protamine Hagedorn (NPH) insulin. Therefore, bedtime injections of insulin glargine and NPH insulin were compared overnight and in the morning.. In 10 type 2 diabetic patients, euglycemic clamps were performed, including [6,6'](2)H(2) glucose, to study the rate of disappearance (Rd) and endogenous production (EGP) of glucose during the night. On separate days at bedtime (2200 h), patients received a sc injection of insulin glargine, NPH insulin, or saline in a randomized, double-blind fashion.. Similar doses of both insulins had different metabolic profiles. NPH insulin had a greater effect on both Rd and EGP in the night compared with insulin glargine. By contrast, in the morning, insulin glargine was more effective, increasing Rd by 5.8 micromol/kg(-1).min(-1) (95% confidence interval 4.7-6.9) and reducing EGP -5.7 (-5.0 to -6.4) compared with NPH insulin. Nearly 80% of the glucose lowering effect in the morning was due to insulin glargine's reduction of EGP. Its injection was associated with one-third lower morning glucagon levels compared with NPH insulin (P = 0.021).. Nocturnal variations of EGP and Rd explain the reduced incidence of hypoglycemia and lower fasting glucose levels reported for insulin glargine compared with human NPH insulin.

Topics: Adult; Aged; Blood Glucose; Circadian Rhythm; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Administration Schedule; Female; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Placebos

Weight gain often occurs when insulin therapy is initiated. The long-acting insulin analog insulin detemir has been shown to be effective and well tolerated when used in basal-bolus regimens or as an add-on to oral antidiabetic drugs (OADs) and causes less weight gain than other insulins. The aim of this exploratory analysis was to investigate any correlations between weight change and occurrence of hypoglycemia with NPH insulin and insulin detemir.. The analysis was based on a 26-week, randomized, multicenter, open-label, parallel-group trial in which glycemic control, hypoglycemia, and weight change were compared between insulin detemir and NPH insulin. A total of 476 insulin-naive patients with type 2 diabetes treated with one or two OADs added insulin detemir (n=237) or NPH insulin (n=239) morning and evening to their current oral treatment. Weight gain data from this study were analyzed as a function of hypoglycemia frequency.. Both groups achieved excellent glycosylated hemoglobin control (insulin detemir, 6.6%; NPH insulin, 6.5% [difference not significant]). Weight gain with insulin detemir was less than half that of NPH insulin (1.2 vs. 2.8 kg, respectively [P<0.001]), and the overall risk of hypoglycemia was 47% lower with insulin detemir (P<0.001). No significant relationship between hypoglycemia and weight gain was seen with insulin detemir (P=0.2), while a statistically significant correlation was found for NPH insulin (P=0.003).. Hypoglycemia is predictive of weight gain with NPH insulin, but the same relationship is not seen with insulin detemir. It is therefore likely that the weight-sparing effect of insulin detemir involves other mechanisms.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Double-Blind Method; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Risk; Weight Loss

The IMPROVE study is a multinational, open-label, non-randomised, 26-week observational study assessing the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) treatment in type 2 diabetes in routine clinical practice. The principal aims of this report were to characterise the baseline population and physicians' treatment decisions.. Patients with type 2 diabetes who required insulin and whose physician had decided to initiate BIAsp 30 were eligible. At baseline, demographic data and detailed medical histories were collected and physicians recorded their reasons for starting BIAsp 30, the glycaemic targets set and the regimens chosen.. Data from 51,286 patients were included in analyses. Baseline glycaemic control was poor in all eight countries in the present analysis and in all prestudy treatment groups [no therapy, oral antidiabetic drugs (OADs) only, insulin with or without OADs], and the rates of vascular complications were high. Although the management of each of the three main measures of glycaemic control were key reasons for starting BIAsp 30, target-setting for postprandial glucose levels was variable. A twice-daily regimen was used to start BIAsp 30 therapy for 80% or more of patients.. The IMPROVE baseline data reaffirm the global nature of poor glycaemic control in type 2 diabetes and echo the concerns that initiation of therapy, particularly insulin, is commonly delayed in clinical practice. Although postprandial glucose control was a key driver for physicians' choice of BIAsp 30, this was not consistently reflected in the targets set.

Topics: Biphasic Insulins; Blood Glucose; Cohort Studies; Decision Making; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Treatment Outcome

To assess weight change when once-daily insulin detemir (detemir) or neutral protamine Hagedorn insulin (NPH) are used in already overweight Type 2 diabetes patients requiring intensified insulin therapy.. This 26-week randomized, controlled trial included adults with Type 2 diabetes [glycated haemoglobin (HbA(1c)) 7.5-11.0%, body mass index (BMI) 25-40 kg/m(2)] who had received two daily doses of insulin (at least one a premix) for > or = 3 months. Subjects received either detemir (n = 125) or NPH (n = 146) once daily in the evening and insulin aspart at main meals. Concomitant treatment with metformin was allowed. Basal insulin was titrated to a pre-breakfast plasma glucose target of 6.1 mmol/l without unacceptable hypoglycaemia. Insulin aspart was also titrated (target, postprandial glucose < or = 10.0 mmol/l without unacceptable hypoglycaemia).. At 26 weeks, weight had increased significantly less with detemir (0.4 kg) than with NPH (1.9 kg; difference 1.5 kg, P < 0.0001). BMI increase was also less with detemir than with NPH (difference 0.6 kg/m(2), P < 0.0001). HbA(1c) decreased from 8.9 to 7.8% (detemir) and from 8.8 to 7.8% (NPH; not significant for between-treatment difference). Incidence of hypoglycaemia was lower with detemir [relative risks 0.62 (all events) and 0.43 (nocturnal); P < 0.0001 for both].. PREDICTIVE BMI was the first study to examine the effect of once-daily detemir with weight as the primary endpoint in a large population of overweight Type 2 diabetes patients. Use of once-daily detemir for intensification of insulin therapy resulted in less weight gain, less hypoglycaemia and equivalent glycaemic control compared with NPH.

Topics: Administration, Oral; Aged; Body Mass Index; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Overweight; Weight Gain

Type 2 diabetes patients on premixed insulin are commonly prescribed biphasic insulin with low prandial insulin content, such as biphasic insulin aspart (BIAsp) 30, comprising 30% insulin aspart (IAsp). The new formulations BIAsp 50 and BIAsp 70 contain 50% and 70% soluble IAsp, respectively. We compared the pharmacodynamics (PD) and pharmacokinetics (PK) of BIAsp 30, 50, and 70 and IAsp in a glucose clamp trial.. In this randomized, double-blind, crossover study at a clinical research institute, 32 type 1 diabetes patients on basal-bolus therapy each underwent four glucose clamps (clamp level 5 mmol/L, duration 28 h post-dosing [12 h for IAsp]) and received a single dose of 0.4 U/kg BIAsp 30, 50, or 70 and IAsp. Main PD/PK outcome parameters measured were early- and late-phase glucose disposal (area under the curve of glucose infusion rate [AUC(GIR)]), nonesterified fatty acid concentrations, and IAsp concentrations.. With increasing proportions of soluble IAsp, the insulin formulations showed significantly higher early metabolic activity (ratio of AUC(GIR) 0-6 h: BIAsp 50/BIAsp 30 = 1.28 [P < 0.001], BIAsp 70/BIAsp 50 = 1.18 [P < 0.001), IAsp/BIAsp 70 = 1.15 [P < 0.01]) and lower late metabolic activity (ratio of AUC(GIR) 12-28 h: BIAsp 50/BIAsp 30 = 0.17 [P < 0.01], BIAsp 70/BIAsp 50 = 0.21 [P < 0.05]). Likewise, early IAsp levels were significantly greater and late PK concentrations were significantly lower with increasing proportion of soluble IAsp.. There are significant differences between the early and late PD and PK effects among BIAsp 30, 50, and 70 and IAsp that should allow tailored treatment with the convenience of prandial and basal insulin in each injection.

Topics: Adult; Area Under Curve; Biphasic Insulins; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Double-Blind Method; Fasting; Fatty Acids, Nonesterified; Female; Glucose Clamp Technique; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Young Adult

To study efficacy and safety of rosiglitazone + NPH insulin combined treatment in patients with type 2 diabetes mellitus (DM).. The trial included 43 patients with DM aged 44-75 on NPH insulin. The patients were divided into two groups. The study group received NPH insulin + a single morning dose of 4 mg/day rosiglitazone, the control group received NPH insulin only. The treatment lasted 24 weeks.. 24-week therapy in the study group lowered HbA(1c) from 8.16 +/- 0.23 to 6.82 +/- 0.18% (p<0.05), fasting glycemia--from 9.68 +/- 0.48 to 6.4 +/- 0.32 mmol/l, postprandial glycemia--from 12.3 +/- 0.44 to 8.4 +/- 0.56 mmol/l, HOMA-IR index--from 7.65 +/- 1.12 to 4.26 +/- 0.59. In group 2 HbAlc--from 7.84 +/- 0.15 to 7.49 +/- 0.17 (p<0.05), from 9.21 +/- 0.65 to 8.38 +/- 0.50 mmol/l, 11.92 +/- 0.53 to 9.97 +/- 0.45 mmol/l, 6.77 +/- 0.79 to 5.73 +/- 0.63. The combined treatment produced positive changes in lipid metabolism: total cholesterol decreased from 6.37 +/- 0.36 to 5.67 +/- 0.32 mmol/l (p<0.005), TG--from 2.46 +/- 0.64 mmol/l to 1.82 +/- 0.46 mmol/l (p<0.005), LDLP--from 3.99 +/- 0.40 to 3.58 +/- 0.37 mmol/l. Need in insulin diminished by 10%.. Treatment results showed that administration of rosiglitazone in combination with NPH insulin has a good safety and tolerance profile in type 2 DMp atients.

Topics: Adult; Aged; Blood Glucose; Carbohydrate Metabolism; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Humans; Hypoglycemic Agents; Insulin, Isophane; Lipids; Male; Middle Aged; Rosiglitazone; Thiazolidinediones; Treatment Outcome

To evaluate the efficacy and safety of the association of repaglinide, metformin and bedtime NPH insulin compared to two classic regimens: metformin plus NPH and two doses of NPH in patients with poorly controlled type 2 diabetes despite two or more oral antidiabetic drugs (OADs).. Random, parallel and open study of 24 weeks with 37 patients randomized into three therapeutic groups: group A (n=12) (repaglinide/metformin/NPH), group B (n=12) (metformin/NPH) and group C (n=13) (NPH/NPH). The insulin was adjusted in the visits to obtain a basal blood glucose <110 mg/dl. The endpoint criteria included HbA1c, blood glucose profile, hypoglycemias and body weight.. At the end of the study, group A presented HbA1c (mean+/-standard deviation) 7.2+/-0.7%, which was significantly less than B (8.8+/-0.1%) and C (8.4+/-1.2%). In terms of absolute reduction, there were only differences (p=0.01) between group A (-2.4+/-1.1%) and B (-0.7+/-1.2%). Group A presented lower postprandial blood glucose values (p<0.01). Nor were there any significant differences in weight gain and incidence of hypoglycemia.. The combination of repaglinide, metformin and bedtime NPH is safe and effective and it provides better postprandial blood glucose control. The association of metformin and a dose of NPH does not obtain suitable control in patients with a long evolution who have already received two or more OADs.

Topics: Aged; Blood Glucose; Blood Pressure; Body Mass Index; Carbamates; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Insulin, Isophane; Male; Metformin; Middle Aged; Piperidines; Prospective Studies; Safety; Weight Gain

To evaluate glycemic control using convenience-oriented biphasic insulin analog compared with intensified insulin therapy, we conducted a 6-month multicentric, open-label, randomized trial in Japanese insulin-naive patients with type 2 diabetes mellitus. A total of 160 adult patients at 19 centers were randomized into two groups: those who received twice-daily injections of biphasic insulin aspart 30 and those on three-times-daily injections of insulin aspart with or without NPH insulin (multiple daily injections). At 6 months, mean HbA(1c) decreased by approximately 2.5% in both groups. Reduction of HbA(1c) on both regimens was better in patients whose prior therapy before starting the study was only diet and exercise (-5.0%) than in patients who were previously taking oral antidiabetic agents (-1.0%). No incidence of major hypoglycemia was observed in either regimen. These results suggest that convenience-oriented insulin therapy using biphasic insulin analog is as useful as intensified insulin therapy with insulin analog for the treatment of type 2 diabetes mellitus over 6 months. Furthermore, early induction of insulin therapy in individuals hitherto using only diet and exercise may provide good glycemic control. This study suggests that convenience-oriented biphasic insulin aspart 30 might be a useful option for the treatment of type 2 diabetes mellitus, especially for insulin-naive patients over 6 months, although it should be changed to another regimen when expected efficacy is not obtained.

Topics: Aged; Analysis of Variance; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Japan; Male; Middle Aged; Patient Selection; Treatment Outcome

The safety and efficacy of biphasic insulin aspart (BIAsp30) were evaluated in patients uncontrolled on previous treatment (human insulin +/- oral hypoglycaemic agent [OHA] or OHA only) in routine clinical practice.. This was a large, multi-national, multicentre, prospective, 6-month study in type 2 diabetes mellitus patients who were prescribed BIAsp30. Changes in glycated haemoglobin (HbA(1c)), fasting plasma glucose (FPG), postprandial plasma glucose (PPPG), proportion who achieved target HbA(1c) < 7% and rate of hypoglycaemic episodes were assessed. This paper evaluates outcomes in patients by diabetes duration (< 5, 5-10, 10-20 or >/= 20 years) stratified by prior therapy.. After 6 months of treatment, glycaemia improved significantly across the duration subgroups. The improvement was better in insulin-naïve group versus prior insulin group: HbA(1c) decreased approximately 2.2%-points versus approximately 1.6%-points, FPG decreased approximately 4.5 mmol/L versus approximately 2.9 mmol/L and PPPG decreased approximately 6.8 mmol/L versus approximately 5.0 mmol/L. Target HbA(1c) was achieved by about one in four patients although insulin-naïve patients achieved this at comparatively lower BIAsp30 dose. Body weight remained relatively unchanged. Hypoglycaemic episodes appeared to be more frequent in the prior insulin group which decreased during the treatment period.. According to this observational study, in clinical practice, initiating or transferring uncontrolled patients to biphasic insulin aspart improved glycaemic control without using a strict insulin algorithm.

Topics: Aged; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Glycemic Index; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Postprandial Period; Prospective Studies; Treatment Failure

To assess the efficacy and safety of twice- and thrice-daily biphasic insulin aspart 30 (BIAsp 30) in Chinese subjects with type 2 diabetes inadequately controlled with oral antidiabetes drugs (OADs).. In this 24-week, multicenter, parallel-group, randomized, treat-to-target study, 321 Chinese insulin-naïve subjects with poorly controlled type 2 diabetes (fasting blood glucose >or=7.8 mmol/l and A1C >or=7.5%) were randomized (1:1) to twice- or thrice-daily (BID and TID groups, respectively) BIAsp 30 without OADs. Initial insulin doses were based on fasting blood glucose at randomization. Insulin dose was adjusted with algorithm-controlled titration to achieve premeal blood glucose of 4.4-6.1 mmol/l.. A1C decreased significantly in both groups (BID group -2.48 +/- 0.07%; TID group -2.81 +/- 0.07%). Thrice-daily BIAsp 30 showed superiority in A1C improvement (-0.33% [95% CI -0.53 to -0.13]; P < 0.01) and helped more subjects achieve A1C targets <7% (BID group 51.3% vs. TID group 65.8%; P < 0.01). Thrice-daily BIAsp 30 was more effective in subjects with baseline A1C >or=9% (<7%: BID group 41.5% vs. TID group 58.3%; P < 0.01). There was no significant difference in rates of overall and nocturnal major and minor hypoglycemia per subject year between groups. No significant differences in weight gain (BID group 3.87 +/- 0.28 kg; TID group 4.09 +/- 0.27 kg) and mean daily insulin doses (BID group 0.82 +/- 0.28 units/kg; TID group 0.86 +/- 0.34 units/kg) were observed.. Twice- and thrice-daily BIAsp 30 were effective in Chinese insulin-naïve subjects with poorly controlled type 2 diabetes. Thrice-daily BIAsp 30 offered greater reduction in A1C without increasing risk of hypoglycemia, insulin dose, and weight gain, especially in subjects with A1C >or=9%.

Topics: Administration, Oral; Adolescent; Adult; Biphasic Insulins; Blood Glucose; Blood Glucose Self-Monitoring; Body Mass Index; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Safety

The Physicians' Routine Evaluation of Safety and Efficacy of NovoMix 30 Therapy (PRESENT) study aims to assess the safety and efficacy of biphasic insulin aspart 30 (BIAsp 30) in patients with type 2 diabetes mellitus in routine clinical practice.. This was a 6-month, prospective, multinational, multiethnic observational study involving 21 977 patients from 13 countries (India, Iraq, Jordan, Kuwait, Lebanon, Qatar, Romania, Russia, Saudi Arabia, South Africa, South Korea, Turkey and the United Arab Emirates). The patients were transferred to BIAsp 30 with or without oral antidiabetic drugs (OADs) from prior treatment with OAD (n = 8583), insulin (n = 5942), OAD + insulin (n = 4673) or diet (i.e. treatment naive) (n = 1707). One thousand and seventy-two patients had incomplete or no information on previous treatment.. At 3 and 6 months, significant reductions from baseline were observed in the mean haemoglobin A(1c) (HbA(1c)) (-1.33 and -1.81%), fasting plasma glucose (-3.02 and -3.74 mmol/l) and postprandial plasma glucose (-4.76 and -5.82 mmol/l) (p < 0.001). A significantly greater proportion of patients achieved target HbA(1c) of less than 7% at 3 months (15.3%) and 6 months (27.7%) compared with baseline (4.8%) (p < 0.001). Overall, the mean HbA(1c) at 6 months was lowered in patients regardless of prior treatment: -2.15% (OAD), -1.45% (insulin), -1.47% (OAD + insulin) and -2.35% (treatment naive). In the overall cohort, the rate of total hypoglycaemia was reduced from 5.4 events per patient-year at baseline to 2.2 events per patient-year at study end (p < 0.001). Among prior treatment subgroups, the rates of total hypoglycaemia were reduced from 2.5 to 2.1 events per patient-year in the OAD group, from 9.6 to 2.2 events per patient-year in the insulin group and from 7.6 to 2.5 events per patient-year in the OAD + insulin group but were increased from 1.0 to 1.8 events per patient-year in the treatment-naive group (p < 0.001). There were 444 adverse drug reactions (ADRs), including 13 serious ADRs: lipodystrophy (three events), symptoms of generalized hypersensitivity (two events), acute painful neuropathy (one event), worsening of diabetic retinopathy (one event), oedema (one event) and unspecified ADRs (five events).. The use of BIAsp 30 monotherapy or in combination with OADs in clinical practice was effective and safe in patients with poorly controlled type 2 diabetes mellitus.

Topics: Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Family Practice; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Treatment Outcome

To investigate the relationship between changes in glycated haemoglobin (HbA(1c)) and postprandial glucose excursions on 1,5-anhydroglucitol (1,5-AG) in patients with Type 2 diabetes, utilizing the differential effects between biphasic insulin aspart 30 (BIAsp 30) or insulin glargine (IGlar) on postprandial glucose (PPG) levels.. 1,5-AG was measured using the GlycoMark assay at baseline and after 12 and 28 weeks in the INITiation of Insulin to reach HbA(1c) Target (INITIATE) study of 233 patients randomized to either BIAsp 30 or IGlar.. Baseline 1,5-AG was low and not significantly different (4.9 +/- 3.5 and 4.3 +/- 2.6 microg/ml in the BIAsp 30 and IGlar groups, respectively). After 28 weeks, the levels of 1,5-AG were higher in the BIAsp 30 than in the IGlar group (13.4 vs. 11.1 microg/ml, P = 0.008) and change from baseline was 25% greater with BIAsp 30 than IGlar (8.4 vs. 6.7 microg/ml, P = 0.011). 1,5-AG levels increased as a function of decreasing HbA(1c) or the average change in postprandial plasma glucose (PPG(ave)) with significant relationships for 1,5-AG/ HbA(1c) vs. HbA(1c) or 1,5-AG/PPG(ave )vs. PPG(ave) (both P < 0.0001), respectively.. As reported in previous publications, 1,5-AG reflects ambient glycaemic control and increases with reductions in HbA(1c) and postprandial glucose. The greater reductions in postprandial excursion achieved with BiAsp 30 compared with glargine were associated with greater increases in 1,5-AG. Even moderate elevations in HbA(1c) substantially lower 1,5-AG, suggesting that it can be most discriminating in identifying patients with excessive postprandial glucose excursions at HbA(1c) levels that approach the upper end of the normal range.

Topics: Adolescent; Adult; Aged; Biphasic Insulins; Diabetes Mellitus, Type 2; Epidemiologic Studies; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Postprandial Period

The aim of this analysis was to assess the efficacy and safety of intensifying insulin therapy from a basal-only regimen to biphasic insulin aspart 30 (BIAsp 30) in patients with type 2 diabetes previously failing to reach glycaemic targets.. The analysis is based on data from a subpopulation of the Physicians' Routine Evaluation of Safety and Efficacy of NovoMix 30 Therapy (PRESENT) study, which was a 6-month observational study in 15 countries. This subanalysis included patients previously receiving long-acting analogue insulin (AB; n = 348), or human basal insulin (long and intermediate acting) (HB; n = 3414), who were transferred to BIAsp 30. Efficacy end-points included change in glycated haemoglobin (HbA(1c)), fasting plasma glucose (FPG) and postprandial plasma glucose (PPG), from baseline to the end of the study. Episodes of hypoglycaemia, adverse events, and physician and patient satisfaction were also recorded. End-points were considered separately by previous basal regimen (AB or HB).. After 6 months' treatment with BIAsp 30, HbA(1c) was significantly lowered in both groups (-1.60% and -1.42% in the AB and HB groups; p < 0.0001 compared with baseline). Reductions in FPG and PPG were also statistically significant in both groups. The rate (events/patient/year) of overall hypoglycaemia remained relatively constant in patients switching from AB, but it was statistically lower in patients switching from HB (change from baseline -3.8; p < 0.001).. In routine clinical practice, patients with type 2 diabetes who are failing to reach glycaemic targets on basal insulin can achieve better glycaemic control without an increase in overall hypoglycaemia by intensifying with BIAsp 30.

Topics: Adult; Aged; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Prospective Studies; Treatment Failure; Treatment Outcome

Intensive insulin therapy composed of bolus and basal insulin has been believed as the most powerful recipe for glycemic control of both type 1 and type 2 diabetes. In this study, we investigated the effects of changes in basal/total daily insulin ratio (B/TD ratio) in type 2 diabetes patients on intensive insulin therapy including insulin glargine. The B/TD ratio used in our Japanese patients was about 0.35, and the ratio was increased up to about 0.46+/-0.12 without change of total insulin daily dose. After 24-week-treatment, mean glycated albumin of the patients whose B/TD ratio was increased was significantly lower than those of the patients whose B/TD ratio was not changed. Our results suggest that adequate supplementation of basal insulin may be important for maximum effect of bolus insulin even in Japanese who have serious defect in postprandial rapid insulin secretion.

Topics: Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Glycated Serum Albumin; Glycation End Products, Advanced; Glycosylation; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Serum Albumin

The aim of this study was to evaluate twice-daily injections of biphasic insulin lispro vs. basal-bolus (BB) therapy with regard to quality-of-life (QOL) and glycaemic control in insulin-naïve type 2 diabetic patients.. Twenty-eight patients with type 2 diabetes were randomized to receive either twice-daily 50/50 premixed insulin lispro (Mix50 group) or BB (NPH insulin at bedtime and preprandial insulin lispro) therapy (BB group) for 12 weeks. Glycated haemoglobin (HbA1C), 1,5-anhydroglucitol (1,5-AG), blood plasma glucose level, body mass index (BMI), daily total insulin dosage and insulin therapy-related QOL (ITR-QOL) were studied.. ITR-QOL was significantly better in the Mix50 than in the BB group (103.1 +/- 9.8 vs. 90.6 +/- 19.4; p < 0.05). HbA(1c) improved in both groups (from 11.1 +/- 2.1 to 6.9 +/- 1.0% with Mix50 vs. from 11.0 +/- 2.3 to 6.6 +/- 0.8% with BB therapy).. These results might suggest that twice-daily injections of premixed rapid-acting insulin analogue therapy could achieve good glycaemic control and better QOL compared with BB therapy in insulin-naïve type 2 diabetes.

Topics: Adult; Aged; Aged, 80 and over; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Male; Middle Aged; Quality of Life; Treatment Outcome; Young Adult

To evaluate the superiority of insulin glargine as basal insulin replacement by continuous glucose monitoring system (CGMS). Twenty-four patients with type 2 diabetes mellitus (T2DM) whose blood glucose was not well controlled with sulphanylureas were enrolled. At first, they were treated with extended-release glipizide (glucotrol XL) 5mg/d before breakfast for 2 weeks, then randomized to combination treatment with glargine (16 patients) or NPH (8 patients) and treated for 12 weeks. CGMS were carried in the second week after treatment with glucotrol XL, and in the 12th week after combination treatment. The data of CGMS showed: (1) When FPG were well controlled in both groups (glargine group versus NPH group: 6.0+/-1.0 mmol/L versus 5.8+/-1.3 mmol/L), the blood glucose level at 3:00 a.m. (5.1+/-0.9 mmol/L versus 4.2+/-0.8 mmol/L) were higher (P<0.05), TPG< or =3.0 mmol/L at night were lower (2.56+/-1.79 versus 5.88+/-1.96), and the rate of nocturnal hypoglycemia (1/16 versus 4/8) were less (P=0.028) in glargine group than those in NPH group. (2) CGMS showed that the daily blood glucose profile excursion were more smoother in glargine group than those in NPH group. In conclusion, it was confirmed with CGMS that compared with traditionally basal insulin replacement with NPH, the combination treatment with glargine injection at bedtime may be predominant for stabilizing the daily blood glucose profile excursion and decreasing the nocturnal hypoglycemia events incidence. So glargine may be a more ideal basal insulin replacement than NPH.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Evaluation Studies as Topic; Fasting; Female; Glipizide; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Monitoring, Physiologic; Treatment Outcome

This study investigated the effect of insulin glargine (LANTUS) versus NPH insulin on metabolic control and safety in Asian patients with Type 2 diabetes, inadequately controlled on oral hypoglycemic agents (OHAs).. In this open-label, randomized, parallel, multinational, 24-week, non-inferiority study, 443 patients received either once-daily insulin glargine (n=220) or NPH insulin (n=223) at bedtime, plus glimepiride (Amaryl).. Baseline characteristics were similar between the two groups. HbA(1c) levels decreased in the insulin glargine and NPH groups over the study period in the per-protocol (PP; -1.10% versus 0.92%) and full-analysis (FA; -0.99% versus -0.77%) populations. In the PP population, the difference between adjusted means (predefined equivalence region >-0.4%) was 0.19% (90% confidence interval [CI]: 0.02, 0.36), demonstrating non-inferiority between the two treatments. In a superiority analysis (FA population), the difference between adjusted mean changes in the two groups was 0.22% (95% CI: 0.02, 0.42), demonstrating the superiority of insulin glargine (p=0.0319). Moreover, the number of hypoglycemic episodes was significantly lower with insulin glargine versus NPH insulin (p<0.004), particularly severe (p<0.03) and nocturnal (p<0.001). Daily insulin dose increased from 9.6+/-1.5 to 32.1+/-17.6 U in the insulin glargine group and from 9.8+/-1.9 to 32.8+/-18.9 U in the NPH insulin group.. These results confirm earlier reports that insulin glargine provides superior glycemic control with less hypoglycemia and demonstrates that these benefits are consistent between different ethnicities.

Topics: Asian People; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Sulfonylurea Compounds; Treatment Outcome

To project the long-term clinical and economic outcomes of treatment with biphasic insulin aspart 30 (BIAsp 70/30, 30% soluble and 70% protaminated insulin aspart) vs. insulin glargine in insulin-naïve type 2 diabetes patients failing to achieve glycemic control with oral antidiabetic agents alone (OADs).. Baseline patient characteristics and treatment effect data from the recent 'INITIATE' clinical trial served as input to a peer-reviewed, validated Markov/Monte-Carlo simulation model. INITIATE demonstrated improvements in HbA1c favouring BIAsp 70/30 vs. glargine (-0.43%; p < 0.005) and greater efficacy in reaching glycaemic targets among patients poorly controlled on OAD therapy. Effects on life expectancy (LE), quality-adjusted life expectancy (QALE), cumulative incidence of diabetes-related complications and direct medical costs (2004 USD) were projected over 35 years. Clinical outcomes and costs were discounted at a rate of 3.0% per annum. Sensitivity analyses were performed.. Improvements in glycaemic control were projected to lead to gains in LE (0.19 +/- 0.24 years) and QALE (0.19 +/- 0.17 years) favouring BIAsp 70/30 vs. glargine. Treatment with BIAsp 70/30 was also associated with reductions in the cumulative incidences of diabetes-related complications, notably in renal and retinal conditions. The incremental cost-effectiveness ratio was $46 533 per quality-adjusted life year gained with BIAsp 70/30 vs. glargine (for patients with baseline HbA1c >/= 8.5%, it was $34 916). Total lifetime costs were compared to efficacy rates in both arms as a ratio, which revealed that the lifetime cost per patient treated successfully to target HbA1c levels of <7.0% and

Topics: Administration, Oral; Adult; Aged; Biphasic Insulins; Cost-Benefit Analysis; Diabetes Complications; Diabetes Mellitus, Type 2; Epidemiologic Methods; Female; Glycated Hemoglobin; Health Care Costs; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Treatment Failure; Treatment Outcome

Rapid-acting insulin analogs in basal-bolus regimens can reduce nocturnal hypoglycemia, so it is conceivable that twice-daily biphasic insulin analogs might reduce hypoglycemia in patients with insulin-treated type 2 diabetes. We used a continuous glucose monitoring system (CGMS) and self-reported episodes to investigate differences in the frequency of low glucose values in patients with type 2 diabetes, using either biphasic insulin aspart 30 (BIAsp 30) or biphasic human insulin 30 (BHI 30).. This was a double-blind, two-period, crossover trial involving 160 subjects. After 8 weeks' run-in, subjects were randomized to the first of two 16-week treatment periods.. No differences in overall incidence of low interstitial glucose (IG) were found. Twenty-four-hour plots of CGMS showed low IG was more frequent at night than during the day and was unrecognized by patients. At night, subjects spent significantly less time (percentage of total CGMS recorded) with IG <3.5 and <2.5 mmol/l during BIAsp 30 than during BHI 30 treatment, respectively (<3.5 mmol/l: 6.36 vs. 7.93% [mean], 0.67 vs. 2.43% [median], P = 0.018; <2.5 mmol/l: 2.35 vs. 2.86% [mean], 0 vs. 0% [median], P = 0.0467). No treatment difference in A1C was observed.. Overall rates of low glucose over 24 h were not different but were twice as frequent at night than during the day in individuals with type 2 diabetes. Compared with BHI 30, BIAsp 30 was associated with similar low IG readings over 24 h but with fewer nocturnal episodes and less self-reported nocturnal hypoglycemia.

Topics: Aged; Biphasic Insulins; Blood Glucose; Blood Glucose Self-Monitoring; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Monitoring, Ambulatory; Self Care

To compare combination use of repaglinide, metformin and bedtime Neutral Protamine Hagedorn (NPH) insulin with conventional approaches of insulin initiation in patients with Type 2 diabetes (T2DM).. Eighty-two patients with T2DM with suboptimal glycaemic control on oral glucose-lowering agents were randomized to one of three treatment regimens for 4 months. Group 1 received metformin and twice daily biphasic 30/70 human insulin mixture (n = 27), group 2 metformin and bedtime NPH insulin (n = 26) and group 3 metformin, bedtime NPH insulin and mealtime repaglinide (n = 25).. Seventy-five patients completed the study. Baseline and end-point mean HbA1c levels fell from 9.0 +/- 1.1 to 7.9 +/- 1.1% in group 1, 10.0 +/- 2.2 to 9.2 +/- 1.4% group 2 and 10.0 +/- 1.7 to 8.1 +/- 1.5% in group 3, respectively. All groups showed improvements in HbA1c. There was no significant difference between groups in the proportions of patients experiencing hypoglycaemia (29.6, 25.0 and 16.7%, respectively; P = 0.55) or in mean weight gain (2.9, 0.7 and 2.2 kg, respectively; P = 0.06). By 4 months, insulin doses were 0.63 +/- 0.32 IU/kg in group 1, 0.58 +/- 0.21 IU/kg in group 2 and 0.37 +/- 0.22 IU/kg in group 3 (group 3 vs. groups 1 and 2: P < 0.002).. The approach using repaglinide, metformin and NPH insulin improved glycaemic control with a similar safety profile to conventional insulin initiation in T2DM and produced final glycaemic control similar to metformin and a twice daily biphasic insulin mixture.

Topics: Adult; Aged; Aged, 80 and over; Carbamates; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin, Isophane; Male; Metformin; Middle Aged; Piperidines; Treatment Outcome; Weight Gain

Early worsening of diabetic retinopathy, characterized by cotton wool spots, intraretinal microvascular abnormalities and/or macular edema, can occur following improvement of glycemic control. In four randomized 28- to 52-week clinical trials comparing insulin glargine and NPH insulin in regard to glycemic control and frequency of hypoglycemia, ophthalmologic examinations and fundus photographs were included to assess frequency of early worsening of retinopathy or other early adverse ocular effects. Retinopathy progression rates at 28 weeks were 7-12% by clinical examination and 3-8% by photographic grading; corresponding rates of clinically significant macular edema (CSME) were 1-8% and 1-4%, respectively. Optic disc swelling was not observed clinically or in photographs. Two of the 24 possible comparisons (four trials, three outcomes, two assessment methods), both of which were photographic assessments in type 2 diabetes, were in/near the nominally significant range and favored NPH insulin: 28-week rates of >or=3-step retinopathy progression (insulin glargine: 16/213, 7.5%; NPH insulin: 6/220, 2.7%; p=0.028) and 52-week CSME rates (26/233, 11.2% and 14/214, 6.5%, respectively; p=0.098). Because the between-treatment differences were small and inconsistent across trials and assessment methods, and because overall rates were consistent with the natural course of diabetic retinopathy, we conclude that it is unlikely that insulin glargine carries a higher risk of early worsening or other early adverse effect than NPH insulin. These trials tended to exclude a large early adverse effect, such as optic disc swelling, but cannot assess longer-term effects; a 5-year randomized trial of insulin glargine versus NPH insulin has been initiated. Data from this manuscript have been presented as posters and published in abstract form at the European Association for the Study of Diabetes 2001 ( DIABETOLOGIA 44(Suppl 1):I-IV(A287), 2001) and the Latin American Diabetes Association 2001 (11-15 November 2001, Punta del Este, Uruguay; Poster 180) congresses.

Topics: Adult; Aged; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Female; Fluorescein Angiography; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged

This study examined the impact of insulin glargine introduction in basal-bolus therapy in type 1 and type 2 diabetic patients with inadequate metabolic control (A1c > 6.9%) using previous NPH insulin regime. In this uncontrolled, retrospective study, 49 patients (28F/21M), average age 24.7 +/- 16.5, mean duration of DM 13.2 +/- 10.1 yrs., 93.1% DM1 patients, received insulin glargine plus mealtime rapid-acting insulin (lispro or aspart) followed by 90-day treatment. We analyzed mean total insulin dose, incidence of hypoglycemic events, convulsive crisis, hyperglycemic complications and A1c levels before and after three months of introduction of glargine therapy. A1c values were determined using the HPLC instrument, with a normal range of 4.3% to 6.9%. After switching to insulin glargine therapy, mean A1c dropped from 10.2 +/- 2.0 to 9.1 +/- 1.8%, with significant impact (p= 0.019). We observed a significant reduction of 0.11 U/kg/day in total insulin dose, dropped from 0.75 U/kg of NPH to 0.64 U/kg of glargine, with significant correlation (p< 0.05). The introduction of glargine therapy was coincident with a decrease of hypoglycemic crisis (p= 0.02), convulsive events due to hypoglycemia (severe hypoglycemic crisis) (p= 0.023) and ketosis (p= 0.001) switching MDI-treated patients with improvement of metabolic control (reduction of A1c levels). This therapy improved quality of life in these patients due to a significant reduction of hypoglycemic (including severe) events, ketosis episodes and total daily insulin dose, with important impact on health public services.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Retrospective Studies; Treatment Outcome

To evaluate the efficacy and safety of adding biphasic insulin aspart 30 (BIAsp30; NovoMix 30) to existing oral antidiabetic agents (OADs) vs. optimizing OADs in a subgroup of Western Pacific patients with type 2 diabetes inadequately controlled on oral monotherapy or oral combination therapy.. This 26-week, multi-centre, open-labelled, randomized, two-arm parallel trial consisted of a 2-week screening period, followed by 24 weeks of treatment. Subjects randomized to BIAsp30 treatment (n = 129) received BIAsp30 once daily (o.d.) at dinnertime between Week 2 and Week 14, and those not reaching treatment targets were switched to twice daily (b.i.d.) BIAsp30 at Week 14 (n = 50). Subjects randomized to the OAD-only arm (n = 63) continued with their previous OAD treatment and, in an attempt to reach treatment goals, the dose was optimized (but OAD unchanged) in accordance to local treatment practice and labelling.. Significantly greater reductions in HbA(1c) over Weeks 0-13 with BIAsp30 (o.d.) vs. OAD-only treatment (1.16 vs. 0.58%; p < 0.001), and over Weeks 0-26, with BIAsp30 (o.d.) and BIAsp30 (b.i.d.) treatments vs. OAD-only treatment (1.24 vs. 1.34 vs. 0.67%; p < 0.01). Hypoglycaemic episodes were reported in 54% of the patients in BIAsp30 (o.d. and b.i.d. pooled) and 30% of the patients in OAD-only group. All episodes were minor or symptomatic, except for one in each treatment group, which was major.. Initiating BIAsp30 treatment is a safe and more effective way to improve glycaemic control in Western Pacific patients with type 2 diabetes inadequately controlled with oral monotherapy or oral combination therapy compared with optimizing oral combination therapy alone. In patients not reaching treatment target on BIAsp30 (o.d.), treatment with BIAsp30 (b.i.d.) should be considered.

Topics: Biphasic Insulins; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Treatment Outcome

To overcome the complicated mixing procedures required in the use of insulin formulations, premixed formulations consisting of rapid-acting and intermediate-type insulin in various mixing proportions have been developed. Biphasic insulin aspart 50 (BIAsp50) and 30 (BlAsp30) are 2 premixed formulations containing the active ingredient insulin aspart (IAsp) and consisting of a rapid-acting component soluble IAsp) and intermediate-acting component (protamine-crystallized protracted IAsp) in ratios of 50/50 and 30/70, respectively. These formulations are provided with the expectation that BIAsp30 and BIAsp50 will be beneficial for patients needing to improve their postprandial blood glucose control without changing their dietary habits and lifestyles. BIAsp30 has been widely used in medical practice, whereas BIAsp50 is being investigated in clinical trials.. The aim of this study was to compare the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of BIAsp50 (test) and BIAsp30 (reference) after single-dose SC injection in patients with type 2 diabetes mellitus.. This single-center, randomized, doubleblind, 2-period, crossover trial was conducted at the H.E.C. Science Clinic, Yokohama, Japan. Male and female patients aged > or = 20 years with a > or = 1 year history of type 2 diabetes were eligible. Patients were randomly assigned to 1 of 2 treatment sequences: group A received BIAsp30 in period 1 and BIAsp50 in period 2; group B received BIAsp50 in period 1 and BIAsp30 in period 2. All treatments were administered as an SC injection of a single dose (0.3 U/kg). The study periods were separated by a washout period of 4 to 21 days. For PK analysis of IAsp (maximum serum IAsp concentration [C(max,IAsp); primary end point], AUC of serum IAsp 0 to 120, 240, and 480 minutes after administration [AUC(0-120 min,IAspl), AUC(0-240 min,IAsp), and AUC(0-480 min,IAsp5) respectively], and time to (Cmax,IAsp) [T(max,IAsp)] ), blood samples were drawn immediately before (baseline) and at prespecified time points over 480 minutes after administration. The PD profiles of BIAsp50 and BIAsp30 were also examined by comparing the time course of the glucose infusion rate (GIR) using the euglycemic clamp technique. The PD end points were AUC of GIR 0 to 120 minutes after administration (AUC(0-120 min,GIR)), maximum GIR (GIR(max)), and time to GIRmax (T(max,GIR)). Tolerability was assessed using physical examination, including vital sign measurement, electrocardiography, body weight, adverse events (AEs), and clinical laboratory analysis (hematology and serum biochemistry).. Six men and 4 women were enrolled in the study (mean age, 62.4 years; mean body weight, 58.3 kg; mean body mass index, 22.22 kg/m(2); mean duration of diabetes, 9.53 years; and mean glycosylated hemoglobin concentration, 6.07%). Mean(Cmax,IAsp) with BIAsp50 was 63% higher than that for BIAsp30 (P < 0.002). The BIAsp50/BIAsp30 ratio with AUC(0-120 min,IAsp) was 1.68 (95% CI, 1.31-2.14). The BIAsp50/BIAsp30 ratiofor AUC(0-120 min,GIR) was 1.31 (95% CI, 1.02-1.68). A total of 9 AEs were reported in 5 patients, but none of the AEs were considered related to the study drug.. In this small PK/PD study in adults with type 2 diabetes in Japan, mean C(max,IAsp) was significantly higher with BIAsp50 than with BIAsp30, and AUC(0-120 min,IAsp) and AUC(0-120 min,GIR) were higher with BIAsp50 than with BIAsp30.

Topics: Area Under Curve; Biphasic Insulins; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glucose Clamp Technique; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Japan; Male; Middle Aged

To assess the effects of a structured in-patient diabetes training programme in people with Type 2 diabetes mellitus on a basal-bolus regimen using insulin glargine or NPH insulin and rapid-acting insulin analogues with respect to glycaemic control, weight development and incidence of hypoglycaemia in an outpatient-clinic setting.. This was a prospective, non-randomized, single centre, comparative observational study including 119 subjects. Pre-study treatment was a basal-bolus regimen with NPH insulin and a rapid-acting insulin analogue. Subjects either continued with NPH insulin (n=56) or were switched over to insulin glargine (n=63) at the discretion of the investigator (aiming at equal numbers in each group). Patients then attended routine out-patient follow up visits for 18 months.. HbA1c in the insulin glargine group improved statistically significant by -0.49%; [95%CI, -0.26, -0.71; p<0.001; HbA1c at endpoint 6.95+/-0.71%], whereas in the NPH group the reduction by -0.12% [95%CI, -0.31, 0.06; p=0.189; HbA1c at endpoint 7.22+/-0.74%] was statistically not significant. After 18 months of treatment the difference between treatment groups was 0.37% (p<0.015). Mean weight gain was significantly higher in the NPH group than in the glargine group (2.1 vs. 0.25 kg; p=0.025). A lower risk of hypoglycaemia in the glargine group (0.50 vs. 0.71 episodes/patient/month) did not reach statistical significance (p=0.081).. Following a structured in-patient diabetes training programme glycaemic control in people with Type 2 diabetes mellitus on a basal-bolus regimen improved significantly only with insulin glargine suggesting that training alone may not be sufficient to further improve metabolic control in relatively well controlled patients on NPH insulin. Therefore, in addition to a structured training programme also the insulin regimen should be optimized, e.g. by introduction of an insulin analogue.

Topics: Adult; Aged; Ambulatory Care Facilities; Body Weight; Diabetes Complications; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Patient Education as Topic; Prospective Studies

The efficacy of various regimens of initial insulin treatment in poorly controlled type 2 diabetes was compared with regard to diurnal glucose variation.. Randomized controlled trial. Setting. Insulin therapy initiated on hospital wards, follow-up as outpatients for 12 months.. Fifty-two type 2 diabetic patients (HbA1c >7.5%, mean 9.8%) on maximal oral therapy. Interventions. Insulin only (IO), bedtime insulin with sulphonylurea (glipizide) (IS), or bedtime insulin with metformin (IM).. HbA1c and body weight.. HbA1c decreased on average by 1.8, 1.0 and 1.5 percentage points in the IO, IS, and IM groups, respectively (p always <0.025). Body weight increased, most in the IO patients (+6.2 kg), least in the IM patients (+3.4 kg). Analysing all treatment groups combined, a similar HbA1c reduction was observed in patients with overall hyperglycaemia (low fasting plasma glucose/HbA1c ratio) and in patients with fasting hyperglycaemia (high fasting plasma glucose/HbA1c ratio). Within the overall hyperglycaemia group, the IS and IM patients had smaller decreases in HbA1c (-1.5 and -1.3 percentage points, respectively) than the IO patients (-2.7 percentage points). On the other hand, within the fasting hyperglycaemia group HbA1c reductions were -1.2, -0.8 and -1.5 percentage points, in the IO, IS, and IM groups, respectively.. Not all poorly controlled type 2 diabetic patients should automatically be treated with an oral agent and bedtime insulin. Two daily insulin injections is a valid choice, particularly if the patient has overall hyperglycaemia.

Topics: Administration, Oral; Adult; Blood Glucose; Circadian Rhythm; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Fasting; Follow-Up Studies; Glipizide; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin, Isophane; Insulin, Long-Acting; Metformin; Middle Aged

The results of using status measures to identify any changes in treatment satisfaction strongly suggest a need for specific change instruments designed to overcome the ceiling effects frequently observed at baseline. Status measures may leave little room to show improvement in situations where baseline ceiling effects are observed. A change version of the DTSQ (DTSQc) is compared here with the original status (now called DTSQs) version to test the instruments' comparative ability to demonstrate change.. Two multinational, openlabel, randomised-controlled trials (one for patients with type 1 diabetes, the other for type 2) compared new, longer-acting insulin glargine with standard NPH basal insulin. The DTSQs was completed at baseline and the DTSQs and DTSQc at final visit by 351 English- and German-speaking patients. DTSQc scores were compared with change from baseline for the DTSQs, using 3-way analysis of variance, to examine Questionnaire, Treatment and Ceiling effects (i.e. baseline scores at/near ceiling).. Significant Questionnaire effects and a Questionnaire x Ceiling interaction (p < 0.001) in both trial datasets showed that the DTSQc detected more improvement in Treatment Satisfaction than the DTSQs, especially when patients had DTSQs scores at/near ceiling at baseline. Additionally, significant Treatment effects favouring insulin glargine (p < 0.001) and a Treatment x Questionnaire interaction (p < 0.019), with the DTSQc showing more benefits, were found in the type 1 trial. Results for Perceived Hyper- and Hypoglycaemia also demonstrated important differences between the questionnaires in the detection of treatment effects. Tests of effect sizes showed these differences in response to change to be significantly in favour of the DTSQc.. The DTSQc, used in conjunction with the DTSQs, overcomes the problem of ceiling effects encountered when only the status measure is used and provides a means for new treatments to show greater value than is possible with the DTSQs alone.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Endpoint Determination; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Outcome Assessment, Health Care; Patient Satisfaction; Psychometrics; Surveys and Questionnaires; Time Factors

The primary objective of this study was to investigate the difference in the proportion of patients with conventionally detected hypoglycemia compared with continuous glucose monitoring system (CGMS, Medtronic MiniMed, Sylmar, CA)-detected glucose values < or = 60 mg/dL (< or = 3.3 mmol/L), during the 72-h CGMS measurement period after 8 weeks' treatment with insulin glargine.. This was a multicenter (n = 125), open-label, single-arm study in patients with Type 2 diabetes mellitus (T2DM) on multiple daily injections. Patients received NPH insulin (2-week run-in) followed by glargine (8-week treatment phase). Glucose levels were measured by CGMS and self-monitored blood glucose (SMBG) profiles over the 72-h pre- and post-treatment phase.. The full analysis set contained 367 patients [male 59%; mean age 59.2 years; mean body mass index 31.7 kg/m(2); mean hemoglobin A1c (HbA1c) 6.9%]. At end point, 209 patients (56.9%) experienced hypoglycemia according to CGMS; 97 (26.4%) recorded hypoglycemia by conventional methods. CGMS- and SMBG-determined mean daytime glucose levels were similar at baseline and end point; however, nocturnal glucose levels were significantly lower with CGMS versus SMBG at baseline [130.2 vs. 145.0 mg/dL (7.2 vs. 8.1 mmol/L)] and at end point [123.3 vs. 137.3 mg/dL (6.8 vs. 7.6 mmol/L)]. Glucose levels measured by CGMS and SMBG decreased, and HbA1c levels decreased from 6.90% at screening to 6.67% at end point (P < 0.001).. This study demonstrates that CGMS can be successfully employed in large clinical trial settings in patients with T2DM. This easy-to-implement method may provide additional insights into glucose levels and valuable information regarding the time patients spend within the preferred glucose range.

Topics: Aged; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Time Factors

Modern premixed insulins offer a flexible approach to the initiation of insulin therapy in patients with poorly controlled type 2 diabetes. A disadvantage of twice-daily regimens of biphasic insulin aspart 30 (BIAsp 30) is that lunchtime control (when no insulin is administered) can be suboptimal. Therefore, it is possible that administering BIAsp 30 thrice daily might further optimize glycemic control and offer an option for patients in whom metformin (MET) is contraindicated.. This study evaluated the efficacy and safety profiles of 2 different regimens of BIAsp 30 compared with a regimen consisting of oral antidiabetic drugs (OADs) alone.. In this multicenter, randomized, open-label, parallel-group trial, insulin-naive patients with poorly controlled type 2 diabetes (baseline glycosylated hemoglobin [HbA(1c) > or =8.0%) who were taking OADs (a sulfonylurea or meglitinide with/without MET or MET only) were randomized to receive BIAsp 30 TID, BIAsp 30 BID + MET, or continuation of their current OAD therapy for 16 weeks. The primary end point was HbA(1c) at the end of the study. Secondary end points included reductions in HbA(1c), mean blood glucose (BG), prandial increment, mean 7-point self-monitored BG profile, weight changes, tolerability (hypoglycemia, adverse events), and satisfaction/quality of life (derived from 2 questionnaires completed at weeks 0, 8, and 16).. The study enrolled 308 insulin-naive patients with type 2 diabetes (78.9% female; mean age, 58.3 years; body mass index, 29.4 kg/m(2); HbA(1c), 10.3%). Both BIAsp 30 TID and BIAsp 30 BID + MET were associated with significantly greater mean (SD) reductions in HbA(1c) relative to OADs alone (absolute percent reduction: 2.9% [1.5%], 3.0% [1.6%], and 2.1% [1.4%], respectively; P < 0.001, both insulin groups vs OAD group) and improved post-prandial glucose control (reduction in mean post-prandial glucose:-6.32 [4.07], -6.44 [4.70], and -3.59 [4.22] mmol/L; P < 0.001, both insulin groups vs OAD group). The mean decrease in the prandial increment was -1.26 mmol/L for BIAsp 30 TID, -2.15 mmol/L for BIAsp 30 BID + MET, and -0.44 mmol/L for OAD. The differences in reduction in the prandial increment were statistically significant for BIAsp 30 TID versus OAD (P = 0.047), BIAsp 30 BID + MET versus OAD (P < 0.001), and BIAsp 30 TID versus BIAsp 30 BID + MET (P = 0.042). Mean body weight increased significantly from baseline with both BIAsp 30 TID and BIAsp 30 BID + MET (+1.71 and +1.50 kg, respectively; both, P < 0.001), and decreased significantly in the OAD group (-0.75 kg; P = 0.003). There were no major hypoglycemic events, and most hypoglycemic events were recorded as symptoms only (144/158 [91.1%]). There were no significant differences in the mean frequency of overall hypoglycemic episodes between BIAsp 30 TID and BIAsp 30 BID + MET (0.73 and 0.69 episodes per patient-year, respectively).. In these patients with type 2 diabetes that was poorly controlled by OADs, BIAsp 30 TID and BIAsp 30 BID plus MET were associated with significantly greater reductions in HbA(1c) and postprandial BG compared with OADs alone. The insulin regimens were associated with significantly more weight gain than OADs alone. There were no differences in rates of hypoglycemia between the insulin regimens.

Topics: Biomarkers; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Endpoint Determination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Metformin; Middle Aged; Quality of Life; Russia; Weight Gain

To compare characteristics of better responders to new regimen therapy with non-responders.. In a 12-week, two-center, open, parallel group clinical trial, 80 type 2 diabetic patients treated with twice-daily premixed 30 R insulin with or without OAD (s) [fasting blood glucose (FBG) 7.8 - 16.7 mmol/L, HbA1c 7% - 10%] were randomized to once-daily morning insulin glargine plus glimepiride 3 mg or premixed 30 R insulin (70/30) twice-daily plus glimepiride 3 mg. Insulin dosage was titrated to target FBG 8.0% vs 8.9%-->7.8%, P > 0.05). However, hypoglycemic episodes were significantly higher in premixed-insulin-treated subjects than in glargine-treated subjects [total: 123 vs 57; proved hypoglycemic episodes 94 (76%) vs 21 (47%), chi(2) = 23.692, P < 0.01], The frequency of hypoglycemia before lunch was especially greater in premixed-insulin-treated subjects 64 (52%) vs 17 (30%), chi(2) = 7.762, P = 0.005. Several subjects from the premixed arm experienced too frequent hypoglycemic episodes to be recorded during 10AM-11AM almost every day. Subgroup analysis for patients treated with glargine: 28.2% (11 cases) of the patients in this group attained HbA1c 8.5% at 12 weeks, mean daily dosage for glargine were (0.66 +/- 0.30) U.kg(-1).d(-1). There were significant differences of baseline HbA1c, diabetes duration and baseline postprandial C-peptide between the two subgroups in glargine arm (HbA1c: 8.1% +/- 0.8% vs 9.6% +/- 1.2%; duration: 10 (6 - 14.5) years vs 13 (8 - 19.5) years; postprandial c peptide: 2.5 nmol/L (1.4 - 3.3) vs 1.4 (1.2 - 2.6) nmol/L, all P < 0.05).. Type 2 diabetic patients treated with twice-daily injection of premixed 30 R insulin with or without OAD (s) can be effectively and safely switched to basal insulin plus OAD. Pretreatment HbA1c, diabetes duration and postprandial C peptide are the key factors that closely related to efficacy of this new regimen.

Topics: Administration, Oral; Adult; Aged; Diabetes Mellitus, Type 2; Drug Administration Routes; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome

This study compared glycaemic control achieved with biphasic insulin aspart 30 (BIAsp 30) monotherapy, BIAsp 30 plus metformin and glibenclamide plus metformin in patients with type 2 diabetes not adequately controlled with metformin.. In this multinational, open-labelled, parallel group, 16-week trial, 341 patients (patients not adequately controlled with metformin for at least 1 month) with type 2 diabetes were studied. Patients were randomized to receive BIAsp 30, twice daily (n = 107 exposed to treatment), or BIAsp 30, twice daily, plus metformin (n = 108) or glibenclamide plus metformin (n = 114). The primary endpoint was HbA(1c) at end of trial; adverse events, hypoglycaemia episodes, blood lipids and weight were also monitored.. In the total population (HbA(1c) 7.5-13.0% at screening), end-of-trial HbA(1c) levels were lower in patients receiving BIAsp 30 plus metformin compared with those receiving BIAsp 30 only [mean treatment difference (+/-s.e.m), 0.39 +/- 0.15%, p = 0.007]. In a subpopulation (HbA(1c) > or = 9.0% at baseline, n = 193), patients receiving BIAsp 30 plus metformin had significantly lower HbA(1c) levels at the end of the trial compared with those receiving glibenclamide plus metformin (treatment difference, 0.46 +/- 0.21%, p = 0.027). Mean body weight (+/-s.d) at the end of the trial was significantly lower in patients receiving glibenclamide plus metformin compared with those receiving BIAsp 30 only (84.3 +/- 13.3 kg vs. 88.9 +/- 16.9 kg, p < 0.001). No major hypoglycaemic episodes were recorded during the trial, and incidence rates for minor and symptoms-only hypoglycaemia were low and similar between treatment groups (0.03-0.04 events/patient/week).. BIAsp 30 added to metformin could be an appropriate therapeutic option for achieving good glycaemic control, compared with the addition of a second oral agent, particularly where HbA(1c) > or = 9%.

Topics: Biphasic Insulins; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Glyburide; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Metformin; Middle Aged; Treatment Outcome

In type 2 diabetic patients we compared 9 months of combination therapy with insulin glargine and metformin with 9 months of NPH insulin combined with metformin. The primary focus was changes in HbA(1c); secondary focus was diurnal glucose profiles and symptomatic hypoglycaemia.. In this investigator-initiated open, parallel-group clinical trial involving seven centres, 110 insulin-naive type 2 diabetic patients with poor glycaemic control (HbA(1c) >or=8.0%) on oral hypoglycaemic agents (90% using sulfonylurea plus metformin) were randomised to receive bedtime insulin glargine with metformin (G+MET) or bedtime NPH with metformin (NPH+MET) for 36 weeks. The patients were taught how to self-adjust their insulin dose and use a modem to send the results of home glucose monitoring to treatment centres. The goal was to achieve a fasting plasma glucose (FPG) of 4.0 to 5.5 mmol/l in both groups.. During the last 12 weeks, FPGs averaged 5.75+/-0.02 and 5.96+/-0.03 mmol/l (p<0.001) and insulin doses were 68+/-5 and 70+/-6 IU/day (0.69+/-0.05 and 0.66+/-0.04 IU kg(-1) day(-1), NS) in the G+MET and NPH+MET groups, respectively. At 36 weeks, mean HbA(1c) was 7.14+/-0.12 and 7.16+/-0.14%, respectively (NS). Symptomatic, but not confirmed symptomatic, hypoglycaemia was significantly lower during the first 12 weeks in the G+MET group (4.1+/-0.8 episodes/patient-year) than in the NPH+MET group (9.0+/-2.3 episodes/patient-year, p<0.05), but not significantly different thereafter. Glucose levels before dinner were higher in the NPH+MET group (10.1+/-0.3 mmol/l) than in the G+MET group (8.6+/-0.3 mmol/l, p=0.002) throughout the 36-week study. With regard to baseline characteristics such as initial glycaemia or C-peptide, there was no difference between patients who achieved good glycaemic control (HbA(1c) <7.0%) and those who did not. Differences were seen in the following: between study centres, weight gain during the run-in period and insulin therapy, and FPG during the last 12 weeks (5.7+/-0.2 vs 6.7+/-0.3 mmol/l for patients reaching vs those not reaching target, p<0.01).. Good glycaemic control can be achieved with both G+MET and NPH+MET. Use of G+MET reduces symptomatic hypoglycaemia during the first 12 weeks and dinner time hyperglycaemia compared with NPH+MET.

Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Lipid Metabolism; Liver; Male; Metformin; Middle Aged

In normal subjects, approximately half of the daily insulin requirement constitutes basal insulin. We investigated whether increasing the dose of insulin glargine up to half of the total insulin requirement could lead to better glycemic control in type 2 diabetic patients who were treated on basal-prandial insulin therapy. A total of 62 patients with type 2 diabetes on mealtime rapid-acting insulin analogue and bedtime NPH were randomized to either continuation of bedtime NPH (n=31) or morning glargine (n=31) for 6 months while continuing the aspart/lispro at each meal. The two groups were matched for age, sex, diabetes duration, BMI, HbA(1C), endogenous insulin secretion, and proportion of numbers using aspart/lispro and using oral hypoglycemic agents. The dose of insulin glargine was increased by 2-4 units to meet the target fasting blood glucose, whereas the dose of NPH was principally unchanged as a control group. Mean HbA(1C) at baseline was similar between patients with glargine and NPH (7.2% versus 6.9%). The percentage of glargine dose increased significantly (31% at baseline to 48% at 6 months) without any significant changes in total insulin dose. Mean HbA(1C) at 3 months was 6.6% with glargine and 7.0% with NPH (P<0.0001, adjusted mean change between-treatment difference 0.6% [95% CI 0.3-0.9]), and the values at 6 months were 6.6% and 6.9%, respectively (P=0.007). Frequency of hypoglycemia did not differ between the groups. Increasing the dose of glargine without changing the total daily insulin dose resulted in significantly better glycemic control in type 2 diabetic patients on basal-prandial insulin therapy. Conversion from bedtime NPH to morning glargine appears efficacious with no increase in frequency of hypoglycemia.

Topics: Adult; Aged; Blood Glucose; Circadian Rhythm; Diabetes Mellitus, Type 2; Drug Administration Schedule; Eating; Female; Humans; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged

The pharmacokinetic and pharmacodynamic properties of biphasic insulin aspart (BIAsp 30) (30% soluble, 70% protaminated insulin aspart [IAsp]) and insulin glargine (IGlarg) were compared.. Twelve people with type 2 diabetes took part in two 24-h isoglycaemic clamp studies, 1 week apart. Patients were randomised to treatment with 0.5 U/kg of BIAsp 30 (0.25 U/kg at 08.30 h and 0.25 U/kg at 20.30 h) or 0.50 U/kg IGlarg at 08.30 h. Both insulins were given by subcutaneous injection into the anterior abdominal wall. The plasma glucose, glucose infusion rates, plasma insulin and C-peptide concentrations were measured.. All 12 patients were men; mean (+/-SD) age was 58.8 (8.9) years, BMI 31.0 (3.0) kg/m2 and HbA(1c) 7.1 (0.6)%. Plasma glucose was constant throughout the 24-h clamp period. After each injection of BIAsp 30, glucose infusion rates increased, reaching a distinct peak approximately 3-5 h after injection. A much flatter postinjection profile was observed following IGlarg administration. Plasma insulin concentrations rose rapidly after each injection of BIAsp 30, reaching a distinct peak after approximately 2-3 h. A flatter plasma insulin profile reached a plateau approximately 6-16 h after IGlarg administration. Plasma C-peptide fell below baseline after both injections of BIAsp 30 but remained unaltered after IGlarg injection.. The pharmacodynamic and pharmacokinetic profiles were 34 and 28%, respectively, higher following equivalent doses (0.5 U/kg) of BIAsp 30 given as two split doses than following IGlarg given as a single daily dose.

Topics: Aged; Area Under Curve; Biphasic Insulins; Blood Glucose; C-Peptide; Cross-Over Studies; Diabetes Mellitus, Type 2; Glucose Clamp Technique; Humans; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Kinetics; Male; Middle Aged

Type 2 diabetes (T2DM) patients often fail to achieve adequate glycemic control with oral antidiabetic drugs (OADs). Insulin has been shown to improve glycemic control in these patients but with increased risk of hypoglycemia. This study compared the efficacy and safety of insulin glargine and NPH insulin, both in combination with a once-daily fixed dose of glimepiride, in terms of glycemic control and incidence of hypoglycemia.. In this open-label, 24-week randomized trial in ten Latin American countries, T2DM patients poorly controlled on OADs (HbA1c > or = 7.5 and < or = 10.5%) received glimepiride plus insulin glargine (n = 231) or NPH insulin (n = 250) using a forced titration algorithm. The primary endpoint was the equivalence of 24-week mean changes in HbA1c.. Insulin glargine and NPH insulin achieved similar HbA1c reductions (adjusted mean difference -0.047; 90% CI -0.232, 0.138; per-protocol analysis). Confirmed nocturnal hypoglycemia was significantly lower with insulin glargine vs. NPH insulin (16.9 vs. 30.0%; p <0.01; safety analysis). Patients receiving insulin glargine were significantly more likely to achieve HbA1c levels < 7.0% without hypoglycemia (27 vs. 17%; p = 0.014; per-protocol analysis). There was a more pronounced treatment satisfaction improvement with insulin glargine vs. NPH insulin (p <0.02; full analysis). The proportion of patients who lost time from work or normal activities due to diabetes was lower with insulin glargine vs. NPH (1.8 vs. 3.3%; full analysis).. In patients with T2DM, inadequately controlled on OADs, once-daily insulin glargine plus glimepiride is effective in improving metabolic control with a reduced incidence of nocturnal hypoglycemia compared with NPH insulin.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Sulfonylurea Compounds

To assess efficacy and tolerability of insulin detemir or NPH insulin added to oral therapy for type 2 diabetes in a treat-to-target titration protocol.. Individuals (n = 476) with HbA(1c) (A1C) 7.5-10.0% were randomized to addition of twice-daily insulin detemir or NPH insulin in a parallel-group, multicenter trial. Over 24 weeks, insulin doses were titrated toward prebreakfast and predinner plasma glucose targets of < or =6.0 mmol/l (< or =108 mg/dl). Outcomes assessed included A1C, percentage achieving A1C < or =7.0%, risk of hypoglycemia, and body weight.. At 24 weeks, A1C had decreased by 1.8 and 1.9% (from 8.6 to 6.8 and from 8.5 to 6.6%) for detemir and NPH, respectively (NS). In both groups, 70% of participants achieved an A1C

Topics: Administration, Oral; Adult; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Weight Gain

To evaluate the time-action profiles and the dose-response relationship of the long-acting insulin analogues insulin detemir (IDet) and NPH insulin (NPH) in type 2 diabetic patients belonging to different ethnic groups.. Forty-eight type 2 diabetic patients belonging to different ethnic groups (three groups of 16 African Americans (AA), 16 Hispanics/Latinos (HL) and 16 Caucasians) participated in this double-blind crossover trial. Each patient took part in six 16-h isoglycaemic glucose clamps (clamp target 7.2 mmol/l) and was randomly allocated to three doses (0.3, 0.6 and 1.2 (I)U/kg) of IDet and NPH, respectively.. IDet and NPH showed comparable pharmacodynamic effects [the area under the glucose infusion rate curve (AUC(GIR 0-16 h)) (mg/kg)] in the investigated dose range: IDet, 0.3 U/kg, 207 AA, 535 HL, 285 Caucasians; 0.6 U/kg, 1203 AA, 824 HL and 1126 Caucasians; 1.2 U/kg, 1502 AA, 1977 HL and 2269 Caucasians; NPH, 0.3 IU/kg, 733 AA, 1148 HL and 1148 Caucasians; 0.6 IU/kg, 1395 AA, 1976 HL and 1077 Caucasians; 1.2 IU/kg, 2452 AA, 3296 HL and 2455 Caucasians. Both IDet and NPH showed a linear dose-response relationship in all three groups (p = 0.31), without any significant differences in slope (p = 0.71) or intercept (p = 0.51). Comparable results were obtained for pharmacokinetics.. These results confirm a linear dose-response relationship of IDet, without any relevant differences between ethnic groups. This suggests that similar dosing recommendation can be used for IDet in type 2 diabetic patients belonging to different ethnic group.

Topics: Adult; Black or African American; Body Mass Index; Cross-Over Studies; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Double-Blind Method; Female; Glucose Clamp Technique; Hispanic or Latino; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; White People

To show that a thrice daily meal-time biphasic insulin aspart (BIAsp) treatment regimen is as efficacious as a 4 times daily basal-bolus regimen with human isophane insulin (NPH) and insulin aspart (IAsp).. A multinational, randomised, open-label parallel-group trial in 394 patients with type 2 diabetes on a once or twice daily insulin regimen. Patients were randomised 1:1 to BIAsp or IAsp+NPH for 16 weeks. The BIAsp group was treated according to individual needs using BMI as a surrogate index of insulin resistance. Subjects administered BIAsp 70 (BMI< or =30 kg/m (2)) or BIAsp 50 (BMI>30 kg/m (2)) with breakfast and lunch and BIAsp 30 with dinner. The IAsp+NPH group injected IAsp at meals and NPH at bedtime as basal insulin. HbAlc levels after 16 weeks were compared between treatments using a predefined non-inferiority criterion of 0.4%. The incidence of hypoglycaemic episodes and adverse events was evaluated.. Mean HbAlc (+/-SD) decreased from 9.1+/-0.7% to 7.8+/-1.0% with both treatments. Glycaemic control provided by BIAsp was non-inferior to that obtained by the IAsp+NPH (intention to treat ITT) population: diff, HbAlc -0.05%; 95% CI (-0.24; 0.14); per protocol (PP) population: diff, HbAlc -0.03%; 95% CI (-0.23; 0.16). Similar improvements in glycaemic control in both groups were confirmed by self-measured 8-point plasma glucose (PG) profiles, average and fasting PG concentrations, and average prandial PG increments. The incidence of adverse events and hypoglycaemic episodes was similar in the two treatment groups.. A thrice daily meal-time BIAsp regimen is a suitable alternative to an intensified insulin regimen in people with inadequately controlled type 2 diabetes mellitus, and requires fewer daily injections than a basal-bolus therapy without compromising efficacy and safety.

Topics: Aged; Biphasic Insulins; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Routes; Drug Administration Schedule; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Injections; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Treatment Outcome

To compare the efficacy and safety of two analog insulins as starting regimens in insulin-naïve Type 2 diabetes patients.. In this randomized, open-label parallel study, twice-daily biphasic insulin aspart 30 (30% soluble and 70% protaminated insulin aspart; BIAsp 30) plus metformin (met) was compared with once-daily insulin glargine (glarg) plus glimepiride (glim) in 255 insulin-naïve patients (131 male; mean+/-SD age, 61.2+/-9.1 years). Mean baseline HbA (1c) (+/-SD) was 9.2+/-1.4% and 8.9+/-1.3% for BIAsp 30 plus met ( N=128) and glarg plus glim ( N=127), respectively ( P=0.0747). Primary endpoint was the difference in absolute change in HbA (1c) between groups after 26 weeks of treatment.. HbA (1c) change was significantly greater in the BIAsp 30 plus met group than the glarg plus glim group (between-group difference: -0.5% (95% CI: -0.8; -0.2); P=0.0002). Mean prandial plasma glucose increment was significantly lower for BIAsp 30 plus met compared with glarg plus glim: 1.4+/-1.4 mmol/l vs. 2.2+/-1.8 mmol/l; P=0.0002. During the maintenance phase (weeks 6-26), one major hypoglycemic episode occurred in each group; 20.3% and 9% of patients experienced minor hypoglycemic episodes in the BIAsp 30 plus met and glarg plus glim groups, respectively ( P=0.0124). At end-of-trial, mean daily insulin doses were 0.40 U/kg BIAsp 30 and 0.39 U/kg glarg. Glarg plus glim-treated patients experienced significant weight gain of 1.5 kg (95% CI: 0.84; 2.19; P<0.0001). Weight change with BIAsp 30 plus met of +0.7 kg was not statistically significant (95% CI: -0.07; 1.42; P=0.0762).. Starting insulin in Type 2 diabetes patients with twice-daily BIAsp 30 plus met can reduce HbA (1c) and mean prandial plasma glucose increment to a greater extent than once-daily glarg plus glim.

Topics: Aged; Biphasic Insulins; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Metformin; Middle Aged; Sulfonylurea Compounds; Treatment Outcome

The aim of this study was to compare the efficacy and safety of a basal-bolus insulin regimen comprising either insulin detemir or neural protamine hagedorn (NPH) insulin in combination with mealtime insulin aspart in patients with type 2 diabetes.. This was a 26-week, multinational, open-label, parallel group trial with 505 patients with type 2 diabetes (mean age, 60.4 +/- 8.6 years; mean BMI, 30.4 +/- 5.3 kg/m(2); mean HbA(1c), 7.9 +/- 1.3%). Patients, randomized 2:1 to insulin detemir or NPH insulin, received basal insulin either once or twice daily according to their pretrial insulin treatment and insulin aspart at mealtimes.. After 26 weeks of treatment, significant reductions in HbA(1c) were observed for insulin detemir (0.2%-points, p = 0.004) and NPH insulin (0.4%-points; p = 0.0001); HbA(1c) levels were comparable at study end (insulin detemir, 7.6%; NPH insulin, 7.5%). The number of basal insulin injections administered per day had no effect on HbA(1c) levels (p = 0.50). Nine-point self-measured blood glucose (SMBG) profiles were similar for the two treatment groups (p = 0.58), as were reductions in fasting plasma glucose (FPG) (insulin detemir, 0.5 mmol/l; NPH insulin, 0.6 mmol/l). At study end, FPG concentrations were similar for the two treatment groups (p = 0.66). By contrast, within-subject day-to-day variation in fasting SMBG was significantly lower with insulin detemir (p = 0.021). Moreover, patients receiving insulin detemir gained significantly less body weight than those who were administered NPH insulin (1.0 and 1.8 kg, respectively, p = 0.017). The frequency of adverse events and the risk of hypoglycaemia were comparable for the two treatment groups.. Patients with type 2 diabetes, treated for 26 weeks with insulin detemir plus insulin aspart at mealtimes, experienced comparable glycaemic control but significantly lower within-subject variability and less weight gain compared to patients treated with NPH insulin and insulin aspart. Insulin detemir was well tolerated and had a similar safety profile to NPH insulin.

Topics: Aged; Analysis of Variance; Blood Glucose; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Weight Gain

Premixed insulin analogues reduce postprandial hyperglycemia in patients with Type 2 diabetes in comparison to premixed regular insulin. Insulin also plays an important role in the regulation of postprandial lipid metabolism. It is known that increased levels of postprandial insulin reduce postprandial hyperlipemia but, on the other hand, no information exists with regard to the possible effect of insulin analogues in comparison to human insulin.. 12 subjects (3 men; age 59 +/- 5 years; BMI 30.5 +/- 5.9 kg/m2, duration of diabetes 9 +/- 1 years, HbA1c 8.33 +/- 1.1 %) already on therapy with premixed insulin were treated either with biphasic human insulin (BHI30) or with biphasic insulin aspart (BIAsp30) (1.3 IU fast acting insulin/12 g KH) in the setting of a standardized test meal. Serum levels of glucose, insulin, C-peptide and triglycerides as well as retinylpalmitate in plasma and chylomicron remnants were determined before and up to 8 hours after the meal.. As was to be expected, therapy with BIAsp30 reduced the maximum increase of postprandial glucose from 7.10 +/- 2.00 mmol/l to 5.27 +/- 1.83 mmo/l (p = 0.007) compared to BHI30 insulin. In the same way, the maximum increase of triglycerides (from 2.33 +/- 1.03 to 1.65 +/- 0.69 mmol/l, p = 0.014) was reduced. The AUC 0 - 8 for triglycerides was not significantly influenced (34.20 +/- 19.86 vs. 31.46 +/- 16.21 mmol x 8 h/l) but the incremental area over baseline (AOB 0 - 8) was significantly reduced from 8.02 +/- 4.35 to 6.12 +/- 3.94 mmol x 8 h/l (p = 0.024).. Compared to conventional human premixed insulin the prandial therapy with biphasic insulin aspart results not only in an improvement of glucose tolerance but also in a significant reduction of postprandial hyperlipemia.

Topics: Biphasic Insulins; Chylomicron Remnants; Chylomicrons; Cross-Over Studies; Diabetes Mellitus, Type 2; Diterpenes; Female; Humans; Hyperlipidemias; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Postprandial Period; Retinyl Esters; Time Factors; Vitamin A

Topics: Adult; Blood Glucose; Body Mass Index; Carbamates; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin, Isophane; Male; Patient Dropouts; Piperidines

The medical literature supports the fact that sliding scale dosing of insulin is an ineffective means to control blood glucose concentrations. Despite this, many clinicians still use sliding scale insulin (SSI) regimens. A better tool for controlling hyperglycemia is clearly needed.. To compare the efficacy of an algorithm using 70/30 insulin with traditional SSI dosing for glycemic control in hospitalized patients with type 2 diabetes.. A prospective, cohort, comparative trial was conducted at a 644-bed, 2-hospital, regional referral health system. Patients were screened for enrollment based on orders received in the pharmacy for sliding scale dosing of insulin. Patients were treated either following an algorithm using 70/30 insulin twice daily or traditional SSI dosing as written by the prescribing physician.. Twenty patients with type 2 diabetes were involved in this pilot trial: 10 were treated with the 70/30 insulin algorithm and 10 received a physician-determined traditional SSI regimen. Patients treated based on the 70/30 insulin algorithm achieved better glycemic control (p = 0.042). No difference between the groups was detected in the average number of insulin units administered, insulin injections, or days patients spent on their respective insulin regimens.. Glycemic control with the 70/30 insulin algorithm was superior to traditional SSI dosing.

Topics: Algorithms; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Humans; Hypoglycemic Agents; Insulin; Insulin, Isophane; Treatment Outcome

Postprandial hyperglycemia contributes to glycation of hemoglobin A1c and has been associated with cardiovascular risk in people with diabetes. We investigated the impact of injection timing of Humalog Mix25 (Mix25, known as Humalog Mix75/25 in the U.S.: 25% insulin lispro and 75% neutral protamine lispro) on glycemia and postprandial blood glucose (BG) excursions in elderly individuals. Seventy-three patients aged 60 to 80 years were randomized to Mix25 (Mix25 group, 37 participants) or a continuation with maximum dose glibenclamide (control group, 36 participants). The Mix25 group was subdivided into a group of 18 patients who were injecting insulin after meals and 19 who were injecting before.. At baseline, the absolute postprandial BG concentrations and postprandial BG excursions after breakfast were high (Mix25 group: 15.3+/-4.8 mmol/l and 3.5+/-2.7 mmol/l, respectively; controls: 15.4+/-3.9 mmol/l and 4.7+/-2.7 mmol/l, respectively). In both groups improvement was observed at the endpoint, but it was greater with Mix25 (Mix25 group: 10.3+/-3.6 mmol/l, p<0.0001 vs. baseline, p<0.003 vs. controls, and 2.0+/-2.5 mmol/l, p<0.008 vs. baseline, p=ns vs. controls; control group: 13.3+/-2.9 mmol/l, p<0.006 vs. baseline, and 4.7+/-2.7 mmol/l, p<0.006 vs. baseline). The two Mix25 subgroups had similar postprandial BG levels and BG excursions after breakfast.. Mix25 improves postprandial BG and yields a greater effect on BG excursions compared with monotherapy with glibenclamide. The timing of Mix25 did not impact the level of BG or BG fluctuations after meals, which may be important for individuals with changing dietary pattern.

Topics: Aged; Aged, 80 and over; Biphasic Insulins; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glyburide; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Male; Middle Aged; Postprandial Period

Topics: Aged; Biphasic Insulins; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Postprandial Period

To evaluate the effects of insulin 30/70 twice daily or bedtime isophane (NPH) insulin plus continued sulfonylurea and metformin in patients with type 2 diabetes in primary care.. Open-label, randomized trial.. Persons younger than 76 years with type 2 diabetes whose disease had not been controlled with oral hypoglycemic agents alone. A total of 64 insulin-naive patients treated with maximal feasible dosages of sulfonylurea and metformin (baseline glycosylated hemoglobin [HbA1c]=8.5%) were randomly assigned to insulin monotherapy (IM group; n=31) or insulin in addition to unchanged oral hypoglycemic medication (IC group; n=33) for 12 months. Insulin doses were adjusted to obtain fasting glucose <7.0 mmol/L and postprandial glucose <10.0 mmol/L.. Outcome measures included HbA1c, treatment failure, weight, hypoglycemic events and symptoms, satisfaction with treatment, general well-being, and fear of injecting insulin and testing.. HbA1c improved from 8.3% to 7.6% in the IC group, and from 8.8% to 7.6% in the IM group (P=NS). The IC group had 24% treatment failures, compared with 2% in the IM group (P=.09). Patients in the IC group had less weight gain than those in the IM group (1.3 vs 4.2 kg; P=.01), and they reported fewer hypoglycemic events (2.7 vs 4.3; P=.02). Increased satisfaction with treatment was equal in the 2 groups, and general well-being improved by 3.0 points more in the IC group (P=.05). Fear of self-injecting and self-testing did not differ.. Bedtime NPH insulin added to maximal therapy with sulfonylurea and metformin is an effective, simple, well-tolerated approach for patients with uncontrolled type 2 diabetes.

Topics: Analysis of Variance; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin, Isophane; Male; Metformin; Middle Aged; Sulfonylurea Compounds

The goal of this study was to compare the efficacy and safety profiles of biphasic insulin aspart 30 (30% soluble insulin aspart and 70% protaminated insulin aspart [BIAsp 30]) and biphasic insulin lispro 25 (25% soluble insulin lispro and 75% neutral protamine lispro [Mix25]) used in a BID injection regimen in patients with type 2 diabetes mellitus (DM). Also assessed was patients' preference for pen device--the NovoMix 30 FlexPen /NovoLog Mix 70/30 FlexPen (FlexPen) versus the Humalog Mix25 Pen/Humalog Mix75/25 Pen (Humalog Pen).. Patients with type 2 DM receiving current insulin treatment were randomized to a multinational, multicenter, open-label, 2-period, crossover comparison of BIAsp 30 and Mix25. Efficacy (by analyses of variance) and safety profiles were assessed after 12 weeks of treatment. Patients' preference for pen device was assessed by questionnaires.. A total of 137 patients were randomized to treatment; 4 were withdrawn during the 2-week run-in treatment with biphasic human insulin 30. The mean (SD) characteristics of the remaining 133 patients (79 men, 54 women) were as follows: age, 62.3 (9.2) years; body mass index, 28.1 (3.9) kg/m(2); and glycosylated hemoglobin (HbA(1c)), 8.5% (1.1). Glycemic control was assessed by the measurement of HbA(1c) after 12 weeks of treatment. Treatment with BIAsp 30 was noninferior to treatment with Mix25 (upper limit of 90% CI for estimated difference [BIAsp 30 - Mix25] was <0.4%). Self-monitored blood glucose levels were comparable (P = NS). Adverse-event profiles were similar between treatments, as was the incidence of hypoglycemic episodes (0.69 episode/mo with BIAsp 30 and 0.62 episode/mo with Mix25, P = 0.292). For all device features assessed, the FlexPen consistently received higher scores (all P < 0.005). A total of 9.0% of patients experienced problems with the FlexPen, compared with 32.4% with the Humalog Pen (P < 0.001). Furthermore, 74.6% preferred to continue using the FlexPen, whereas 14.3% preferred the Humalog Pen (P < 0.001).. In this study, glycemic control with BIAsp 30 and Mix25 was found to be comparable in these patients with type 2 DM. Safety profiles were similar for both regimens. Patients preferred and experienced fewer problems with the FlexPen than the Humalog Pen.

Topics: Biphasic Insulins; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Disposable Equipment; Female; Glycemic Index; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Aspart; Insulin Lispro; Insulin, Isophane; Male; Middle Aged; Patient Satisfaction; Syringes; Treatment Outcome

Preprandial dosing (within 5 min before meal) and postprandial dosing (15-20 min after meal onset) of NovoLog Mix 70/30 (BIAsp 30, a biphasic formulation of insulin aspart, 30% soluble and 70% protamine-crystallized) were compared in elderly (> or =65 years) type 2 diabetes patients in this open-label, 12-week, crossover study. Ninety-three patients were treated with b.i.d. preprandial injections of BIAsp 30 during a 2-week run-in period and subsequently randomized to a 4-week treatment with either pre- or postprandial b.i.d. BIAsp 30, followed by crossover to the other regimen for 4 weeks. Mean plasma glucose values during a 4-h mealtest at the end of each treatment were similar for pre- and postprandial BIAsp 30 (153 +/- 58 mg/dl and 161 +/- 59 mg/dl, respectively, difference not significant). However, the mean blood glucose increment from self-measured blood glucose values was slightly but significantly greater after postprandial injection than after preprandial injection (treatment difference: 16.3mg/dl; 95% CI: [0.5, 29.3]). Fifty-six percent of patients reported a hypoglycemic episode; postprandial injection did not increase the incidence of hypoglycemia as compared to preprandial injection (113 episodes versus 125 episodes, respectively). For some elderly type 2 diabetes patients, postprandial injection of BIAsp 30 may be an acceptable alternative to standard preprandial injection.

Topics: Aged; Biomarkers; Biphasic Insulins; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Drug Administration Schedule; Eating; Female; Fructosamine; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Kinetics; Postprandial Period; Racial Groups; Safety

Insulin glulisine is a novel analog of human insulin designed for use as a rapid-acting insulin. This study compared the safety and efficacy of glulisine with regular human insulin (RHI) in combination with NPH insulin.. In total, 876 relatively well-controlled patients with type 2 diabetes (mean HbA1c 7.55%) were randomized and treated with glulisine/NPH (n = 435) or RHI/NPH (n = 441) for up to 26 weeks in this randomized, multicenter, multinational, open-label, parallel-group study. Subjects were allowed to continue the same dose of prestudy regimens of oral antidiabetic agent (OAD) therapy (unless hypoglycemia necessitated a dose change).. A slightly greater reduction from baseline to end point of HbA1c was seen in the glulisine group versus RHI (-0.46 vs. -0.30% with RHI; P = 0.0029). Also, at end point, lower postbreakfast (156 vs. 162 mg/dl [8.66 vs. 9.02 mmol/l]; P < 0.05) and postdinner (154 vs. 163 mg/dl [8.54 vs. 9.05 mmol/l]; P < 0.05) blood glucose levels were noted. Symptomatic hypoglycemia (overall, nocturnal, and severe) and weight gain were comparable between the two treatment groups. There were no between-group differences in baseline-to-end point changes in insulin dose.. Twice-daily glulisine associated with NPH can provide small improvements in glycemic control compared with RHI in patients with type 2 diabetes who are already relatively well controlled on insulin alone or insulin plus OADs. The clinical relevance of such a difference remains to be established.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemia; Injections, Subcutaneous; Insulin; Insulin, Isophane; International Cooperation; Male; Middle Aged; Probability; Reference Values; Risk Assessment; Severity of Illness Index; Single-Blind Method; Treatment Outcome

The optimal approach to relatively recent onset type 2 diabetes patients is still unknown. We speculated that the use of short-acting insulin analogs might be of particular benefit in this context.. To explore this possibility, we compared the effect on beta- and alpha-cell function of transient intensive insulin therapy using lispro versus human regular insulin in a total of 21 type 2 diabetic patients who were randomly assigned to 14-days intensive insulin therapy consisting of bedtime NPH insulin plus three injections of mealtime lispro (n=11) or regular insulin (n=10). The dosages of both types of insulin were adjusted to attain preprandial glucose levels of <6.1 mmol/l within 1 week with similar rates of glucose decline. An oral glucose tolerance test (OGTT) was performed at day 0 (baseline), 7, and 14; plasma glucose, serum insulin, and plasma glucagon responses over 0-120 minutes were measured, and calculated as the area under the curve (AUC).. Lispro led to a significant reduction in glucose-AUC and also an increase in insulin-AUC versus regular insulin on day 7. Glucagon secretion following OGTT was well suppressed with lispro on day 14 compared to regular insulin.. Two-week intensive insulin therapy with lispro appeared to be more effective than that with regular insulin in type 2 diabetes in attaining both more rapid beta-cell rest and greater suppression of glucagon. These changes may provide significant long-term benefits.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glucagon; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Lispro; Insulin, Isophane; Male; Middle Aged

The aim of the trial was to compare the efficacy and safety of the new, long-acting basal insulin, insulin glargine (LANTUS(R)), with NPH human insulin, each administered in a combination regimen with oral antidiabetic drugs in patients with Type 2 diabetes.. In a multicentre, open, randomised study, 570 patients with Type 2 diabetes, aged 34 - 80 years, were treated for 52 weeks with insulin glargine or NPH insulin given once daily at bedtime. Previous oral antidiabetic therapy was continued throughout the study.. There was a clinically relevant decrease in glycosylated haemoglobin (GHb) values from baseline to endpoint with both drugs (insulin glargine: - 0.46 %; NPH insulin: - 0.38 %; p = 0.415); also, this difference was statistically significant in the subgroup of overweight patients with BMI > 28 kg/m 2 (insulin glargine: - 0.42 %, NPH insulin: - 0.11 %; p = 0.0237). Over the entire treatment period, NPH insulin-treated patients (41 %) and insulin glargine-treated patients (35 %) experienced a similar level of symptomatic hypoglycaemia. A statistically significant difference was observed in the number of patients treated with NPH insulin who reported at least one episode of nocturnal hypoglycaemia compared with those treated with insulin glargine in the overall population and in the overweight subgroup (overall: 24 % vs. 12 %, p = 0.002; overweight: 22.2 % vs. 9.5 %, p = 0.0006), using the Cochran-Mantel-Haenszel test. These differences were most pronounced in insulin-naïve and overweight (BMI > 28 kg/m 2) sub-groups. The incidence of adverse events was similar for the two treatments.. This study demonstrated that insulin glargine is as effective as NPH insulin in achieving glycaemic control in patients with Type 2 diabetes, and is associated with fewer episodes of symptomatic hypoglycaemia, particularly nocturnal episodes.

Topics: Adult; Aged; Aged, 80 and over; Body Mass Index; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged

Patients with type 2 diabetes are often treated with oral antidiabetic agents plus a basal insulin.. To investigate the efficacy and safety of glimepiride combined with either morning or bedtime insulin glargine or bedtime neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes.. Open-label, randomized, controlled trial.. 111 centers in 13 European countries.. 695 patients with type 2 diabetes who were previously treated with oral antidiabetic agents.. Randomization to treatment with morning insulin glargine, bedtime NPH insulin, or bedtime insulin glargine for 24 weeks in addition to 3 mg of glimepiride. The insulin dose was titrated by using a predefined regimen to achieve fasting blood glucose levels of 5.56 mmol/L or lower (< or =100 mg/dL).. Hemoglobin A(1c) values, blood glucose levels, insulin dose, and body weight.. Hemoglobin A(1c) levels improved by -1.24% (two-sided 90% CI, -1.10% to -1.38%) with morning insulin glargine, by -0.96% (CI, -0.81% to -1.10%) with bedtime insulin glargine, and by -0.84% (CI, -0.69% to -0.98%) with bedtime NPH insulin. Hemoglobin A(1c) improvement was more pronounced with morning insulin glargine than with NPH insulin (0.40% [CI, 0.23% to 0.58%]; P = 0.001) or bedtime insulin glargine (0.28% [CI, 0.11% to 0.46%]; P = 0.008). Baseline to end-point fasting blood glucose levels improved similarly in all three groups. Nocturnal hypoglycemia was less frequent with morning (39 of 236 patients [17%]) and bedtime insulin glargine (52 of 227 patients [23%]) than with bedtime NPH insulin (89 of 232 patients [38%]) (P < 0.001).. The risk for nocturnal hypoglycemia was lower with glimepiride in combination with morning and bedtime insulin glargine than with glimepiride in combination with bedtime NPH insulin in patients with type 2 diabetes. Morning insulin glargine provided better glycemic control than did bedtime insulin glargine or bedtime NPH insulin.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Risk Factors; Sulfonylurea Compounds; Weight Gain

This study set out to define relationships between changes in plasma leptin and changes in body weight, plasma insulin and blood glucose control during a 12-month crossover study of once-daily Ultratard or twice-daily Insulatard insulin.. Fasting plasma leptin and insulin were measured during a multicentre cross-over study involving 60 subjects with type 2 diabetes (fasting glucose > 8 mM). After a 2-month run-in, there were two 6-month periods of treatment with Insulatard or Ultratard insulin.. Mean plasma leptin increased significantly in both groups after insulin therapy was instigated (12.8 +/- 8.1 to 22.9 +/- 13.1 ng/ml in the Insulatard group; 12.1 +/- 7.2 to 19.2 +/- 12.3 ng/ml in the Ultratard group). Weight also increased significantly in both groups (82.4 +/- 14.3 kg to 88.8 +/- 14.3 kg and 82.2 +/- 15.3 kg to 85.3 +/- 15.2 kg respectively). The increase in plasma leptin correlated well with the increase in weight (R = 0.416, p = 0.001), and this correlation continued after the crossover point. Plasma leptin correlated with BMI throughout the study (R = 0.540, p = 0.000).. The sustained rise in body weight despite a substantial increase in plasma leptin suggests that either resistance to the hypothalamic action of leptin develops when insulin therapy is begun in type 2 diabetes, or that resetting of the set point for body weight occurs such that a larger body mass is tolerated for a given level of plasma leptin.

Topics: Body Mass Index; Body Weight; Cross-Over Studies; Diabetes Mellitus, Type 2; Fasting; Female; Glycated Hemoglobin; Humans; Insulin; Insulin, Isophane; Insulin, Long-Acting; Insulin, Regular, Human; Isophane Insulin, Human; Leptin; Male; Middle Aged

The aim of this study was to compare the subcutaneous absorption characteristics of insulin glargine with NPH insulin in patients with Type 2 diabetes. In this single-dose, double-blind, randomized, two-way crossover study, 14 patients with Type 2 diabetes (aged 40-70 years) previously untreated with insulin were randomized to receive in a fasting state either a single subcutaneous injection of 0.3 U/kg 125I-insulin glargine or 0.3 U/kg 125I-NPH insulin. The disappearance of radioactivity was monitored for forty-eight hours. The median time for 25%, 50% and 75% of the radioactivity to disappear from the injection site was significantly longer for insulin glargine compared with NPH insulin (T75% 15.0 and 6.5 h, p=0.009; T50% 26.3 and 13.4 h, p=0.009; T25% 42.4 and 26.6 h, p=0.019, respectively). The mean residual radioactivity remaining at 24, 36 and 48 h after injection remained significantly higher than NPH insulin (54.4 and 27.9%, p=0.0001; 35.0 and 17.0%, p=0.003; 19.2 and 9.2%, p=0.01, respectively). Mean plasma glucose levels reached a minimum after 14.6 and 9 h in response to insulin glargine and NPH insulin, respectively. The subcutaneous absorption of insulin glargine in fasting Type 2 diabetes patients was significantly (2-3 times) slower compared with NPH insulin in patients with Type 2 diabetes. The slower absorption of insulin glargine correlated with the fall in plasma glucose levels over a 24 h period compared with the faster insulin absorption and more rapid decrease in plasma glucose levels observed in response to NPH insulin. Both insulin glargine and NPH insulin were well tolerated.

Topics: Adult; Aged; Blood Glucose; C-Reactive Protein; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Half-Life; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Iodine Radioisotopes; Middle Aged; Scintillation Counting; Skin Absorption

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Aspirin; Behavior Therapy; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Dietary Carbohydrates; Dietary Fats; Exercise; Humans; Insulin, Isophane; Losartan; Risk Factors; Smoking Cessation

To compare the abilities and associated hypoglycemia risks of insulin glargine and human NPH insulin added to oral therapy of type 2 diabetes to achieve 7% HbA(1c).. In a randomized, open-label, parallel, 24-week multicenter trial, 756 overweight men and women with inadequate glycemic control (HbA(1c) >7.5%) on one or two oral agents continued prestudy oral agents and received bedtime glargine or NPH once daily, titrated using a simple algorithm seeking a target fasting plasma glucose (FPG)

Topics: Administration, Oral; Adult; Aged; Algorithms; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome

Nonfasting plasma glucose is claimed to be a better marker of diabetic control than fasting plasma glucose in type 2 diabetes. In this study we compared the efficacy and safety profile of two different intensive insulin treatment strategies in patients with uncontrolled type 2 diabetes despite using a twice-daily insulin regimen.. We studied 60 insulin-treated patients who had uncontrolled type 2 diabetes. The study was a 6-month, open-label, randomised, parallel clinical trial conducted in two diabetes centres. The main end-points for analysis were weekly self-monitored blood glucose readings, HbA1c levels, total daily insulin dose, weight gain and the number of hypoglycaemic episodes.. The breakfast 2-h, lunch 2-h and dinner 2-h postprandial glucose values and pre-dinner glucose values were significantly lower in the Lispro group than the regular insulin group. The HbA1c value at the end of the study was significantly lower in the Lispro group (7.3 +/- 0.7%) compared with the regular insulin group (7.7 +/- 0.7%; P<0.05). Mean insulin doses were similar in the treatment groups initially and at the end. There was a statistically significant increase in insulin dose in both groups from baseline to the end of the study (P<0.05). Overall hypoglycaemia rates were comparably low and similar in both groups during the study.. We have shown that mealtime insulin Lispro plus additional lunch and bedtime NPH insulin is superior to premeal regular insulin plus bedtime NPH insulin for overall glycaemic regulation with similar weight gain and comparable rates of hypoglycaemia.

Topics: Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Drug Administration Schedule; Eating; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Middle Aged; Safety; Time Factors; Treatment Outcome

It has been found that non-fasting plasma glucose is a better marker of diabetic control than fasting plasma glucose in type 2 diabetes. The main aim of treatment of type 2 diabetic patients is to control plasma glucose and HbA1c levels. In this study, we aimed to assess the effects of three different insulin regimens (group I: lispro insulin + NPH insulin, group II: lispro insulin + metformin and group III: regular insulin + NPH insulin) on overall glycaemic control and metabolic parameters in type 2 diabetic patients with secondary oral anti-diabetic drug failure.. Sixty type 2 diabetic patients with secondary OAD failure were randomly allocated into three different treatment groups equally. There were no significant differences between groups concerning age, body mass index, diabetes duration, HbA1c and serum lipid levels at the beginning of the study. During the 6-month treatment period, blood glucose levels were determined 10 times during 24 h at pre-meal, post-prandial 1 and 2 h and at bedtime.. Group I was found to be the most effective treatment regimen in controlling HbA1c levels (group I vs. group II, p = 0.013; group I vs. group III, p = 0.001; group II vs. group III, p > 0.05). When the comparison was made in each group, change in HbA1c was statistically significant for all groups (-3.18%, p = 0.001; -2.02%, p = 0.043 and -2.66%, p = 0.008 respectively). Group I was found to be more effective in controlling fasting and post-prandial plasma glucose levels measured at all times during the day when compared with group II and group III. In group II triglyceride levels were found to be significantly reduced, whereas other groups had no effect on lipids. No serious hypoglycaemic episodes were observed in any of the cases, whereas in group I hypoglycaemic episode rates were increased (chi2 = 8.843, p = 0.012).. Lispro insulin plus NPH insulin regimen is more effective in controlling both pre- and post-prandial glucose levels and HbA1c when compared to regular insulin plus NPH insulin combination. Mealtime lispro insulin plus metformin combination therapy should also be seriously considered as an effective and alternative treatment regimen. It is worthy of attention that insulin lispro plus metformin lowered triglyceride levels.

Topics: Administration, Oral; Adult; Aged; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Metformin; Middle Aged; Postprandial Period; Prospective Studies; Treatment Failure

Biphasic insulin aspart 30 (BIAsp30) is a dual release formulation, containing 30% soluble and 70% protamine-crystallized insulin aspart. This study compared the glycaemic control and safety profiles achieved with either twice daily BIAsp30 or NPH insulin in patients with type 2 diabetes not optimally controlled by oral hypoglycaemic agents (OHAs), NPH insulin or a combination of both.. In this 16-week multinational, parallel-group, double-blind trial, 403 such patients were randomized to receive either BIAsp30 or NPH insulin immediately before breakfast and evening meals. OHAs were discontinued at randomization. Efficacy was assessed by glycosylated haemoglobin (HbA1c) and self-recorded daily 8-point blood glucose (BG) profiles. Hypoglycaemic and other adverse events were the chosen safety parameters.. HbA1c concentration decreased by >0.6% (p < 0.0001 vs. baseline) in both groups, with metabolic control continuing to improve throughout the trial without reaching a stable level. Patients who switched from once or twice daily NPH monotherapy to twice daily BIAsp30 achieved a significantly greater reduction in HbA1c (0.78%) than those randomized to twice daily NPH insulin (0.58%; p = 0.03). BIAsp30 decreased mean daily postprandial glycaemic exposure to a greater extent than NPH insulin (mean difference = 0.69 mmol/l; p < 0.0001), reflecting greater decreases in the postbreakfast and postdinner increments (of 1.26 and 1.33 mmol/l, respectively), although postlunch increment was relatively increased (by 0.56 mmol/l). Despite the greater reduction in overall postprandial glycaemic exposure in the BIAsp30 group, the overall safety profile of BIAsp30 was equivalent to that of NPH insulin with <2% of patients experiencing major hypoglycaemia, and approximately 33% reporting minor hypoglycaemic episodes, in both groups.. Twice daily BIAsp30 reduced postprandial glucose exposure to a significantly greater extent than NPH insulin and was at least as effective at reducing HbA1c in patients with type 2 diabetes. Both insulins were well tolerated. In patients poorly controlled on OHAs or NPH alone, glycaemic control can be improved by switching to twice daily BIAsp30, without increasing hypoglycaemic risk.

Topics: Adult; Aged; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Administration Schedule; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Postprandial Period; Treatment Outcome

This open-label randomized controlled clinical trial compared the effect on glycaemic control and weight gain of repaglinide vs. gliclazide combined with bedtime NPH insulin in patients with Type 2 diabetes inadequately controlled with oral hypoglycaemic therapy [HbA1c>7.0% (DCCT aligned assay, normal range 4.6-6.2%)].. Eighty subjects with Type 2 diabetes were randomized to 13 weeks' open-label treatment with repaglinide 4 mg t.i.d. or gliclazide 160 mg b.i.d. in combination with bedtime NPH insulin (initial dose 0.5 units/kg). The fasting blood glucose (FBG) target was < or =6.0 mmol/l.. Baseline characteristics were similar for age, sex, weight, BMI, FBG and HbA1c. Glycaemic control improved similarly in both groups-insulin/gliclazide by (mean) 1.0%, from 9.2 to 8.2% (P=0.001) and by 0.9%, from 9.4 to 8.5% in the insulin/repaglinide group (P=0.005) (P=0.83 between groups). Weight gain averaged (mean +/- sem) 4.1 +/- 0.5 and 3.4 +/- 0.4 kg in the insulin/gliclazide and insulin/repaglinide groups, respectively (P<0.0001 for both groups from baseline) (P=0.29 between groups). The mean number of hypoglycaemic episodes experienced per patient was 2.95 +/- 0.82 (insulin/gliclazide) and 2.3 +/- 0.52 (insulin/repaglinide) (P=0.81 between groups). Both treatments were associated with significant improvements in Diabetes Treatment Satisfaction [Diabetes Treatment Satisfaction Questionnaire-potential range 0 (min) to 36 (max)]; in the insulin/gliclazide group, by 4.9 +/- 1.1 points to 33.3 +/- 0.6 (P<0.0001) and by 3.0 +/- 0.9 points to 34.6 +/- 0.4 (P=0.0006) in the insulin/repaglinide group (P=0.29 between groups).. Over 13 weeks, both repaglinide and gliclazide, when combined with bedtime NPH insulin produce similar significant improvements in glycaemic control (-1%) and similar weight gain.

Topics: Administration, Oral; Blood Glucose; Carbamates; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Gliclazide; Hemoglobin A; Humans; Hypoglycemic Agents; Insulin, Isophane; Male; Metformin; Middle Aged; Patient Satisfaction; Piperidines; Surveys and Questionnaires; Weight Gain

We investigated the use, in a short period, of Humalog Mix25 (Mix25) in a twice-daily administration regimen compared to a twice-daily injection therapy with Humulin 30/70 (30/70) in diabetic patients with Italian dietary habits. We studied 33 type 2 diabetic patients aged 59.1 +/- 8.1 years, BMI 29.8 +/- 2.7 kg/m2, duration of diabetes and insulin therapy of 14.4 +/- 9.8 and 4.2 +/- 4.6 years, respectively. After a 4-day lead-in period of twice-daily human insulin 30/70 treatment, patients were randomized to one of two treatment sequences: (1) a twice-daily regimen with Mix25 just 5 minutes before the morning and evening meals for 12 days, followed by a twice-daily therapy with human insulin 30/70 given 30 minutes before the morning and evening meals for an additional 12 days; or (2) the alternate sequence. Each patient underwent a mixed meal test: Humulin 30/70 was administered 30 minutes before the meal, while Mix25 was given 5 minutes before. The 2-hour post-prandial glucose concentration after breakfast was significantly lower during treatment with Mix25 than with Humulin 30/70 (157 +/- 43.2 vs. 180 +/- 43.2 mg/dl, p<0.05). The glycemic excursion after dinner on Mix25 treatment was significantly lower than with Humulin 30/70 (12.2 +/- 48.01 vs. 35.5 +/- 36.92 mg/dl, p<0.05). AUCglucose after Mix25 was lower than after Humulin 30/70. Glycemia after test meal was significantly lower with Mix25 than with Humulin 30/70. Insulin and free insulin concentrations after the test meal were significantly higher with Mix25 in comparison to Humulin 30/70. AUC serum insulin and free insulin curves after Mix25 were significantly higher than after Humulin 30/70 (p=0.028 and p=0.005, respectively). Twice-daily injections of Humalog Mix25, compared to human insulin 30/70 in type 2 diabetic patients with Italian dietary habits, provide improved and lasting post-prandial glycemic control, with the great convenience of the injection just before the meal.

Topics: Biphasic Insulins; Cross-Over Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Administration Schedule; Eating; Feeding Behavior; Female; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Lispro; Insulin, Isophane; Italy; Male; Middle Aged; Research Design; Time Factors

The incidence of type 2 diabetes mellitus (DM) is rapidly increasing worldwide. Results from large-scale studies show that tight blood glucose (BG) control improves the outcome of patients with type 2 DM.. This trial assessed the short-term efficacy and tolerability of adding a thiazolidinedione (rosiglitazone [ROS]) to existing sulfonylurea (SU) therapy (glibenclamide) compared with switching to combination treatment with a premixed insulin (biphasic insulin aspart 30 [BIAsp 30], a rapid-acting insulin analog) and the thiazolidinedione in a select group of patients with type 2 DM whose metabolic control was inadequate with SU monotherapy.. In this 6-week, multicenter, open-label, parallel-group trial, patients with type 2 DM whose BG level was not adequately controlled with glibenclamide monotherapy (glycosylated hemoglobin [HbA1c] 8%-13%) were randomized either to replace glibenclamide with BIAsp 30 (individually titrated dosages starting with 6-8 U BID) plus rosiglitazone (4 mg once daily) (BIAsp 30 + ROS group) or to add rosiglitazone (4 mg once daily) to their pretrial doses of glibenclamide (GLIB + ROS group). Patients measured their BG levels immediately before each of the 3 main meals, 90 minutes after the start of each meal, and at bedtime, and mean BG levels were calculated at weeks 0 (baseline), 1, 2, 4, 6, and at 2-week follow-up (week 8). The primary end point was change in mean daily BG level during treatment. Secondary end points included preprandial, postprandial, and bedtime BG levels, serum fructosamine level HbA, and fasting BG level, which were measured at each study visit. Tolerability was assessed using hematologic and biochemical parameters, vital signs, and physical examination.. Forty-nine patients (32 men, 17 women; mean [SD] age, 59.1 [8.9] years; mean [SD] body mass index, 27.7 [3.7] kg/m2) participated in the study. A significant difference was found between treatments in the change in mean daily BG level from baseline to week 6 (P=0.01). After the 6-week treatment period, change in mean serum fructosamine level was significantly greater for BIAsp 30 + ROS compared with GLIB + ROS (P=0.02). HbA1c decreased in both treatment groups from baseline to study end, but the difference between groups was nonsignificant. The changes in fasting BG from baseline to study end also were nonsignificant between groups. Both combinations were well tolerated.. This short-term study in patients with type 2 DM whose BG level was poorly controlled with glibenclamide monotherapy suggests that switching to a combination of BIAsp 30 + ROS was efficacious and well tolerated and provided an alternative to adding rosiglitazone to existing glibenclamide treatment. The study also suggests that BIAsp 30 may be associated with greater improvements in short-term metabolic control.

Topics: Adult; Aged; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Fructosamine; Glyburide; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Rosiglitazone; Thiazolidinediones; Treatment Outcome

Humalog Mix 25 (Mix 25) is a premixed insulin mixture of 25% lispro and 75% neutral protamine lispro. Insulin lispro is an analog of human insulin. It is created when the amino acids at positions 28 and 29 of the B-chain of insulin are reversed. The natural sequence in human insulin at this position is proline at B28 and lysine at B29. The pharmacokinetic and pharmacodynamic profiles of insulin lispro indicate that it is more rapid acting, and therefore more physiological mealtime insulin than regular human insulin.. Primary objective of this study was to compare twice daily treatment with insulin lispro low mixture (Mix 25) to oral treatment with glibenclamide in patients with type 2 diabetes, with respect to the mean 2-hour postprandial blood glucose excursions after breakfast and dinner.. to compare the two treatments with regard to the following: hemoglobin A1c, fasting blood glucose, pre-dinner blood glucose, frequency of hypoglycemia, body weight, treatment satisfaction (by questionnaire).. The study described is a randomized, open-label, parallel group comparison of two treatment regimens in patients with type 2 diabetes. The study included two periods. The lead-in period lasted 10 +/- 7 days, all patients were taking glibenclamide. The treatment period lasted 16 weeks. Patients were randomized to receive either glibenclamide 15 mg daily or switch to Mix 25 before breakfast and dinner. Study design is illustrated in Fig. 1. Glycemic control was assessed by glycosylated hemoglobin (HbA1c) measurements, 4-point self monitoring blood glucose profiles, and patient reported hypoglycemia. One treatment satisfaction questionnaire (Appendix 1) was completed by each participant.. 175 patients were included from the two participating countries (Romania--100 patients and Russia--75 patients). 85 were randomized to receive Mix 25 and 90 to glibenclamide arm. 172 patients were included in the efficacy analysis. Baseline patient characteristics did not show any differences between treatment groups for any of the demographic (age, gender, height, body weight, body mass index) or efficacy parameters (HbA1c or self monitored BG values). The mean age was 59.5 +/- 8.2 years, and 35.5% (61/172) were men. The mean body mass index was 27.2 kg/m2. The mean duration of type 2 diabetes was 10.2 +/- 6.6 years, and the mean duration of sulfonylurea treatment was 5.8 +/- 5.9 years. The mean HbA1c and fasting blood glucose levels were 10.07 +/- 1.4% and 11.6 +/- 2.8 mmol/L, respectively, in the glibenclamide group and 9.85 +/- 1.2% and 12.2 +/- 2.9 mmol/L, respectively, in the Mix 25 group. At the end point, all efficacy parameters were better improved in Mix 25 group (HbA1c, fasting blood glucose, 2-hour postprandial blood glucose). Mean HbA1c was significantly lower in the Mix 25 group than in the GB group (Mix 25, 8.5% +/- 1.3%; GB, 9.4 +/- 1.8%; P = 0.001). For all self-monitored blood glucose values (Fig. 2) a larger decrease from baseline was observed in the Mix 25 group: -1.4% versus -0.7% for HbA1c, (P = 0.004); -2.8 mmol/L versus -1.1 mmol/L for fasting blood glucose, (P < 0.01); -5.1 mmol/L versus -1.7 mmol/L for the morning 2-hour postprandial blood glucose, (P < 0.001); -2.2 mmol/L versus -0.8 mmol/L for the evening preprandial blood glucose, (P < 0.05); and 4.4 mmol/L versus -1.5 mmol/L for the evening 2-hour postprandial blood glucose, (P < 0.001). Percentage of patients experiencing at least 1 episode of hypoglycemia was--as predicted--higher in the Mix 25 group (44.7% versus 10.3%; P = 0.01). Patients expressed more satisfaction with Mix 25 than with GB, as measured by the weighted combined score on a treatment satisfaction questionnaire (2.0 +/- 1.3 vs 0.7 +/- 1.3).. When glycemic control can no longer be achieved by oral antidiabetic agents, treatment with insulin should be considered as the next therapeutic option. Mix 25 provided good overall glycemic control, as well as patient treatment satisfaction.

Topics: Administration, Oral; Adult; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glyburide; Humans; Hypoglycemic Agents; Injections; Insulin; Insulin Lispro; Insulin, Isophane; Male; Middle Aged; Patient Satisfaction; Postprandial Period; Treatment Outcome

To compare the effect on glycemic control and weight gain of repaglinide versus metformin combined with bedtime NPH insulin in patients with type 2 diabetes.. A total of 80 subjects treated with 850 or 1,000 mg t.i.d. metformin combined with bedtime NPH insulin were randomized to 13 weeks of open-label treatment with 4 mg t.i.d. repaglinide (n = 39) or metformin (dose unchanged) (n = 41). Insulin dose was titrated at the clinician's discretion, aiming for a fasting blood glucose (FBG) < or =6.0 mmol/l.. Baseline age, diabetes duration, insulin requirement, weight, BMI, FBG, and HbA(1c) (Diabetes Control and Complications Trial-aligned assay, normal range 4.6-6.2%) were similar. Glycemic control improved (nonsignificantly) with insulin/metformin by (mean) 0.4%, from 8.4 to 8.1% (P = 0.09) but deteriorated with insulin/repaglinide by (mean) 0.4%, from 8.1 to 8.6% (P = 0.03; P = 0.005 between groups). Weight gain was less with insulin/metformin: 0.9 +/- 0.4 kg (means +/- SE) (P = 0.01) versus 2.7 +/- 0.4 kg (P < 0.0001) (P = 0.002 between groups). The Diabetes Treatment Satisfaction Questionnaire score (potential range 0 [minimum] to 36 [maximum]) increased from 32.4 +/- 0.8 to 34.1 +/- 0.5 (P = 0.01) with insulin/metformin but decreased from 32.5 +/- 0.9 to 29.1 +/- 1.3 (P < 0.002) with insulin/repaglinide.. Combined with bedtime NPH insulin, metformin provides superior glycemic control to repaglinide with less weight gain and improved diabetes treatment satisfaction.

Topics: Blood Glucose; Carbamates; Creatinine; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Insulin, Isophane; Male; Metformin; Middle Aged; Piperidines; Time Factors

To study the effect on body weight and glycaemic control of two insulin treatment regimens in patients with Type 2 diabetes and moderate failure to oral hypoglycaemic agents.. Sixteen patients treated with oral hypoglycaemic agents (6 men and 10 women) were included in this open-label, randomized, parallel group study. Their age was 62 +/- 2 (mean +/- SEM) years (range 44-79 years), body weight 71.3 +/- 2.9 kg, body mass index (BMI) 24.6 +/- 0.8 kg/m(2). The patients were switched to insulin treatment with bedtime NPH insulin combined with daytime sulphonylurea (combination group) or twice daily injections of a premixed combination of regular human and NPH insulin (insulin twice daily group) with measurements as given below before and after 12 and 24 weeks of treatment.. HbA(1c) was lowered from 8.3 +/- 0.3% to 7.0 +/- 0.2% in the insulin twice daily group (p<0.05) and from 8.3 +/- 0.3% to 6.8 +/- 0.5% in the combination group (p<0.03; ns between treatment groups). Body weight increased from 71.7 +/- 4.0 kg to 77.6 +/- 4.4 kg in the insulin twice daily group (p<0.001) and from 70.8 +/- 4.6 kg to 72.7 +/- 5.1 kg in the combination group (ns; p<0.02 between groups). The dose of insulin at 24 weeks in the insulin twice daily group was 45.8 +/- 4.2 U and 29.4 +/- 5.4 U in the combination group (p=0.03). Combination treatment reduced fasting and stimulated C-peptide levels.. Both treatments improved glycaemic control to the same extent but the combination of bedtime NPH insulin and daytime sulphonylurea gave a very small increase of body weight over a 6 months period. We conclude that combination therapy is an attractive alternative when starting insulin treatment in patients with Type 2 diabetes as this is a critical period for weight gain in such patients.

Topics: Administration, Oral; Adult; Aged; Blood Glucose; Body Mass Index; Body Weight; C-Peptide; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Insulin, Isophane; Middle Aged; Sulfonylurea Compounds; Weight Gain

The rapid-acting insulin analogs aspart and lispro have now been developed in biphasic formulations. This trial compared the postprandial serum glucose control of biphasic insulin aspart 30 (BIAsp 30: 30% aspart, 70% protaminated aspart) with that of biphasic insulin lispro 25 (Mix25: 25% lispro, 75% protaminated lispro) and biphasic human insulin 30 (BHI 30: 30% regular insulin, 70% NPH insulin) in insulin-treated subjects with type 2 diabetes.. This was an open-labeled, randomized, single-dose, three-way crossover trial of 61 insulin-treated subjects with type 2 diabetes who had no significant late diabetic complications. BIAsp 30 and Mix25 were injected subcutaneously immediately before a test meal, and BHI 30 was injected 15 min before a test meal. The primary target of analysis was serum glucose excursion 0-5 h after a meal.. The postprandial glycemic control with BIAsp 30, as assessed by the 5-h postmeal serum glucose excursion, was superior to that with both BHI 30 and Mix25 (16.6 +/- 4.5 vs. 20.1 +/- 4.9 and 18.9 +/- 6.1 mmol/l per hour, respectively; P < 0.001 and P < 0.05). For BIAsp 30 versus BHI 30, this was supported by a reduced maximum glucose concentration [C(max(SG))] (-5%; P < 0.05) occurring earlier (-13 min; P < 0.01). Furthermore, BIAsp 30 displayed a higher maximum serum insulin concentration (+101%; P < 0.001) occurring earlier (-55 min; P < 0.001) compared with BHI 30. Compared with Mix25, there was a shorter time to C(max(SG)) (-11 min; P < 0.05) after treatment with BIAsp 30.. This trial demonstrates that BIAsp 30 improves postprandial glycemic control compared with both Mix25 and BHI 30 in subjects with type 2 diabetes.

Topics: Adult; Aged; Aged, 80 and over; Biphasic Insulins; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Lispro; Insulin, Isophane; Male; Middle Aged; Postprandial Period; Treatment Outcome

The purpose of this study was to compare the pharmacokinetics and pharmacodynamics of the premixed insulin analogue biphasic insulin aspart (BIAsp 30) with the equivalent premixed biphasic human insulin (BHI 30), administered twice daily, in patients with type 2 diabetes mellitus.. In this randomized, double-blind, crossover trial, 13 patients (mean age, 64 years; baseline mean glycosylated hemoglobin, 7.7%; mean body mass index, 28.1 kg/m2) received 2 weeks of treatment with BIAsp 30 and 2 weeks of BHI 30 administered immediately before dinner and breakfast. At the end of each 2-week treatment period, 24-hour serum insulin and glucose profiles were determined using specific 2-sided enzyme-linked immunosorbent assays. All pharmacodynamic and pharmacokinetic end points were analyzed using analysis of variance.. Total daily insulin exposure was similar between treatment periods. Mean area under the total insulin concentration-time profile during the 2 hours following administration of BIAsp 30 was 17% greater than that of BHI 30 after dinner and 44% greater after breakfast; both differences were statistically significant. The maximum serum insulin aspart concentrations following BIAsp 30 were significantly higher after dinner (18%) and breakfast (35%). Peak serum insulin concentration was reached 1 hour earlier after breakfast and 45 minutes earlier after dinner in the BIAsp 30 group; differences were significant only after breakfast. The mean daily prandial glucose excursion was significantly lower for BIAsp 30 (16.2 mmol x h x L(-1)) than BHI 30 (17.9 mmol x h x L(-1)). Postprandial 4-hour glucose excursions were significantly lower with BIAsp 30 than with BHI 30 after dinner and breakfast, but were significantly greater after lunch. Mean 24-hour and nocturnal serum glucose concentrations were similar, and both insulins were associated with < or = 7 minor and no major hypoglycemic events.. Premeal injection of BIAsp 30 in a twice-daily regimen significantly reduced overall postprandial glucose excursions. This effect may be of importance when improvement in postprandial glucose control is desired.

Topics: Adult; Aged; Area Under Curve; Biphasic Insulins; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged

To compare the efficacy and safety of premixed insulin aspart (30% free and 70% protamine-bound, BIAsp 30) with human insulin premix (BHI 30) used in a twice-daily injection regimen in people with Type 1 and Type 2 diabetes.. People with Type 1 and Type 2 diabetes (n = 294) using twice-daily insulin were randomized to a 12-week open-label comparison of BIAsp 30 and BHI 30. Efficacy was assessed by analysis of variance of 12-week data, adjusted for baseline level.. BIAsp 30 was as effective as BHI 30 based on the primary efficacy measure, HbA1c, mean difference -0.01 (90% confidence interval (CI) -0.14; 0.12) %Hb. Meal-time self-measured blood glucose increment averaged over the three main meals was significantly lower in the BIAsp 30 group than in the BHI 30 group (-0.68 (-1.20; -0.16) mmol/l; P < 0.02). Significant improvements were observed after breakfast, before lunch, after dinner and at bedtime (P < 0.02-0.05), with blood glucose around 1.0 mmol/l lower in the BIAsp 30 group. The number of major hypoglycaemic episodes with BIAsp 30 was half that with BHI 30. However, the overall risk of both minor and major hypoglycaemia did not differ significantly between treatments.. Post-prandial glycaemic control was significantly improved, without increasing the risk of hypoglycaemia, and overall control was similar when people with Type 1 and Type 2 diabetes were treated on a twice-daily regimen with immediate premeal injections of BIAsp 30 compared with BHI 30.

Topics: Adult; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Combinations; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged

Combination therapy of oral hypoglycaemic agents and insulin is a therapeutic option for those who have deterioration in glycaemic control. We examined the contribution of metformin by withdrawing it from Type 2 diabetic patients who had been stabilised on combination therapy. Fifty-one subjects with Type 2 diabetes and secondary oral hypoglycaemic agent failure were studied in a randomised, open and parallel study. In the first phase of 36 weeks, subjects were stabilised on combined therapy of sulphonylureas and nocturnal insulin, with or without metformin. During the second phase, metformin was withdrawn. The primary variables for efficacy were HbA(1c), fasting plasma glucose and 3-point capillary blood glucose profiles. After stabilisation with combination therapy, those subjects on metformin used less insulin to maintain glycaemic control (13.7+/-6.8 vs. 23.0+/-9.4 U/day, P=0.001) and had lower HbA(1c) values (8.13+/-0.89 vs. 9.05+/-1.30%, P=0.003) compared with those not given metformin. Withdrawal of metformin therapy caused deterioration in HbA(1c) (P=0.001). This study confirms that metformin plays an important role in the success of the combination therapy. The rational use of metformin and sulphonylurea together with insulin will help to improve metabolic control in Type 2 diabetes patients who have secondary drug failure.

Topics: Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Fasting; Female; Humans; Hypoglycemic Agents; Insulin, Isophane; Male; Metformin; Middle Aged; Postprandial Period; Sulfonylurea Compounds

To determine the safety and efficacy of the long-acting analog insulin glargine compared with NPH insulin in patients with type 2 diabetes who were previously treated with insulin alone.. A total of 518 subjects with type 2 diabetes who were receiving NPH insulin with or without regular insulin for postprandial control were randomized to receive insulin glargine (HOE 901) once daily (n = 259) or NPH insulin once or twice daily in = 259) for 28 weeks in an open-label, multicenter trial. Doses were adjusted to obtain target fasting glucose <6.7 mmol/l. At study end point, the median total daily insulin dose in both treatment groups was 0.75 IU/kg.. The treatment groups showed similar improvements in HbA1c from baseline to end point on intent-to-treat analysis. The mean change (means +/- SD) in HbA1c from baseline to end point was similar in the insulin glargine group (-0.41 +/- 0.1%) and the NPH group (-0.59 +/- 0.1%) after patients began with an average baseline HbA1c of approximately 8.5%. The treatments were associated with similar reductions in fasting glucose levels. Overall, mild symptomatic hypoglycemia was similar in insulin glargine subjects (61.4%) and NPH insulin subjects (66.%) However, nocturnal hypoglycemia in the insulin glargine group was reduced by 25% during the treatment period after the dose-titration phase(26.5 vs. 35.5%, P = 0.0136). Subjects in the insulin glargine group experienced less weight gain than those in the NPH group (0.4 vs. 1.4 kg, P < 0.0007).. In patients with type 2 diabetes, once-daily bedtime insulin glargine is as effective as once- or twice-daily NPH in improving and maintaining glycemic control. In addition, insulin glargine deonstrates a lower risk of nocturnal hypoglycemia and less weight gain compared with NPH insulin.

Topics: Blood Glucose; Body Mass Index; Circadian Rhythm; Diabetes Mellitus, Type 2; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Postprandial Period; Risk Factors; Time Factors

Strict glycaemic control in type 2 diabetic patients is recommended in a number of treatment protocols. However, although better glycaemic control prevents or postpones chronic diabetic complications, it remains uncertain how this affects quality of life in the short and long term.. To study the impact of insulin therapy on glycaemic control and quality of life in type 2 diabetic patients, with secondary failure on maximal oral medication.. Two separate sets of analyses were performed: a longitudinal analysis of those patients converted to insulin therapy and a comparison of 12-week outcomes between the two randomisation groups.. Ten general practices, participating in the Nijmegen Monitoring Project.. Patients, poorly controlled on maximal oral therapy, were stratified with respect to age and sex, and randomly allocated to insulin therapy in two different schedules: (a) after a 12-week period with enhanced compliance to diet and oral therapy: or (b) as soon as secondary failure was established. Patients were referred to a diabetologist to start insulin therapy and were referred back to their general practitioner (GP) as soon as glycaemic control was stable. We assessed fasting blood glucose, HbA1c functional health, and quality of life (Sickness Impact Profile, COOP/WONCA charts, Diabetes Symptom Checklist) at baseline, after the patient was referred back to the GP, and nine months later.. Of the 38 included patients, three patients dropped out and seven patients were not switched over to insulin therapy. In patients starting insulin therapy, mean HbA1c and fasting blood glucose level decreased from 9.5% to 7.6%, and from 12.0 mmol to 8.4 mmol, respectively (P < 0.001). The better control was accompanied by a decrease in hyperglycaemic complaints (P = 0.01). No increase in hypoglycaemic complaints was found. There were no statistically significant changes in quality-of-life parameters. After 12 weeks, patients directly referred to insulin therapy showed a statistically significant improvement in HbA1c and fasting glucose level, in contrast to patients with enhanced compliance. Quality-of-life scores did not significantly differ statistically.. Insulin therapy in poorly controlled type 2 diabetic patients from general practice resulted in a significant clinical improvement of glycaemic control, accompanied by a reduction of hyperglycaemic complaints, without an increase in hypoglycaemic complaints or an adverse influence on quality of life.

Topics: Aged; Blood Glucose; Cholesterol, HDL; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin, Isophane; Male; Middle Aged; Patient Compliance; Quality of Life; Statistics, Nonparametric; Triglycerides

We have evaluated the local tolerance and the metabolic efficacy of a lyophilized nasal insulin preparation in 10 severely hyperglycaemic Type 2 diabetic patients.. The study included two 4-month randomized periods: (A) three preprandial doses of nasal insulin secondarily combined with one evening subcutaneous NPH if the desired glycaemic control was not achieved; (B) two NPH injections daily. We assessed: (i) diabetes control on monthly HbA1c levels and occurrence of hypoglycaemic events; (ii) local tolerance on clinical symptoms, rhinoscopy, nasal muco-ciliary clearance and nasal biopsies; (iii) insulin absorption at months 0 and 4.. One patient was withdrawn because of cough and dizziness after each nasal application. HbA1c was not significantly different at month 4 (9.4 +/- 0.5% vs. 8.8 +/- 0.2%, A vs. B). Blood glucose control remained only fair in the majority of our patients. Nasal insulin was able to replace the daytime fraction of the subcutaneous insulin with a 18% efficacy. Side-effects included transient nasal hyperactivity (pruritus, sneezing and rhinorrhoea) and chronic persistence of nasal crusts. Plasma insulin profiles were not significantly different between months 0 and 4.. The utilization of nasal insulin (with or without NPH) was associated with similar diabetes control compared with NPH twice daily. Nasal insulin alone was able to achieve an adequate glycaemic control in three of the 10 patients.

Topics: Administration, Intranasal; Adult; Aged; Cross-Over Studies; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin, Isophane; Middle Aged; Patient Selection; Treatment Failure

Available basal insulin formulations do not provide a constant and reliable 24-h insulin supply. We compared the efficacy and safety of glargine (a long-acting insulin analog) and NPH insulins in insulin-naive type 2 diabetic patients treated with oral antidiabetic agents.. There were 426 type 2 diabetic patients (age 59 +/- 9 years, BMI 28.9 +/- 4.3 kg/m2, mean +/- SD) with poor glycemic control on oral antidiabetic agents randomized to treatment for 1 year with bedtime insulin glargine or bedtime NPH insulin. Oral agents were continued unchanged. The fasting blood glucose (FBG) target was 6.7 mmol/l (120 mg/dl).. Average glycemic control improved similarly with both insulins (HbA(1c), [reference range <6.5%] 8.3 +/- 0.1 vs. 8.2 +/- 0.1% at 1 year, glargine vs. NPH, mean +/- SEM, P < 0.001 vs. baseline for both). However, there was less nocturnal hypoglycemia (9.9 vs. 24.0% of all patients, glargine vs. NPH, P < 0.001) and lower post-dinner glucose concentrations (9.9 +/- 0.2 vs. 10.7 +/- 0.3 mmol/l, P < 0.02) with insulin glargine than with NPH. Insulin doses and weight gain were comparable. In patients reaching target FBG, HbA(1c) averaged 7.7 and 7.6% in the glargine and NPH groups at 1 year.. Use of insulin glargine compared with NPH is associated with less nocturnal hypoglycemia and lower post-dinner glucose levels. These data are consistent with peakless and longer duration of action of insulin glargine compared with NPH. Achievement of acceptable average glucose control requires titration of the insulin dose to an FBG target < or =6.7 mmol/l. These data support use of insulin glargine instead of NPH in insulin combination regimens in type 2 diabetes.

Topics: Adult; Aged; Blood Glucose; Blood Pressure; C-Peptide; Cholesterol; Cholesterol, HDL; Circadian Rhythm; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Antibodies; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Postprandial Period; Triglycerides

To compare the overall efficacy of combination therapies focused on fasting or postprandial blood glucose in patients with type 2 diabetes not adequately controlled with oral sulfonylurea agents alone.. A total of 135 patients were randomly assigned for 3 months to 1 of 3 combination regimens with glyburide (G) that addressed postprandial blood glucose with insulin lispro (L+G), premeal blood glucose with metformin (M+G), or fasting blood glucose (FBG) with bedtime NPH insulin (NPH+G).. At end point, HbA1c was significantly lower with all therapies (P = 0.001) and was significantly lower for L+G (7.68+/-0.88%) compared with either NPH+G (8.51+/-1.38%, P = 0.003) or M+G (8.31+/-1.31%, P = 0.025). FBG at end point was significantly lower for NPH+G (8.49+/-2.36 mmol/l) compared with either L+G (10.57+/-1.97 mmol/l, P = 0.001) or M+G (9.69+/-2.89 mmol/l, P = 0.029). The mean 2-h postprandial glucose after a test meal was significantly lower for L+G (10.87+/-2.88 mmol/l) versus NPH+G (12.21+/-3.12 mmol/, P = 0.052) or versus M+G (12.72+/-3.26 mmol/l, P = 0.009). The overall rate of hypoglycemia (episodes per 30 days) was low and not statistically significant between groups (P = 0.156).. Adding a second antihyperglycemic agent, regardless of its timing of action, lowers HbA1c and glucose values. However, when insulin lispro was used to focus on postprandial blood glucose, there was a greater impact on overall metabolic control. These data support the importance of lowering postprandial blood glucose to optimize overall glycemic control and thus improve long-term outcomes.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Fasting; Female; Glyburide; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Male; Middle Aged; Postprandial Period

To directly compare the rate of hypoglycemia and metabolic control achieved on once-daily ultralente insulin administration with twice-daily NPH insulin administration in patients with type 2 diabetes. Patient treatment satisfaction and quality of life were also examined before and during each treatment.. A crossover study was performed involving five centers and 79 patients with type 2 diabetes (fasting blood glucose > 8 mmol/l) with a 2-month run-in followed by two 6-month periods of either NPH or ultralente insulin administration. Patients were managed by a specialist nurse using a dosage adjustment protocol.. HbA1c was lower with NPH insulin therapy during each of the 6-month periods (9.7 +/- 0.2 vs. 9.1 +/- 0.3 and 9.8 +/- 0.2 vs. 9.0 +/- 0.3 mmol/l; both P < 0.01). The difference was accounted for by higher evening glucose levels with ultralente insulin (fasting 8.2 +/- 0.3 vs. 8.2 +/- 0.3 mmol/l, 6:00 P.M. 11.5 +/- 0.4 vs. 10.6 +/- 0.4 mmol/l). Despite worse control, the total number of hypoglycemic episodes was greater with ultralente insulin (220 vs. 171), and hypoglycemic episodes requiring third-party assistance occurred almost entirely with ultralente (14 vs. 1). Treatment satisfaction scores increased more with NPH insulin compared with ultralente and rose further upon changing to NPH insulin, but fell upon changing to ultralente insulin. These changes were highly significant (P < 0.001). Diabetes quality of life improved on both regimens.. These data clearly demonstrate the lower hypoglycemia rate, better glucose control, and greater treatment satisfaction accompanying therapy for type 2 diabetes with twice daily NPH compared with once daily ultralente insulin.

Topics: Blood Glucose; Blood Pressure; Body Weight; Circadian Rhythm; Comorbidity; Cross-Over Studies; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged

Insulin Mix25 is a new premixed insulin analog containing 25% insulin lispro and 75% neutral protamine lispro (NPL) suspension (NPL insulin). The aim of the study was to compare serum glucose and insulin responses after breakfast in type 2 diabetic patients who received Mix25, premixed regular/NPH (30%/70%), or NPH insulin before the meal.. We studied 22 type 2 diabetic patients of age 62 +/- 1 years, BMI 30 +/- 1 kg/m2, duration of diabetes 15 +/- 2 years, duration of insulin therapy 6 +/- 1 years, insulin dose 65 +/- 6 U/day, and HbA1c 7.9 +/- 0.2%. Ten healthy individuals (age 56 +/- 1 years, BMI 28 +/- 1 kg/m2) served as control subjects. Each patient (except healthy subjects, who were studied once each) was studied three times in a double-blind, randomized fashion. After an overnight fast, the patients received 36 +/- 4 U of test insulin. Ten minutes after insulin injection, the patients ingested a breakfast meal (512 kcal, 60% carbohydrate, 20% fat, and 20% protein), identical in all studies. Blood samples were taken before and at 10- to 30-min intervals for 240 min after the breakfast meal.. The peak rise in serum glucose was lower after Mix25 (76 +/- 7 mg/dl) than after 30/70 (94 +/- 5 mg/dl, P < 0.05) or NPH (113 +/- 4 mg/dl, P < 0.005) insulin. The incremental area under the serum glucose curve was 36% smaller after Mix25 than after 30/70 (P < 0.01) and 56% smaller than after NPH (P < 0.005) insulin. The peak rise in serum insulin concentration was higher after Mix25 (103 +/- 18 mU/l) than after 30/70 (87 +/- 13 mU/l, P < 0.05) or NPH (62 +/- 12 mU/l, P < 0.01) insulin. The incremental area under the serum insulin curve was higher after Mix25 than after 30/70 during the first 2-3 h (P < 0.02), but the difference disappeared by the end of the 4-h follow-up period. After Mix25 injection, there was an inverse correlation between the glucose response to a meal and insulin dose (r = -0.56, P < 0.01) or the incremental area under the serum insulin curve (r = -0.39, P < 0.05). No such correlations were observed with the other insulins.. Because of its faster initial absorption rate, the new premixed insulin analog Mix25 reduces blood glucose response to a breakfast meal in type 2 diabetic patients compared with premixed 30/70 (regular/NPH) or NPH insulin.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Double-Blind Method; Eating; Fasting; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Male; Middle Aged; Osmolar Concentration; Reference Values

To evaluate the efficacy of acarbose in the treatment of secondary failures to sulphonylurea-metformin therapy, its comparison against bedtime NPH insulin, and to measure the changes in postprandial metabolism resulting from both treatments.. One hundred type 2 diabetic patients in a secondary failure were included. The study begun with a run-in diet period of 6 weeks, in which an isocaloric diet was prescribed. Only subjects who continued hyperglycaemic were randomly assigned to placebo and acarbose (n = 17) or bedtime NPH insulin (n = 12). Acarbose (300 mg/day) or placebo were administered using a randomized, double blind, crossover design. Treatment periods of 3 months were separated by a 3-week washout period. Insulin was administered during 3 months. At the beginning and the end of each treatment period, an i.v. glucose tolerance test and a meal test were performed. Safety tests were done every 4 weeks.. Acarbose resulted in a small but significant improvement in fasting plasma glucose (13.5 +/- 2.4 vs. 11.3 +/- 3.9 mmol/l, p = 0.05), HbA1c (11.1 +/- 3.4 vs. 10.3 +/- 2.5%, P = 0.3) and in a decreased plasma glucose during the meal test. Bedtime insulin significantly decreased fasting plasma glucose (13.1 +/- 2.9 vs. 8.2 +/- 2.3 mmol/l, p < 0.01), HbA1c (11.7 +/- 2.9 vs. 9.4 +/- 2.7%, p < 0.01) and plasma cholesterol. No change in insulin secretion resulted from insulin and acarbose treatment.. Acarbose decreases blood glucose in secondary failure to sulphonylurea-metformin therapy; however, the decrease is not enough to reach the desired metabolic control. Bedtime NPH insulin is, by far, a more effective alternative.

Topics: Acarbose; Blood Glucose; Circadian Rhythm; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hypoglycemic Agents; Insulin, Isophane; Male; Metformin; Middle Aged; Postprandial Period; Retreatment; Sulfonylurea Compounds; Treatment Failure

The aim of this study was to compare the metabolic effects of a combination of daytime glibenclamide and evening NPH insulin with intensive insulin treatment (rapid acting insulin before meals and NPH insulin at bedtime) in patients exhibiting secondary failure to sulphonylurea treatment. Thirty-nine mildly obese NIDDM patients (BMI 25.6 +/- 0.5) were randomized after 6 weeks of intensive insulin treatment to either a combination treatment (CT, n = 20) or continued intensive insulin treatment (IT, n = 19). There were no differences between the two groups in age, diabetes duration, BMI, HbA1c, or basal and glucagon stimulated C-peptide. The patients were followed for 1 year and the findings were analysed on an intent to treat basis. Two patients in the CT group were excluded after 2 and 6 months, respectively, due to unacceptably high postprandial glucose values. There was a significant difference in HbA1c between the CT and IT groups at 6 months (8.2 +/- 0.2, n = 19, vs 6.8 +/- 0.4%, n = 19, p < 0.001)), but not at 12 months (7.8 +/- 0.3, n = 18, vs 7.5 +/- 0.4%, n = 19). After the initial intensive insulin treatment, BMI was constant in the CT group but increased significantly at 6 and 12 months in the IT group. We conclude that both treatments are associated with a marked and long-term improvement of glycaemic control. The intensive insulin treatment leads to a more pronounced weight increase which in the long run might have negative effect on overall metabolic control. Therefore, the combination treatment together with intensified education and dietary advice should be regarded as the initial treatment of choice for oral agent failure in moderately obese NIDDM patients.

Topics: Aged; Albuminuria; Analysis of Variance; Blood Glucose; Body Mass Index; C-Peptide; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glyburide; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin, Isophane; Insulin, Regular, Pork; Male; Metformin; Middle Aged; Sulfonylurea Compounds; Treatment Failure; Triglycerides

The treatment of NIDDM patients with secondary failure to sulfonylureas is still a debated problem. In this study we compared in NIDDM patients with secondary failure to glyburide, the effect of adding a single, low-dose bed time either NPH or ultralent insulin injection (0.15-0.2 U/kg) to the previously ineffective sulfonylurea treatment. Both NPH and ultralent insulin therapy have been demonstrated to be effective in ameliorating metabolic control in NIDDM patients with secondary failure to sulfonylureas. However, the addition of bed-time ultralent insulin caused a greater and significant decrease in post prandial plasma glucose. In contrast, the average fasting plasma glucose decrease was significantly greater after NPH insulin administration. These results indicate that in NIDDM patients with secondary failure to glyburide bed-time ultralent insulin administration is a better tool to improve the post prandial plasma glucose.

Topics: Blood Glucose; C-Peptide; Cross-Over Studies; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Drug Tolerance; Eating; Fasting; Female; Glyburide; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome

To examine the safety and overall clinical effects of normalizing the fasting plasma glucose (FPG) level with bedtime NPH insulin alone in patients with non-insulin-dependent diabetes mellitus (NIDDM) that is poorly controlled with maximal doses of sulfonylureas.. Twelve obese male NIDDM subjects were treated for 16 weeks with bedtime insulin after a 4-week sulfonylurea washout. The insulin dosage was increased until the FPG level was normalized. The 24-h plasma glucose profiles and lipid and HbA1c levels were measured at the beginning and end of the study, and the incidence and severity of hypoglycemic episodes were closely monitored. In addition, hyperglycemic clamp studies were performed to assess insulin secretion and provide an indirect measurement of insulin sensitivity.. FPG (14.6 +/- 0.9 mmol/l at week 0) was normalized ( < 6.4 mmol/l) within 6 weeks (5.9 +/- 0.6 mmol/l) and remained at target levels until the end of the study (4.0 +/- 0.03 mmol/l at week 16, P < 0.001). The insulin dose was 80 +/- 9 U/day (0.86 +/- 0.10 U/kg). Improved glycemic control was confirmed by a reduction in HbA1c (10.9 +/- 0.05 vs. 7.2 +/- 0.2%, P < 0.001) and mean 24-h glucose (17.2 +/- 0.2 vs. 7.4 +/- 0.2 mmol/l, P < 0.001). The incidence of mild or moderate hypoglycemic episodes was 3.4 +/- 1/patient for the entire 16-week study, and no patient experienced severe hypoglycemia. Bedtime insulin significantly improved total cholesterol, low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, and triglyceride levels (P < 0.01). Weight gain was 2.4 +/- 0.7 kg, and blood pressure was unchanged. During the hyperglycemic clamp, there was an improvement in the first phase (P < 0.001) and in the second phase (P < 0.01) of insulin secretion. There also was an increase in the rate of exogenous glucose infused (M) (P < 0.01) and in the M/C-peptide ratio (P < 0.02), suggesting enhanced insulin sensitivity.. NPH insulin given at bedtime in amounts sufficient to achieve a normal FPG level does not cause excessive or severe hypoglycemia and does lead to good glycemic and lipid control in NIDDM. Bedtime insulin therapy also is accompanied by improved insulin secretion and insulin sensitivity. We conclude that a single dose of insulin alone at bedtime merits consideration as a therapeutic strategy in patients with poorly controlled NIDDM.

Topics: Analysis of Variance; Blood Glucose; Blood Pressure; Body Mass Index; Body Weight; C-Peptide; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cholesterol, VLDL; Diabetes Mellitus; Diabetes Mellitus, Type 2; Drug Administration Schedule; Fasting; Glucose; Glycated Hemoglobin; Humans; Insulin, Isophane; Liver; Male; Middle Aged; Obesity; Reference Values; Time Factors; Triglycerides

To compare the effect of bedtime NPH insulin or preprandial regular insulin combined with glibenclamide on metabolic control in non-insulin-dependent diabetes mellitus (NIDDM) patients with secondary failure to sulfonylurea therapy.. Eighty NIDDM patients were randomized to treatment with either three preprandial doses of regular insulin (daytime group D) or a bedtime dose of NPH insulin (nocturnal insulinization, group N), both regimens being combined with 10.5 mg of glibenclamide. Metabolic profiles were obtained at 0, 6, 16 weeks.. Glycemic control had improved significantly in both groups after 4 months. Fasting blood glucose was significantly lower compared with baseline in both groups. The mean change +/- SD in group D was -2.8 +/- 3.5 mmol/l and in group N -6.4 +/- 3.0 mmol/L, the reduction being more pronounced in group N compared with group D (P < 0.0001). HbA1c was lowered similarly, from 9.2 +/- 1.4 to 7.1 +/- 1.2% in group D (P < 0.0001) and from 9.1 to 1.1 to 7.5 +/- 1.5% in group N (P < 0.0001). The total daily insulin doses were similar, 29 +/- 11 U in group D and 26 +/- 9 U in group N, and the circulating insulin levels during daytime were higher in group D than in group N. Total serum cholesterol and triglycerides were similarly and significantly lowered compared with baseline in both groups. Weight gain was more pronounced in group D (3.4 +/- 0.3 kg) than in group N (1.9 +/- 1.9 kg; D vs. N, P < 0.002), and the change was inversely correlated with initial eight but not with the improvement in HbA1c.. The two insulin regimens exert similar effect on glucose metabolism and serum lipids in NIDDM patients on combination therapy. Weight gain is more pronounced in patients given insulin during the daytime when preprandial doses of short-acting insulin are used.

Topics: Adult; Aged; Blood Glucose; Body Weight; C-Peptide; Cholesterol; Cholesterol, HDL; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Eating; Glyburide; Humans; Hypoglycemic Agents; Insulin; Insulin, Isophane; Middle Aged; Time Factors; Treatment Failure; Triglycerides

It was the aim of this study to determine whether FFA inhibit insulin-stimulated whole body glucose uptake and utilization in patients with non-insulin-dependent diabetes. We performed five types of isoglycemic (approximately 11mM) clamps: (a) with insulin; (b) with insulin plus fat/heparin; (c) with insulin plus glycerol; (d) with saline; (e) with saline plus fat/heparin and two types of euglycemic (approximately 5mM) clamps: (a) with insulin; (b) with insulin plus fat/heparin. During these studies, we determined rates of glucose uptake, glycolysis (both with 3[3H] glucose), glycogen synthesis (determined as glucose uptake minus glycolysis), carbohydrate oxidation (by indirect calorimetry) and nonoxidative glycolysis (determined as glycolysis minus carbohydrate oxidation). Fat/heparin infusion did not affect basal glucose uptake, but inhibited total stimulated (insulin stimulated plus basal) glucose uptake by 40-50% in isoglycemic and in euglycemic patients at plasma FFA concentration of approximately 950 and approximately 550 microM, respectively. In isoglycemic patients, the 40-50% inhibition of total stimulated glucose uptake was due to near complete inhibition of the insulin-stimulated part of glucose uptake. Proportional inhibition of glucose uptake, glycogen synthesis, and glycolysis suggested a major FFA-mediated defect involving glucose transport and/or phosphorylation. In summary, fat produced proportional inhibitions of insulin-stimulated glucose uptake and of intracellular glucose utilization. We conclude, that physiologically elevated levels of FFa could potentially be responsible for a large part of the peripheral insulin resistance in patients with non-insulin-dependent diabetes mellitus.

Topics: Aged; Analysis of Variance; Blood Glucose; Diabetes Mellitus, Type 2; Emulsions; Fat Emulsions, Intravenous; Fatty Acids, Nonesterified; Female; Glucagon; Glucose; Glucose Clamp Technique; Heparin; Humans; Infusions, Intravenous; Insulin, Isophane; Male; Middle Aged; Phospholipids; Recombinant Proteins; Safflower Oil; Soybean Oil

A randomized prospective study was conducted to determine whether the insulin regimen for NIDDM subjects poorly controlled on oral therapy should be designed primarily to control basal metabolism or to control mealtime hyperglycaemia. Grossly obese subjects were excluded. After a 2-month run-in phase involving intensive education, subjects were randomized to therapy with twice daily isophane or three times daily soluble insulin. Both Protaphane and Actrapid brought about similar improvement in HbA1 (9.5 +/- 0.5 and 9.7 +/- 0.4%) compared with baseline (11.7 +/- 0.5%; p < 0.001). Diurnal blood glucose profiles showed that despite the good post-prandial control achieved by pre-meal soluble insulin, loss of control occurred overnight, resulting in higher fasting blood glucose levels compared with Protaphane therapy (8.0 +/- 0.8 vs 10.6 +/- 0.8 mmol l-1; p < 0.05). The overall rate of hypoglycaemia was 0.44 patient-1 year-1. Thirty-two mild hypoglycaemic episodes occurred on Protaphane therapy and 79 on Actrapid therapy. Using formal psychometric tests it was shown that insulin therapy was associated with improved treatment satisfaction and that this was greater on Protaphane therapy (p < 0.05). Overall well-being increased similarly in the two groups. All subjects wished to continue with insulin therapy after the conclusion of the study. The insulin regimen for moderately or poorly controlled non-insulin-dependent diabetes should primarily be designed to correct the basal insulin deficiency rather than to mimic normal meal-induced insulin secretion.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Cholesterol; Circadian Rhythm; Cross-Over Studies; Diabetes Mellitus, Type 2; Drug Administration Schedule; Eating; Glycated Hemoglobin; Humans; Insulin; Insulin, Isophane; Insulin, Regular, Pork; Middle Aged; Patient Education as Topic; Patient Satisfaction; Prospective Studies; Quality of Life; Surveys and Questionnaires; Triglycerides; Weight Gain

The aim of this study was to assess the immunocompetence of T cells from patients with poorly controlled diabetes with respect to Candida albicans antigen and to compare the relative immunogenicity of human insulin, bovine insulin and protamine at the T-cell level during 6 months treatment with human or bovine NPH insulins. T-cell proliferation was measured in vitro in response to C. albicans, bovine and human insulin, bovine and human NPH and protamine in 17 patients with newly-diagnosed type 1 (insulin-dependent) and 12 with poorly-controlled type 2 (non-insulin-dependent diabetes) before and after 0.5, 1, 3 and 6 months of treatment with either bovine or human NPH insulin. The following results were found: Baseline responses to C. albicans (as a recall antigen) were similar for patients and controls despite marked hyperglycaemia in the patients. No patient had a response greater than mean + 2 S.D. of controls to human or bovine insulin before starting treatment, or had insulin autoantibodies. Treatment with human NPH insulin did not induce T-cell responses to human or bovine insulin, but 3/13 (23%) patients treated with bovine NPH responded to bovine and human insulin after 6 months, of whom one responded exclusively to human. In contrast, 6 (46%) bovine and 3 (19%) human NPH-treated patients responded to protamine. It was concluded that there is no evidence of T-cell immunosuppression in poorly-controlled diabetes or of T-cell autoimmunity to insulin in newly-diagnosed type 1 diabetes. Treatment with bovine NPH insulin immunizes T cells to insulin, but human NPH does not.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Animals; Antigens, Fungal; Autoantibodies; Candida albicans; Cattle; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; HLA-DR Antigens; Humans; Immunophenotyping; Insulin, Isophane; Islets of Langerhans; Lymphocyte Activation; Middle Aged; Protamines; Recombinant Proteins; T-Lymphocytes

Morning versus bedtime administration of NPH insulin was compared in 12 subjects with Type 2 diabetes and overt fasting hyperglycaemia. Subjects were studied at baseline (diet alone) and after 2 months on each of the two insulin programmes in a random crossover design, in which dosage was increased until at least one daily preprandial blood glucose was consistently in the range of 3.9 to 6.0 mmol l-1. Mean (+/- SEM) daily total insulin dosage was equivalent for the morning (0.36 +/- 0.03 units kg-1) and for the bedtime (0.37 +/- 0.03 units kg-1) insulin administration schedules. Glycaemic control was improved on both insulin regimens, but was better on bedtime than morning insulin. Fasting plasma glucose (mmol l-1) was 12.0 +/- 0.7 (baseline), 8.6 +/- 0.7 (morning), and 4.6 +/- 0.3 (bedtime), respectively. Mean 24 h plasma glucose (mmol l-1) was 13.3 +/- 1.3, 9.0 +/- 0.7, and 7.8 +/- 0.7. Glycated haemoglobin (%) was 7.65 +/- 0.35, 6.23 +/- 0.26, and 5.81 +/- 0.32. The improvement of basal glycaemia is a consequence of increased basal metabolic clearance of glucose (baseline, 47.6 +/- 3.1 ml m-2 min-1; morning 63.5 +/- 5.4, bedtime 103.5 +/- 7.1). There was no change in hepatic glucose output. It is concluded that bedtime administration of intermediate acting insulin results in increased basal insulinaemia, leading to improved basal glycaemia and consequent improved overall metabolic control, compared to morning insulin administration. Therefore, bedtime may be the preferable timing of insulin therapy for patients with Type 2 diabetes and overt fasting hyperglycaemia.

Topics: Circadian Rhythm; Diabetes Mellitus, Type 2; Drug Administration Schedule; Fasting; Female; Humans; Hyperglycemia; Insulin, Isophane; Male; Middle Aged; Time Factors

To compare the effectiveness of alternative combined treatments in patients with non-insulin-dependent diabetes mellitus (NIDDM) with secondary failure to sulfonylureas.. A crossover study was carried out by randomly assigning 16 NIDDM patients to a combined treatment with the addition of either a single low-dose bedtime injection of 0.2 U/kg body wt NPH insulin or an oral three times a day administration of 1.5 g/day metformin to the previously ineffective glyburide treatment.. Both combined therapies significantly (P less than 0.01) reduced fasting plasma glucose (FPG), postprandial plasma glucose (PPPG) and percentage of HbA1. The addition of metformin was more effective than the addition of insulin (P less than 0.01) in improving PPPG in the 8 patients with higher post-glucagon C-peptide levels. In contrast, the efficacy of neither combined therapy was related to patient age, age of diabetes onset, duration of the disease, percentage of ideal body weight, and FPG. The addition of insulin but not metformin caused a significant (P less than 0.01) increase of mean body weight. Neither combined treatment caused changes in serum cholesterol and triglyceride levels. No symptomatic hypoglycemic episode was reported in any of the 16 patients.. The addition of bedtime NPH insulin or metformin was effective in improving the glycemic control in most NIDDM patients with secondary failure to glyburide. The combination of metformin and sulfonylurea was more effective in reducing PPPG and did not induce any increase of body weight.

Topics: Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Eating; Fasting; Glyburide; Glycated Hemoglobin; Humans; Insulin, Isophane; Metformin; Middle Aged; Obesity

Topics: Cross Reactions; Diabetes Mellitus, Type 2; Glyburide; Humans; Immunoassay; Insulin; Insulin, Isophane; Proinsulin; Reference Values

To compare the effect of morning and bedtime NPH insulin combined with daytime sulfonylurea on glycemic control in non-insulin-dependent diabetes mellitus (NIDDM) patients no longer responding to treatment with sulfonylureas alone.. Twenty-four NIDDM patients who fulfilled these criteria were randomized to treatment with Protaphan human insulin in the morning or at bedtime (22 +/- 1 IU) plus 3.5 mg glibenclamide twice a day.. Morning and bedtime NPH insulin resulted in equal reduction of HbA1 (from 13.5 +/- 0.3 to 9.4 +/- 0.1 and 9.6 +/- 0.2%, respectively) and mean self-monitored blood glucose (9.2 +/- 0.5 vs. 10.1 +/- 0.4 mM). Bedtime insulin resulted in lower morning blood glucose (7.8 +/- 0.5 vs. 9.1 +/- 0.4 mM; P less than 0.01), whereas morning insulin resulted in lower evening blood glucose (10.1 +/- 0.6 vs 12.1 +/- 0.6 mM, P less than 0.01).. Morning and bedtime NPH insulin combined with glibenclamide are equipotent in the treatment of NIDDM patients with secondary failure to sulfonylurea. However, this treatment regimen normalizes blood glucose only in a small group of patients. Therefore, more intensified insulin therapy seems to be required to achieve this goal.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glyburide; Humans; Insulin, Isophane; Male; Middle Aged; Multivariate Analysis; Random Allocation; Time Factors

Treatment with neutral protamine Hagedorn (NPH) insulin predisposes individuals with diabetes to anaphylactoid reactions when given bolus protamine for heparin reversal during cardiovascular procedures. To prospectively examine production of protamine antibodies, 30 patients with non-insulin dependent diabetes were followed for 12 months from initiation of therapy with porcine NPH or Lente insulin. Twenty-one subjects were randomly assigned to NPH (protamine containing) and nine controls to Lente (protamine free) insulin. Protamine specific IgG antibody was produced by 6/21 (29%) of NPH-treated subjects and 0/9 controls. Among NPH treated subjects, there was no difference between protamine antibody producers and non-producers with regard to age, race, weight, or pre-treatment glycosylated hemoglobin. Both producer and non-producer groups received similar amounts of insulin and protamine and achieved similar glycemic control. Insulin antibodies were made by 4/6 (67%) of protamine antibody producers and by 6/15 (40%) of non-producers (NS). The authors conclude that one of three new diabetics who are treated with porcine NPH insulin will make IgG protamine antibodies. These antibodies do not affect insulin requirements, glycemic control, or insulin antibody production. Because of the frequency of protamine antibody production and the risk of anaphylaxis to bolus protamine administration in NPH treated diabetics, the authors suggest that NPH insulin-treated individuals should avoid heparin reversal by protamine.

Topics: Diabetes Mellitus, Type 2; Enzyme-Linked Immunosorbent Assay; Glycated Hemoglobin; Histocompatibility Testing; HLA Antigens; Humans; Immunoglobulin G; Insulin, Isophane; Insulin, Long-Acting; Prospective Studies; Protamines; Random Allocation

In Switzerland it is still a debatable point whether diabetics whose treatment has been changed from animal to human insulin notice premonitory symptoms of hypoglycemia to a lesser degree and whether this could be hazardous for them. In a prospective study, 18 longstanding type 1 and type 2 diabetics, treated with insulin Lente MC, were selected and observed at frequent intervals for three months. This first period was followed by a transfer to human insulin (Protaphan HM) and a close observation for another three months. Before the transfer, all patients were well informed about a possible change in premonitory symptoms of hypoglycemia. The initial dose of Protaphan HM was 10% lower than in the treatment with Lente MC. During the three month period with human insulin, we observed no change with regard to blood-sugar regulation or Hb-A1. The most important observation was that the number of hypoglycemic episodes did not change after the transfer to human insulin. There were only mild to moderate degrees of hypoglycemia, the average being three episodes per patient. The change to human insulin was without any problems for the patients: they all preferred to stay on Protaphan HM for future treatment. Also, in general practice, patients can be changed without difficulties from animal to human insulin, provided that the above-mentioned precautions are respected.

Topics: Adult; Aged; Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged

Due to a longer plasma half-life and half-time of action on glucose metabolism biosynthetic human proinsulin was thought to be an alternative to long-acting insulin preparations. To test this hypothesis we studied 23 type 2 diabetic patients who could no longer be treated sufficiently with oral hypoglycaemic agents. After an initial 1 week phase during which all patients received protamine bound insulin twice daily, the patients either continued on NPH insulin (Group A, n = 11) or were randomly switched to human proinsulin (Group B, n = 12). Glucose profiles and peripheral and hepatic insulin sensitivity (euglycaemic clamp: 120 mU m-2 min-1) were measured at the end of the initial period (Time 1) and 1 week later (Time 2). The insulin-mediated glucose disposal (RD) was not changed after either treatment (group A: 176 +/- 18 vs. 192 +/- 19 mg m-2 min-1; group B: 175 +/- 15 vs. 174 +/- 12 mg m-2 min-1 for times 1 and 2, respectively, NS). Suppression of hepatic glucose output (HGO) was complete in both groups at both times. Fasting blood glucose levels (FBG) and basal HGO were equally low at times 1 and 2 (group A: FBG 118 vs. 123 mg dl-1, BHGO 81 vs. 79 mg m-2 min-1; group B: FBG 118 vs. 106 mg dl-1, BHGO 87 vs. 84 mg m-2 min-1; NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glucose; Half-Life; Humans; Insulin Resistance; Insulin, Isophane; Liver; Male; Proinsulin; Randomized Controlled Trials as Topic

To compare the relative efficacy, risks, and benefits of insulin with glyburide in achieving normoglycemia in non-insulin-dependent diabetes mellitus.. Randomized, double-blind, placebo-controlled trial with a 9-month treatment period.. University hospital.. Thirty-one patients with non-insulin-dependent diabetes mellitus who did not have normal glucose control with diet alone.. Once-per-day NPH insulin and placebo glyburide, or glyburide and once-per-day placebo insulin injection. Active drug and placebo adjusted in parallel to achieve fasting plasma glucose level less than 6.4 mmol/L (115 mg/dL) without hypoglycemia.. Insulin and glyburide produced similar improvement in fasting blood glucose levels and hemoglobin A1c concentrations, similar frequencies of mild symptomatic hypoglycemia, and similar weight gain despite dietary reinforcement. Triglyceride and cholesterol levels decreased and high-density lipoprotein cholesterol and ratios of high-density lipoprotein to total cholesterol increased in both groups, with a significantly greater improvement in high-density lipoprotein cholesterol and ratio of high-density lipoprotein total cholesterol in patients treated with insulin.. Therapy with glyburide or once-per-day NPH insulin provides a similar degree of glucose control in patients with non-insulin-dependent diabetes mellitus. Insulin may have a relative advantage in that it is associated with higher levels of high-density lipoprotein cholesterol and a higher ratio of high-density lipoprotein to total cholesterol.

Topics: Blood Glucose; Body Weight; Cholesterol; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glyburide; Glycated Hemoglobin; Humans; Insulin, Isophane; Male; Middle Aged; Random Allocation; Triglycerides

Although intraindividual comparisons of commonly used human standard combination insulins have not been made, pharmacodynamic differences between preparations in the by now no vast insulin market have been highlighted. The action of five bio- or semisynthetic human insulins of all four manufacturers using the same galenic formula and with a fixed normal insulin content of 20-30% was tested at equal dosages in type IIa and type IIb diabetics with differing residual pancreatic secretion. No differences were demonstrated in onset, maximum or duration of action. The blood-sugar lowering effect of the preparations is particularly marked in the late morning hours and may, if not counteracted by adequate carbohydrate intake, lead to hypoglycaemia. Duration of action of the preparations depends on the individual extent of endogenous pancreatic insulin reserves.

Topics: Clinical Trials as Topic; Diabetes Mellitus, Type 2; Drug Combinations; Female; Humans; Insulin; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Random Allocation; Recombinant Proteins

Insulin requirements, C-peptide levels, and serum lipids have been assessed in 12 obese, insulin-requiring (greater than 60 U/day) patients with type II diabetes mellitus, in a randomized crossover fashion with two treatment regimens: NPH alone and combined NPH and tolazamide, over a period of 3 months each, with maintenance of weight and glycemic control (HgA1, 2hpp and mean 24h glucose profile) at comparable levels. Serum cholesterol improved in both groups compared to their respective baseline values (p less than 0.05). In addition, serum triglyceride was lower (p less than 0.05) in the combined therapy as compared with NPH alone therapy. Insulin requirements were decreased by 23% (p less than 0.002) in the combined therapy group, without significant change in weight, glycemic control, or C-peptide levels. However, C-peptide increments in the combined therapy group were significantly higher than the baseline by 70% (p less than 0.02). NPH plus tolazamide therapy as compared with NPH alone lowers insulin requirement in obese, type II diabetic women without significant alteration in glycemic control, possibly by an increased tissue sensitivity to insulin, and decreases serum triglyceride levels.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Cholesterol; Diabetes Mellitus; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Humans; Insulin, Isophane; Middle Aged; Obesity; Prospective Studies; Random Allocation; Tolazamide; Triglycerides

Porcine and semisynthetic human insulin preparations (Nordisk) having the same content of regular insulin, same galenic characteristics and same degree of purity, were tested in type I, type IIa and type IIb diabetics. There was no difference as to the duration of action. This is contrary to some earlier reports stating that protamine-bound biosynthetic human insulin has a shorter duration of action than porcine preparations. The onset of the hypoglycaemic action in type IIa diabetics is significantly more rapid with isophane human insulin than with isophane pork insulin. The use of an insulin pump prior to testing the duration of action of intermediate insulin preparations appears to be superior to other methods.

Topics: Aged; Animals; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Insulin Infusion Systems; Insulin, Isophane; Male; Middle Aged; Swine; Time Factors

Few studies addressed the efficacy of human insulin regimens (mostly premix insulin) used in many low-and-middle income countries on glycemic control of children and adolescents with diabetes. The aim of this study was to assess the efficacy of the premix insulin on the glycated hemoglobin (HbA. A retrospective study was carried out from January 2020 to September 2022 on patients with type 1 diabetes aged below 18 years followed in Burkina Life For A Child program. They were categorized into three groups, on regular with NPH insulin (Group A), on premix insulin (Group B) and on regular with premix insulin (Group C). Outcome was analyzed based on HbA. Sixty-eight patients with a mean age of 15.38 ± 2.26 years and the sex ratio (M/W) 0.94 were studied. There were 14 in Group A, 20 in Group B, and 34 patients in Group C. The mean HbA. Our results indicate that the use of premix insulin gives a better glycemic control than NPH insulin. However, further prospective study of these insulin regimens with a strengthening education strategy and glycemic control by continuous glucose monitoring and HbA

Topics: Adolescent; Aged; Blood Glucose; Blood Glucose Self-Monitoring; Child; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin, Isophane; Prospective Studies; Retrospective Studies

To prevent hypoglycemic episodes, the management of insulin therapy against post-transplant diabetes mellitus (PTDM) is important. We compared glargine (long-acting insulin) versus NPH isophane (intermediate-acting insulin) as an armamentarium against PTDM. Indeed, the study evaluated PTDM patients with hypoglycemic episodes treated with isophane or glargine.. We evaluated a total number of 231 living-donor renal transplant recipients with PTDM of age ≥ 18 years admitted to the hospital between January 2017 and September 2021. However, patients taking hypoglycemic agents before transplantation were excluded from this study. Out of 231 patients, 52 (22.15%) suffered from PTDM out of whom 26 were treated with glargine or isophane.. After applying exclusion criteria, out of 52 PTDM patients 23 were included in the study: 13 PTDM patients were treated with glargine, whereas 10 PTDM patients with isophane. Our analysis revealed 12 episodes of hypoglycemia in glargine-treated PTDM patients compared to 3 in isophane-treated PTDM patients (p = 0.056). Clinically, 9 out of 15 hypoglycemic episodes were nocturnal (60%). Furthermore, no other risk factors were observed in our study population. Detailed analysis showed that both groups had equivalent doses of immunosuppressants and oral hypoglycemic agents. The odds ratio for hypoglycemia in the group treated with isophane compared to that treated with glargine was 0.224 (95% CI, 0.032-1.559). Glargine users recorded significantly lower blood sugar levels before lunch, dinner and at bedtime with p-values of 0.001, 0.009 and 0.001 respectively. A better hemoglobin A1c (HbA1c) level was seen in the glargine vs. isophane group (6.98 ± 0.52 vs. 7.45 ± 0.49, p-value 0.03).. The study shows better blood sugar control with long-acting insulin analog, glargine, than with intermediate-actin analog, isophane. Overall, a higher number of hypoglycemic episodes was nocturnal. Long term safety of long-acting insulin analogs needs to be further studied.

Topics: Adolescent; Blood Glucose; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

To determine whether the use of long-acting insulin analogues is associated with an increased risk of incident diabetic retinopathy (DR) among patients with type 2 diabetes.. Using data from the Clinical Practice Research Datalink Aurum, this retrospective, population-based cohort study included patients with type 2 diabetes who initiated a long-acting insulin analogue (glargine, detemir, degludec) or Neutral Protamine Hagedorn (NPH) insulin. The primary outcome was incident DR. We used Cox proportional hazards models with inverse probability of treatment weighting to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident DR with insulin analogues versus NPH insulin.. There were 66 280 new users of long-acting insulin analogues and 66 173 new users of NPH insulin. The incidence rate of DR was 101.7 per 1000 person-years (95% CI, 98.7-104.8) for insulin analogues and 93.2 (95% CI, 90.0-96.5) per 1000 person-years for NPH insulin. Compared with the current use of NPH insulin, insulin analogues were not associated with the risk of incident DR (HR 1.04, 95% CI, 0.99-1.09). The adjusted HRs were 0.84 (95% CI, 0.66-1.07) for proliferative DR and 1.02 (95% CI, 0.97-1.08) for non-proliferative DR.. Compared with NPH insulin, long-acting insulin analogues were not associated with the risk of incident DR among patients with type 2 diabetes. This finding provides important reassurance regarding the safety of long-acting insulin analogues with respect to incident DR.

Topics: Cohort Studies; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Retrospective Studies

Type 2 Diabetes Mellitus (DM2) is a public health and socioeconomic problem, generating direct medical costs for its treatment.. To analyze the cost-effectiveness of monotherapy and bitherapy treatments in patients with DM2.. Cost-effectiveness, observational, ambispective, cross-sectional and analytical analysis of files in a first level medical unit. The data in the cost matrix was executed with the Office Excel 2010 program; the most prescribed drug was identified and compared with monotherapy and bitherapy.. The annual direct medical costs of the total population were drug cost $118,561.70MN, hospitalization cost $243,756.00MN, consultation cost $327,414.00MN and clinical trial cost $2416.79MN, obtaining an annual total of $692,148.58MN. metformin was the most indicated in monotherapy (88.4%) and as standard therapy it has higher cost-effectiveness compared to glibenclamide. In bitherapy it was metformin/glibenclamide (35.7%) versus the therapeutics of metformin/NPH insulin, metformin/insulin glargine and metformin/dapagliflozin, which had a better cost-effective result, with an incremental cost effectiveness of -$1,128,428.50MN, -$34,365.00 MN, -$119,848.97MN respectively.. Metformin presented a better cost-effectiveness ratio in monotherapy, while in bitherapy it was the metformin/NPH insulin association.. La Diabetes Mellitus tipo 2 (DM2) es un problema de salud pública y socioeconómico, tanto por su alta incidencia como por la generación de los costos médicos directos para su tratamiento.. Analizar el costo-efectividad de los tratamientos en monoterapia y biterapia en pacientes con DM2.. Análisis costo-efectividad, observacional, ambispectivo, transversal y analítico. Análisis de expedientes en una unidad médica de primer nivel. Se ejecutaron los datos en la matriz de costos con el programa Office Excel 2010; se identificó el fármaco más prescrito, se comparó con monoterapia y biterapia.. Los costos médicos directos anuales del total de la población fueron: costo del medicamento $118,561.70MN, costo por hospitalización $243,756.00MN, costo por consultas $ 327,414.00MN y costo por estudios clínicos $2416.79MN, obteniendo un total anual de $692,148.58MN. La metformina fue la más indicada en monoterapia (88.4%) y como terapéutica estándar tiene mayor costo-efectividad comparada con la glibenclamida. En biterapia fue metformina/glibenclamida (35.7%) versus las terapéuticas de metformina/insulina NPH, metformina/insulina glargina y metformina/dapagliflozina, las cuales tuvieron un resultando más costo-efectivo, con un costo efectividad incremental de -$1,128,428.50MN, -$34,365.00MN, -$119,848.97MN respectivamente.. La metformina presento mejor relación costo efectividad en monoterapia, mientras que en biterapia fue la asociación metformina/Insulina NPH.

Topics: Cost-Benefit Analysis; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Glyburide; Humans; Hypoglycemic Agents; Insulin, Isophane; Metformin; Mexico

This study investigated the ethnic differences in glycaemic levels and clinical characteristics among insulin-naïve people with type 2 diabetes (T2D) initiating biphasic insulin aspart 30/70 (BIAsp 30) in primary practice in England.. Retrospective, observational cohort study utilizing data from the Clinical Practice Research Datalink Aurum database, including White, South Asian, Black and Chinese insulin-naïve adults with T2D, initiating BIAsp 30. The index date was that of the first BIAsp 30 prescription. Endpoints included change in glycated haemoglobin (HbA1c) and body mass index (BMI) 6 months post index.. In total, 11 186 eligible people were selected (9443 White, 1116 South Asian, 594 Black, 33 Chinese). HbA1c decreased across all subgroups 6 months post index: estimated %-point changes [95% CI of -2.32 (-2.36; -2.28) (White); -1.91 (-2.02; -1.80) (South Asian); -2.55 (-2.69; -2.40) (Black); and -2.64 (-3.24; -2.04) (Chinese)]. The BMI increased modestly 6 months post index in all subgroups [estimated changes (95% CI) kg/m. Among insulin-naïve people with T2D initiating BIAsp 30, clinically meaningful HbA1c reductions in all ethnicities were observed. Some ethnic groups had larger reductions than others, but differences were small. In all groups, small BMI increases were seen, with small differences observed between groups. Hypoglycaemia rates were low.

Topics: Adult; Biphasic Insulins; Cohort Studies; Diabetes Mellitus, Type 2; England; Glycated Hemoglobin; Glycemic Control; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Insulin, Regular, Human; Retrospective Studies; Treatment Outcome

The objective of this retrospective study was to compare glycemic control, pregnancy outcomes, and neonatal outcomes in women with gestational diabetes mellitus (GDM) treated with (a) insulin detemir and (b) insulin neutral protamine Hagedorn (NPH).. A total of 192 women with GDM were included in the analysis. Ninety-eight women received detemir, while 94 women received NPH. Data regarding medical history, glycemic control, and time and mode of delivery, as well as neonatal outcomes, were recorded.. Baseline characteristics were comparable between the two groups. There were no differences with respect to the week of insulin initiation, total insulin dose, duration of insulin therapy, daily insulin dose/weight in early and late pregnancy, or the number of insulin injections per day. Maternal overall weight gain during pregnancy and weight gain per week did not differ either. The detemir group had slightly lower HbA1c levels at the end of gestation [median: det 5.2% (33 mmol/mol) vs NPH 5.4% (36 mmol/mol), p=0.035). There were no cases of hypoglycemia or allergic reactions in the two groups. There were also no differences regarding neonatal outcomes according to the available data, given that data in some cases were missing.. The use of insulin detemir was found to be equally effective and safe compared to NPH in women with GDM.

Topics: Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Glycemic Control; Humans; Hypoglycemic Agents; Infant, Newborn; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Pregnancy; Pregnancy Outcome; Retrospective Studies; Weight Gain

This study examined the impact of insulin products donated by a pharmaceutical manufacturer and dispensed by Dispensary of Hope-partnered pharmacies on medication access and treatment outcomes among uninsured patients with type 2 diabetes (T2D).. This was a pilot, single-center, retrospective observational study.. Uninsured patients with diabetes who were newly established with Ascension Medical Group clinics for the treatment of T2D were included in this study. Participants were prescribed insulin glargine, insulin isophane, or insulin isophane/insulin regular insulin therapy between March 2020 and August 2021. A retrospective chart review was conducted. Information collected included participants' hemoglobin A1c (HbA1c) level at baseline, 3 months, and 6 months; change in HbA1c level; insulin prescribed; fill history; whether they had been referred to a patient assistance program; and whether they were seen by a pharmacist under a collaborative practice agreement.. Thirty-eight participants were assessed, and 22 met criteria for the primary outcome. The mean HbA1c level decreased from 11.2% at baseline to 8.9% at 3 months and 8.8% at 6 months, resulting in a mean change in HbA1c of -2.4 percentage points (P = .033). Eleven participants (50%) had an HbA1c level of less than 9% at 6 months. The mean proportion of days covered was 76%. The mean monthly savings for insulin ranged from $183.74 (insulin isophane) to $253.84 (insulin glargine) per participant.. Our results showed a significant improvement in glycemic control among participants, demonstrating the substantial impact that pharmacies partnered with charitable medication distributors such as the Dispensary of Hope can have on individuals with insulin-treated T2D.

Topics: Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Regular, Human; Medically Uninsured; Retrospective Studies

This study includes modeling and simulation of insulin aspart pharmacokinetics (PK). The authors used PK data of biosimilar insulins-insulin aspart and biphasic insulin aspart 30/70-to develop a predictive population PK model for the insulins. The model was built via Monolix software, taking into account the weight-based dosing and the dose and body-weight effects on the parameters. The model-based simulations were performed using the R package mlxR for various administered doses and various ratios of insulin aspart forms for a better understanding of the insulin behavior. The optimal model was a 1-compartment model with a combination of zero- and first-order absorptions, with absorption lag for the soluble form of insulin aspart and first-order absorption for the insulin aspart protamine suspension. The assumption of identical behavior of 2 insulins at the distribution and elimination phases was made. The developed PK model was fitted successfully to the experimental data, and all fitted parameters displayed a moderate coefficient of variation. The PK model allows us to predict PK profiles for various doses and formulations of insulin aspart and can be used to improve the accuracy, safety, and ethics of novel clinical trials of insulin.

Topics: Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Insulins

Though many trials had examined the effectiveness of taking insulin with or without oral agents, there are limited real-world data, particularly among patients with type 2 diabetes mellitus (T2DM) in the resource limited settings. This study aimed to examine level of glycemic control among patients with T2DM after initiation of insulin and factors associated with poor glycemic control.. An analysis of retrospective medical records of patients with T2DM who initiated insulin due to uncontrolled hyperglycemia by oral agents was conducted from 2015-2020 in the University of Gondar Comprehensive Specialized Hospital. Difference in median fasting plasma glucose (FPG) before and after insulin initiations was examined by a Wilcoxon signed-rank test. Kruskal Wallis test was performed to explore difference in the median level of FPG among treatment groups. A logistic regression model was also used to identify associated factors of poor glycemic control after insulin initiation. Statistical significance was declared at p < 0.05.. Of 424 enrolled patients with T2DM, 54.7% were males and the mean age was 59.3±9.3 years. A Wilcoxon signed-rank test showed that there was significant deference in FPG before and after insulin initiation (P < 0.001). A declining trend of blood glucose was observed during the 1-year follow-up period of post-initiation. However, majority of the participants did not achieve target glucose levels. Participants who had higher FPG and systolic blood pressure (SBP) before insulin initiation were found more likely to have poor glycemic control after insulin initiation. Similarly, patients who received atorvastatin compared with simvastatin were found to have poor glycemic control in the post-period of initiation (P = 0.04). Premixed insulin was associated with a lower likelihood of poor glycemic control than neutral protamine Hagedorn (NPH) insulin (P < 0.001).. Following insulin initiation, a significant change in glycemic level and declining trend of FPG was observed during a 1-year follow-up period. However, the majority of patients still had a poorly controlled glycemic level. Appropriate management focusing on predictors of glycemic control would be of a great benefit to achieve glycemic control.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Ethiopia; Female; Follow-Up Studies; Glycated Hemoglobin; Glycemic Control; Hospitals, University; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin, Isophane; Insulin, Regular, Human; Male; Middle Aged; Retrospective Studies

To compare the risk of cardiovascular outcomes associated with long-acting insulin analogues versus neutral protamine Hagedorn (NPH) insulin among patients with type 2 diabetes.. We conducted a population-based retrospective cohort study using the UK Clinical Practice Research Datalink Aurum, linked with hospitalization and vital statistics data. Patients with type 2 diabetes who initiated basal insulin treatment between 2002 and 2018 were included in the study. Exposure was defined as current use of long-acting insulin analogues or NPH insulin, defined using a time-varying approach. The primary outcome was major adverse cardiovascular events (MACE; a composite endpoint of myocardial infarction, ischaemic stroke and cardiovascular death). We used a marginal structural Cox proportional hazards model to estimate the hazard ratio (HR) and 95% confidence interval (CI) for MACE with current use of long-acting insulin analogues versus NPH insulin, and in secondary analyses, by long-acting insulin molecule.. Our cohort included 57 334 patients. A total of 3494 MACE occurred over a mean follow-up of 1.6 years (incidence rate 37.4, 95% CI 36.2 to 38.7 per 1000 person-years). Long-acting insulin analogues were associated with a decreased risk of MACE compared to NPH insulin (HR 0.89, 95% CI 0.83 to 0.96).. Current use of long-acting insulin analogues is associated with a modestly reduced risk of MACE compared to current use of NPH insulin among patients with type 2 diabetes. This study could have important implications for drug plan managers and guideline-writing committees for recommendations of insulin treatment for type 2 diabetes.

Topics: Brain Ischemia; Cohort Studies; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Protamines; Retrospective Studies; Stroke

To explore details of the incidence and rates of daytime and nocturnal hypoglycaemia, levels of hypoglycaemia, and relationship to glycated haemoglobin (HbA1c), when comparing iGlarLixi versus premixed biphasic insulin aspart 30 (BIAsp 30) in the SoliMix randomized controlled trial.. This exploratory analysis of SoliMix used logistic regression and negative binomial regression analyses to assess between-treatment differences in the incidence and rates of hypoglycaemia by time of day. A negative binomial model was used to derive estimated annualized hypoglycaemia rates as a function of HbA1c.. iGlarLixi was associated with lower incidence and rates of American Diabetes Association Level 2 (<54 mg/dL [<3.0 mmol/L]) hypoglycaemia during both night and day versus BIAsp 30. Incidence and rates of Level 1 (<70 to ≥54 mg/dL [<3.9 to ≥3.0 mmol/L]) hypoglycaemia were also mostly shown to be reduced with iGlarLixi versus BIAsp 30. Severe (Level 3) events were too few for analysis (n = 3). iGlarLixi was associated with lower modelled event rates of Level 2 and Level 1 hypoglycaemia over a wide range of HbA1c levels versus BIAsp 30.. These results show that the lower HbA1c levels and weight benefit seen with iGlarLixi versus premixed BIAsp 30 in people with type 2 diabetes advancing their basal insulin therapy in the SoliMix trial are also accompanied by a lower risk of hypoglycaemia at any time of day and across a broad range of HbA1c levels.

Topics: Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Drug Combinations; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane

Though initiation of insulin results in a significant change in glycemic levels, treating patients without significant hypoglycemic events remains difficult in diabetes patients initiated with different insulin-based regimens. This study assessed the association of hypoglycemic incidence and glycemic control between NPH and premixed insulin regimens in patients with type 2 diabetes mellitus (T2DM).. This was a retrospective observational study in patients with T2DM who were treated with insulin-based therapy from 2015 to 2020 at the University of Gondar Comprehensive Specialized hospital. Average fasting blood glucose (FBG) between NPH and premixed insulin regimens was compared using an independent t-test. The Association of NPH and premixed insulin regimens with hypoglycemic incidences and glycemic control was examined by a logistic regression model. P < 0.05 was statistically significant.. From 405 participants, more than half (55.3%) were males with a mean age of 59.2(±9.1) years. Baseline mean HbA1C and FBG levels were 12.73(±1.1) % and 347.7(±48.5) mg/dl, respectively. Within a one-year follow-up period of insulin initiation, the rate of hypoglycemia was 13.1%. The incidence of hypoglycemia was significantly higher in patients initiated with premixed insulin compared with NPH insulin regimens (P < 0.001). After one year of insulin initiation, HbA1C decreased from 12.7 to 7.6 and from 12.8 to 7.3% and FBG levels decreased from 347.5 to 160.7 and from 348.2 to 147.3 mg/dl following initiation of NPH and premixed insulin, respectively. Patients treated with premixed-based insulin were found more likely to achieve target FBG compared with patients treated with NPH insulin regimens after one year of initiation (P = 0.02).. Premixed insulin-based regimen has found to have a higher hypoglycemic incidence, but a better level of glycemic control compared to NPH insulin-based therapy. Therefore, patients initiated with premixed insulin need to be highly vigilant and motivated to recognize the symptoms of hypoglycemia.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Ethiopia; Female; Glycated Hemoglobin; Glycemic Control; Hospitals; Humans; Hypoglycemia; Insulin; Insulin, Isophane; Insulin, Regular, Human; Male; Middle Aged

Previous studies have found that the risk of severe hypoglycemia does not differ between long-acting insulin analogs and neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes. However, these studies did not focus on patients 65 years or older, who are at an increased risk for hypoglycemia, or did not include patients with concomitant prandial insulin use.. To examine the risk of emergency department (ED) visits or hospitalizations for hypoglycemia among older community-residing patients with type 2 diabetes who initiated long-acting insulin or NPH insulin in real-world settings.. This retrospective, new-user cohort study assessed Medicare beneficiaries 65 years or older who initiated insulin glargine (n = 407 018), insulin detemir (n = 141 588), or NPH insulin (n = 26 402) from January 1, 2007, to July 31, 2019.. Insulin glargine, insulin detemir, and NPH insulin.. The primary outcome was time to first ED visit or hospitalization for hypoglycemia, defined using a modified validated algorithm. Propensity score-weighted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs. The risk of recurring hypoglycemia events was estimated using the Andersen-Gill model. Post hoc analyses were conducted investigating possible effect modification by age.. Of the 575 008 patients initiating use of insulin (mean [SD] age 74.9 [6.7] years; 53% female), 407 018 used glargine, 141 588 used detemir, and 26 402 used NPH insulin. The study included 7347 ED visits or hospitalizations for hypoglycemia (5194 for glargine, 1693 for detemir, and 460 for NPH insulin, with a median follow-up across the 3 cohorts of 0.37 years (interquartile range, 0.20-0.76 years). Initiation of glargine and detemir use was associated with a reduced risk of hypoglycemia compared with NPH insulin use (HR for glargine vs NPH insulin, 0.71; 95% CI, 0.63-0.80; HR, detemir vs NPH insulin, 0.72; 95% CI, 0.63-0.82). The HRs were similar for the recurrent event analysis. The protective association of long-acting insulin analogs varied by age and was not seen with concomitant prandial insulin use.. In this cohort study, initiation of long-acting analogs was associated with a lower risk of ED visits or hospitalizations for hypoglycemia compared with NPH insulin in older patients with type 2 diabetes in Medicare. However, this association was not seen with concomitant prandial insulin use.

Topics: Aged; Aged, 80 and over; Cohort Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Insulin, Isophane; Insulin, Long-Acting; Male; Proportional Hazards Models; Retrospective Studies

To determine whether basal insulin analogs reduce the rate of composite neonatal morbidity compared with neutral protamine Hagedorn (NPH) in women with type 2 diabetes mellitus (T2DM).. This was a retrospective cohort study of women with T2DM and singleton pregnancy at a single tertiary center. Primary outcome was a composite neonatal morbidity of any of the following: shoulder dystocia, large for gestational age, neonatal intensive care unit admission, neonatal hypoglycemia, or respiratory distress syndrome. Secondary outcomes were rates of maternal hypoglycemic events, hypertensive disorders, preterm birth, and primary cesarean delivery. Adjusted relative risk (aRR) and 95% confidence intervals (CI) were calculated.. Of 233 women with T2DM that met the inclusion criteria, 114 (49%) were treated with basal insulin analogs and 119 (51%) with NPH. The rate of composite neonatal morbidity was similar between groups (73 vs. 60%; aRR: 1.18; 95% CI: 0.92-1.51). There were no differences in the rates of maternal adverse outcomes between the groups. Basal insulin analog was associated with a lower rate of primary cesarean delivery as compared with NPH (21 vs. 36%; aRR: 0.44; 95% CI: 0.25-0.78).. Among pregnant women with T2DM managed with either basal or NPH insulin regimen, the rates of composite neonatal morbidity and maternal complications were similar.

Topics: Adult; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Infant, Newborn; Infant, Newborn, Diseases; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Logistic Models; Pregnancy; Pregnancy in Diabetics; Pregnancy Outcome; Premature Birth; Retrospective Studies; Young Adult

To assess whether initiation of insulin glargine (glargine), compared with initiation of NPH or insulin detemir (detemir), was associated with an increased risk of breast cancer in women with diabetes.. This was a retrospective new-user cohort study of female Medicare beneficiaries aged ≥65 years initiating glargine (203,159), detemir (67,012), or NPH (47,388) from September 2006 to September 2015, with follow-up through May 2017. Weighted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for incidence of breast cancer according to ever use, cumulative duration of use, cumulative dose of insulin, length of follow-up time, and a combination of dose and length of follow-up time.. Ever use of glargine was not associated with an increased risk of breast cancer compared with NPH (HR 0.97; 95% CI 0.88-1.06) or detemir (HR 0.98; 95% CI 0.92-1.05). No increased risk was seen with glargine use compared with either NPH or detemir by duration of insulin use, length of follow-up, or cumulative dose of insulin. No increased risk of breast cancer was observed in medium- or high-dose glargine users compared with low-dose users.. Overall, glargine use was not associated with an increased risk of breast cancer compared with NPH or detemir in female Medicare beneficiaries.

Topics: Age Factors; Age of Onset; Aged; Aged, 80 and over; Breast Neoplasms; Cohort Studies; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Incidence; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Medicare; Retrospective Studies; United States

NPH insulin holds its own against basal insulin analogs-and it's cheaper.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Emergency Service, Hospital; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin, Isophane; Insulin, Long-Acting

Overactivation and persistent chronic inflammation are the major pathogenic characteristics of diabetic-impaired healing, and diabetic wound healing can be promoted by stimulating the transition of macrophage phenotype from pro-inflammatory (M1) to anti-inflammatory (M2). Our previous studies found that the application of insulin induced an advanced initiation and resolution of inflammatory response. To further explore the mechanism, we have investigated the effect of insulin on macrophage phenotype switch utilizing a diabetic rat model and a human monocytic THP-1 cell. We have utilized the high glucose (HG) and HG plus insulin to stimulate the M1 macrophages derived from lipopolysaccharide-treated THP-1 cells. We studied the secretion of inflammatory mediator and related signaling pathways by using western blot test, immunofluorescence, and Rac1 pull-down assay. We have found that the production of pro-inflammatory mediators, which thereafter induced macrophage polarization toward M1 phenotype, has been elevated due to consistent HG exposure. HG plus insulin stimulation, on the other hand, promoted anti-inflammatory effects. Experiments performed on diabetic burn wounds indicated that the insulin modulated macrophages transition from M1 to M2 phenotype. We found that PI3K/Akt/Rac-1 and PPAR-γ signaling pathways are involved in the anti-inflammatory effect of insulin. Insulin inhibited HG-induced activation of p38, NF-κB, and STAT1 transcriptional activity by activating Akt-Rac-1 signaling. Moreover, insulin performs anti-inflammatory effects through upregulation of PPAR-γ expression and induced P38-mediated dephosphorylation of PPAR-γ (Ser112). In conclusion, insulin downregulates inflammatory response, regulates M1 macrophage transition in response to HG, and thus improves chronic wound healing.

Topics: Animals; Blood Glucose; Burns; Cell Plasticity; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Inflammation Mediators; Insulin, Isophane; Macrophages; Male; p38 Mitogen-Activated Protein Kinases; Phenotype; Phosphatidylinositol 3-Kinase; PPAR gamma; Proto-Oncogene Proteins c-akt; rac1 GTP-Binding Protein; Rats, Wistar; Signal Transduction; Skin; THP-1 Cells; Time Factors; Wound Healing

To evaluate the long-term cost-effectiveness of an intensification strategy with sodium-glucose co-transporter-2 (SGLT2) inhibitors (pathway 1) compared with NPH insulin (pathway 2) in patients with type 2 diabetes (T2D) in the United Kingdom who were not at goal on metformin and sitagliptin.. Cost-effectiveness analysis was performed using the well-established, validated IQVIA CORE Diabetes Model from the payer perspective over a patient's lifetime. Randomized clinical trials informed treatment effect measures, while public or published sources informed economic inputs. Scenario analyses of glycated haemoglobin (HbA1c), hypoglycaemia rate, body mass index effects, SGLT2 inhibitor cardiovascular protective effects, and population characteristics were conducted to assess the robustness of results.. Pathway 1 increased life-years and quality-adjusted life-years (QALYs) compared with pathway 2 (13.49 vs. 13.37, and 9.40 vs. 9.22, respectively). Additional drug costs in pathway 1 were offset by diabetes-related complication decreases, leading to slightly lower direct medical costs for pathway 1 (£25747 vs £26095). Pathway 1 was therefore cost-neutral (no interpretable incremental cost-effectiveness ratio), while improving clinical outcomes. Scenario analyses consistently showed cost-neutrality or cost-effectiveness of pathway 1. The highest result remained less than £3000/QALY, reflecting older patients (≥65 years) with lower baseline HbA1c (7%).. For UK patients with T2D not at goal on metformin and sitagliptin therapy, treatment intensification with SGLT2 inhibitors prior to NPH insulin is cost-neutral or cost-effective compared with immediate NPH insulin intensification.

Topics: Adult; Aged; Blood Glucose; Cost-Benefit Analysis; Diabetes Complications; Diabetes Mellitus, Type 2; Drug Costs; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin, Isophane; Male; Metformin; Middle Aged; Quality-Adjusted Life Years; Sitagliptin Phosphate; Sodium-Glucose Transporter 2 Inhibitors; United Kingdom

Although hypersensitivity reaction to insulin was supposed to be less-frequent with current insulin analogue, case reports with different types of allergic reactions to insulin analogue were still reported. The most common form is type I hypersensitivity reaction with IgE-mediated. Besides, type III (IgG and IgM-mediated) and type IV (T-cell mediated delayed reaction) hypersensitivity reactions were also reported. Here we presented a long-standing type 2 diabetes with insulin requirements with hypersensitivity reactions to insulin actrapid, insulin aspart, insulin glargine, insulin detemir, and biphasic insulin aspart 30. Insulin desensitization was performed as initial management but failed as skin biopsy with immunohistochemical staining proved type IV hypersensitivity reaction. We continued with the next treatment approach using subcutaneous injection with the mixture of biphasic insulin aspart 30 and dexamethasone to alleviate allergy, and the result was successful with steroid-free biphasic insulin aspart 30 injection eight months later. Besides, the treatment effect had lasted after ten years even with switched type of insulin analogue from biphasic insulin aspart 30 to insulin glargine and insulin aspart. The case report demonstrated a good example of how clinicians deal with the rare but important questions of hypersensitivity reactions to insulin analogue.

Topics: Biphasic Insulins; Dexamethasone; Diabetes Mellitus, Type 2; Drug Combinations; Female; Humans; Hypersensitivity, Delayed; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Middle Aged

To assess the financial consequences of different adoption rate of Biphasic Insulin Aspart (BIAsp) 30 instead of Biphasic Human Insulin (BHI) 30 for people with type 2 diabetes (T2DM) in Thailand from the payer's perspective.. The Excel-based International T2DM Budget Impact Model over a 3-year period was used. The cohort was the T2DM patients who received treatment from government hospitals under the Universal Health Coverage Scheme. Demographic, the adverse events, and the costs were derived from published studies in Thailand. Efficacy was based on meta-analysis. Adoption rates were assumed to increase each year. Net budget impact (NBI) and one-way sensitivity were analyzed.. Hypoglycemia costs were lower in BIAsp 30 compared with BHI 30. The NBI per year was 26,511,269 THB (771,349 USD) for year 1, 52,181,133 THB (1,518,218 USD) for year 2, and 76,189,608 THB (2,216,747 USD) for year 3. The NBI per insulin user per year was 33.45 THB (0.97 USD), 67.27 THB (1.96 USD), 101.49 THB (2.95 USD) from year 1 to year 3, respectively Conclusions: Lower rate of hypoglycemia with BIAsp 30 than those treated with BHI 30 generates cost savings resulting in significant deduction in the additional acquisition cost of BIAsp 30. Therefore, the NBI per insulin user per year has become small.

Topics: Biphasic Insulins; Budgets; Cohort Studies; Cost Savings; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Outcome Assessment, Health Care; Thailand; Treatment Outcome

To compare dipeptidyl peptidase-4 (DPP-4) inhibitors with neutral protamine Hagedorn (NPH) insulin, in terms of effectiveness and safety for the management of patients with type 2 diabetes mellitus (DM2) not controlled on metformin and sulfonylureas.. A retrospective cohort study of individuals with DM2 newly dispensed with either DPP-4 inhibitors or NPH as third-line therapy, after metformin and sulfonylurea. Treatment discontinuation, macrovascular outcomes, and hypoglycemia were compared using multivariable Cox regression models, adjusted for sex, age, year of cohort entry, place of residence, hypertension, past history of hypoglycemia, diabetic ketoacidosis, comorbidities, and number of visits to emergency departments, outpatient physician, and hospitalizations.. Treatment discontinuation and hypoglycemia occurred more frequently with NPH than with DPP-4 inhibitor users. In the adjusted Cox model, the use of NPH compared to that of DPP-4 inhibitors was associated with a higher risk of discontinuation (HR: 1.33; 95% CI 1.27-1.40) and hypoglycemia (HR: 2.98; 95% CI 2.72-3.28). Risk of cardiovascular events was similar across groups.. This real-world analysis suggests that DM2 patients initiating third-line therapy with NPH have poorer control of diabetes when compared to DPP-4 inhibitor initiators.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin, Isophane; Male; Metformin; Middle Aged; Retrospective Studies; Sulfonylurea Compounds; Withholding Treatment

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

In clinical trials of patients with type 2 diabetes, long-acting insulin analogs modestly reduced the risk of nocturnal hypoglycemia compared with human neutral protamine Hagedorn (NPH) insulin, but cost 2 to 10 times more. Outcomes in clinical practice may differ from trial results.. To compare the rates of hypoglycemia-related emergency department (ED) visits or hospital admissions associated with initiation of long-acting insulin analogs vs human NPH insulin in patients with type 2 diabetes.. A retrospective observational study using data from Kaiser Permanente of Northern California from January 1, 2006, through September 30, 2015. Patients with type 2 diabetes who initiated a long-acting insulin analog or NPH insulin were included and censored at death, loss of health plan coverage, change in insulin treatment, or study end on September 30, 2015.. Initiation of basal insulin analogs (glargine or detemir) vs NPH insulin.. The primary outcome was the time to a hypoglycemia-related ED visit or hospital admission and the secondary outcome was the change in hemoglobin A1c level within 1 year of insulin initiation.. There were 25 489 patients with type 2 diabetes who initiated basal insulin therapy (mean age, 60.2 [SD, 11.8] years; 51.9% white; 46.8% female). During a mean follow-up of 1.7 years, there were 39 hypoglycemia-related ED visits or hospital admissions among 1928 patients who initiated insulin analogs (11.9 events [95% CI, 8.1 to 15.6] per 1000 person-years) compared with 354 hypoglycemia-related ED visits or hospital admissions among 23 561 patients who initiated NPH insulin (8.8 events [95% CI, 7.9 to 9.8] per 1000 person-years) (between-group difference, 3.1 events [95% CI, -1.5 to 7.7] per 1000 person-years; P = .07). Among 4428 patients matched by propensity score, the adjusted hazard ratio was 1.16 (95% CI, 0.71 to 1.78) for hypoglycemia-related ED visits or hospital admissions associated with insulin analog use. Within 1 year of insulin initiation, hemoglobin A1c level decreased from 9.4% (95% CI, 9.3% to 9.5%) to 8.2% (95% CI, 8.1% to 8.2%) after initiation of insulin analogs and from 9.4% (95% CI, 9.3% to 9.5%) to 7.9% (95% CI, 7.9% to 8.0%) after initiation of NPH insulin (adjusted difference-in-differences for glycemic control, -0.22% [95% CI, -0.09% to -0.37%]).. Among patients with type 2 diabetes, initiation of a basal insulin analog compared with NPH insulin was not associated with a reduced risk of hypoglycemia-related ED visits or hospital admissions or with improved glycemic control. These findings suggest that the use of basal insulin analogs in usual practice settings may not be associated with clinical advantages for these outcomes.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Emergency Service, Hospital; Female; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Male; Middle Aged; Retrospective Studies

Reasonable glycemic control is difficult to achieve in patients with diabetes mellitus (DM) receiving continuous enteral nutrition therapy (CENT). There are no solid evidence-based medicine guidelines regarding this issue in these patients. The purpose of this study was to determine if the use of a basal-bolus insulin regimen is more effective than neutral protamine Hagedorn (NPH) insulin alone in controlling blood glucose in non-critically ill patients with DM receiving CENT. We performed a retrospective, records-based review comparing basal-bolus with NPH insulin regimen in these patients, hospitalized in the internal medicine wards in our hospital. Number of hypoglycemic episodes, mean blood glucose, and time-to-target (time needed to reach 3 successive glucose readings in the appropriate target of 140-180 mg/dL) were evaluated in each regimen. Mean blood glucose was 199.22 mg/dL (95% confidence interval [CI], 179.8-218.5 mg/dL) in the basal-bolus vs 190.73 mg/dL (95% CI, 172.1-209.2 mg/dL) in the NPH insulin regimen ( P = .538). Time-to-target was an average of 3.65 ± 1.75 days in the basal-bolus group and 4.33 ± 2.42 days in the NPH group ( P = .364). There were no statistically significant differences in frequency of hypoglycemia ( P = .364). Rate of death was high (around 40%) in both groups. We conclude that hospitalized hyperglycemic patients receiving CENT can be treated by either basal-bolus or NPH insulin regimens. However, the overall glucose levels remain elevated during hospitalization irrespective of the insulin therapy. There is an urgent need to define glucose targets in this population of patients and to evaluate prospectively head-to-head different insulin protocols.

Topics: Aged; Aged, 80 and over; Blood Glucose; Critical Illness; Diabetes Mellitus, Type 2; Enteral Nutrition; Evidence-Based Medicine; Female; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin, Isophane; Male; Middle Aged; Retrospective Studies

Purpose The association between long-acting insulin analogs and increased breast cancer risk is uncertain, particularly with the short follow-up in previous studies. We assessed this risk long term in women with type 2 diabetes. Methods A population-based cohort of women 40 years or older, all of whom were treated with long-acting (glargine, detemir) or neutral protamine Hagedorn (NPH) insulin between 2002 and 2012, was formed using the United Kingdom's Clinical Practice Research Datalink. Women were followed until February 2015 or breast cancer diagnosis. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95% CIs of incident breast cancer, comparing long-acting insulin analogs with NPH overall, as well as by duration and cumulative dose. Results The cohort included 22,395 women who received insulin treatment, with 321 incident breast cancer events occurring during up to 12 years of follow-up (incidence rate 3.3 per 1,000 person-years). Compared with NPH insulin, insulin glargine was associated with an increased risk of breast cancer (HR, 1.44; 95% CI, 1.11 to 1.85), mainly increasing 5 years after glargine initiation (HR, 2.23; 95% CI, 1.32 to 3.77) and after > 30 prescriptions (HR, 2.29; 95% CI, 1.26 to 4.16). The risk was particularly elevated among prior insulin users (HR, 1.53; 95% CI, 1.10 to 2.12) but not for new users, which included fewer patients and for which one cannot rule out an HR of 1.81. The risk associated with insulin detemir was not significantly elevated (HR, 1.17; 95% CI, 0.77 to 1.77). Conclusion Long-term use of insulin glargine is associated with an increased risk of breast cancer in women with type 2 diabetes. The risk associated with insulin detemir remains uncertain because there are fewer users of this insulin.

Topics: Aged; Breast Neoplasms; Canada; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Incidence; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Middle Aged; Risk

To evaluate the impact of 6 month hypoglycemia on treatment discontinuation and hospitalization of patients initiating basal insulin for type 2 diabetes (T2D) in real-world practice.. This was a retrospective cohort study of patient-level data using electronic medical records (EMRs) in the Predictive Health Intelligence diabetes dataset. Data from adult patients with T2D initiating basal insulin glargine, insulin detemir, or Neutral Protamine Hagedorn insulin between January 2008 and March 2014 was analyzed. The date of first basal insulin prescription in an outpatient setting was the index date. A 12 month baseline prior to the index date was established; follow-up was 6-24 months from the index date. Patients were assigned to cohorts by experience of hypoglycemia (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code or blood glucose test) in the first 6 months following the index date; with hypoglycemia and without hypoglycemia cohorts were compared for basal insulin treatment discontinuation and hospitalization.. Overall, 49,062 patients were included; 5159 (10.5%) experienced hypoglycemia in the 6 months following basal insulin initiation. In the first 12 months, 68.1% of patients in the with hypoglycemia cohort discontinued basal insulin versus 53.9% in the without hypoglycemia cohort (p < .0001); more patients in the with hypoglycemia cohort had at least one hospitalization in the first year of follow-up (50.1% vs. 14.6%; p < .0001).. Patients with hypoglycemia soon after initiating basal insulin are at greater risk of discontinuation of their basal insulin therapy and hospitalization versus those who did not have hypoglycemic events within the first 6 months of basal insulin initiation. A limitation of this study is that it was a retrospective analysis of EMR data and the study may not be representative of all US patients with T2D on basal insulin and it cannot be assumed that every hypoglycemic event was recorded.

Topics: Aged; Diabetes Mellitus, Type 2; Electronic Health Records; Female; Follow-Up Studies; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Male; Middle Aged; Retrospective Studies; Risk

To compare short-term basal insulin therapy persistence and its predictors in Poland and Germany.. Persistence was defined as proportions of patients remaining on the initial basal insulin (analogs: Poland: n = 6,889, Germany: n = 454,067; neutral protamine Hagedorn (NPH) insulins: Poland: n = 50,761, Germany: n = 226,064) over 2 years based on nationwide prescription databases (LRx; IMS Health) in Poland and Germany from 2013 to 2015. Persistence was evaluated by Kaplan-Meier curves (log-rank tests). Risk of discontinuation of initial basal insulin was investigated using Cox regression models adjusting for age, sex, comedication with other glucose-lowering agents and baseline or comedication with antihypertensives, lipid-lowering drugs, antidepressants, and antiepileptics.. In Poland, 2-year persistence was 83.0% in analog insulin and 73.3% in NPH users (p < 0.001). In Germany, persistence was also higher in patients with analog insulins (92.6% vs. 79.0%; p < 0.001). Analog insulin users were less likely to discontinue basal insulin compared with NPH users (adjusted hazard ratio (95%CI): Poland: 0.73 (0.67 - 0.79); Germany: 0.27 (0.27 - 0.28)). Higher age (> 75 vs. ≤ 60 years: Poland: 1.24 (1.16 - 1.33), Germany: 1.09 (1.07 - 1.11)) and GLP-1 receptor agonist use (Poland: 2.76 (1.38 - 5.53), Germany: 1.21 (1.16 - 1.26)) were related to higher risk of discontinuation. Male sex, metformin, sulfonylurea, thiazolidinedione, and short-acting insulin prescriptions as well as antihypertensive, anti-epileptic, and lipid-lowering drug use were associated with lower risk of discontinuation in both countries (all p < 0.05).. This real-world study shows that both in Poland and Germany treatment persistence of newly-prescribed basal insulin is influenced by type of insulin (analog vs. NPH) and by glucose-lowering and other comedications.
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Topics: Aged; Biomarkers; Blood Glucose; Chi-Square Distribution; Comorbidity; Databases, Factual; Diabetes Mellitus, Type 2; Drug Prescriptions; Female; Germany; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Kaplan-Meier Estimate; Male; Medication Adherence; Middle Aged; Multivariate Analysis; Poland; Polypharmacy; Proportional Hazards Models; Risk Factors; Time Factors; Treatment Outcome

To compare glucose control and safety of different basal insulin therapies (BI, including Insulin NPH, glargine and detemir) in real-world clinical settings based on a large-scale registry study.. In this multi-center 6-month prospective observational study, patients with type 2 diabetes (HbA1c ≥ 7%) who were uncontrolled by oral anti-diabetic drugs (OADs) and were willing to initiate BI therapy were enrolled from 209 hospitals within 8 regions of China. Type and dose of BI were at the physician's discretion and the patients' willingness. Interviews were conducted at 0 months (visit 1), 3 months (visit 2) and 6 months (visit 3). Outcomes included change in HbA1c, hypoglycemia rate and body weight from baseline at 6 months.. A total of 16 341 and 9002 subjects were involved in Intention-To-Treat (ITT) and per-protocol (PP) analysis, respectively. After PS regression adjustment, ITT analysis showed that reduction in HbA1c in glargine (2.2% ± 2.1%) and detemir groups (2.2% ± 2.1%) was higher than that in the NPH group (2.0% ± 2.2%) (P < .01). The detemir group had the lowest weight gain (-0.1 ± 2.9 kg) compared with the glargine (+0.1 ± 3.0 kg) and NPH (+0.3 ± 3.1 kg) groups (P < .05). The glargine group had the lowest rate of minor hypoglycaemia, while there was no difference in severe hypoglycaemia among the 3 groups. The results observed in PP analyses were consistent with those in ITT analysis.. In a real-world clinical setting in China, treatment with long-acting insulin analogues was associated with better glycaemic control, as well as less hypoglycaemia and weight gain than treatment with NPH insulin in type 2 diabetes patients. However, the clinical relevance of these observations must be interpreted with caution.

Topics: China; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Monitoring; Drug Resistance; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Intention to Treat Analysis; Lost to Follow-Up; Prospective Studies; Registries; Severity of Illness Index; Weight Gain

To identify patient-related characteristics and other impact factors predicting early discontinuation of basal insulin therapy in type 2 diabetes in primary care.. A total of 4837 patients who started basal insulin therapy (glargine: n=3175; NPH: n=1662) in 1072 general and internal medicine practices throughout Germany were retrospectively analyzed (Disease Analyser Database: 01/2008-03/2014). Early discontinuation was defined as switching back to oral antidiabetic drugs (OAD) therapy within 90 days after first basal insulin prescription (index date, ID). Patient records were assessed 365 days prior and post ID. Logistic regression models were used to adjust for age, sex, diabetes duration, diabetologist care, disease management program participation, HbA1c, and comorbidity.. Within 3 months after ID, 202 (6.8%) of glargine patients switched back to OAD (NPH: 130 (8.5%); p<0.05). In multivariable logistic regression, predictors of early basal insulin discontinuation were ≥1 documented hypoglycemia before ID (adjusted Odds ratio; 95% CI: 2.20; 1.27-3.82), diagnosed depression (1.31; 1.01-1.70) and referrals to specialists within 90 days after ID (2.06; 1.61-2.63). Diabetologist care (0.57; 0.36-0.89) and glargine treatment (vs. NPH: 0.78; 0.61-0.98) were related to a lower odds of having early insulin discontinuation.. Less than 10% of type 2 diabetes patients switched back to oral antidiabetic drugs within 90 days after start of basal insulin therapy. In particular, patients with baseline depression and frequent or severe hypoglycemia have a higher likelihood for early discontinuation of basal insulin, whereas use of insulin glargine and diabetologist care are related to an increased chance of continuous insulin treatment.

Topics: Aged; Aged, 80 and over; Biomarkers; Blood Glucose; Chi-Square Distribution; Depression; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Substitution; Female; Germany; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Primary Health Care; Referral and Consultation; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome

Insulin degludec/insulin aspart (IDegAsp) is a soluble coformulation of the basal analog insulin degludec and the rapid-acting prandial insulin aspart in a single injection. The present combined analysis of two Phase 3a trials compared the incidence of hypoglycemia in participants treated twice daily with IDegAsp or biphasic insulin aspart 30 (BIAsp 30).. Hypoglycemia data were analyzed from two similarly designed randomized controlled open-label treat-to-target Phase 3a clinical trials of adults with type 2 diabetes (T2D). Participants were treated twice daily with IDegAsp or BIAsp 30, with breakfast and their main evening meal.. Over 26 weeks, the rates of overall confirmed, nocturnal confirmed and severe hypoglycemic events were 19%, 57%, and 39% lower, respectively, with IDegAsp (n = 504) than BIAsp 30 (n = 364); estimated rate ratios were 0.81 (95% confidence interval [CI] 0.67, 0.98; P = 0.0341), 0.43 (95% CI 0.31, 0.59; P = 0.0001), and 0.61 (95% CI 0.26, 1.45; P = NS). The between-treatment differences were more pronounced during the maintenance period (≥16 weeks); compared with BIAsp 30, rates of overall confirmed, nocturnal confirmed and severe hypoglycemic events with IDegAsp were 0.69 (95% CI 0.55, 0.87; -31%; P = 0.0015); 0.38 (95% CI 0.25, 0.58; -62%; P < 0.0001), and 0.16 (95% CI 0.04, 0.59; -84%; P = 0.0061), respectively.. Compared with BIAsp 30 twice daily, IDegAsp twice daily provided similar improvements in glycemic control with a lower risk of hypoglycemia, particularly nocturnal hypoglycemia, in subjects with T2D previously treated with insulin.

Topics: Aged; Biphasic Insulins; Blood Glucose; Clinical Trials, Phase III as Topic; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Insulin, Long-Acting; Maintenance Chemotherapy; Male; Middle Aged; Multicenter Studies as Topic; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic; Risk Factors

Topics: Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Humans; Hypoglycemic Agents; Insulin, Isophane; Insulin, Long-Acting

Even though Insulin glargine (IGlar) has been available and used in other countries for more than a decade, it has not been adopted into Thai national formulary. This study aimed to evaluate the long-term cost effectiveness of IGlar versus neutral protamine Hagedorn (NPH) insulin in type 2 diabetes from the perspective of Thai Health Care System.. A validated computer simulation model (the IMS CORE Diabetes Model) was used to estimate the long-term projection of costs and clinical outcomes. The model was populated with published characteristics of Thai patients with type 2 diabetes. Baseline risk factors were obtained from Thai cohort studies, while relative risk reduction was derived from a meta-analysis study conducted by the Canadian Agency for Drugs and Technology in Health. Only direct costs were taken into account. Costs of diabetes management and complications were obtained from hospital databases in Thailand. Both costs and outcomes were discounted at 3 % per annum and presented in US dollars in terms of 2014 dollar value. Incremental cost-effectiveness ratio (ICER) was calculated. One-way and probabilistic sensitivity analyses were also performed.. IGlar is associated with a slight gain in quality-adjusted life years (0.488 QALYs), an additional life expectancy (0.677 life years), and an incremental cost of THB119,543 (US$3522.19) compared with NPH insulin. The ICERs were THB244,915/QALY (US$7216.12/QALY) and THB176,525/life-year gained (LYG) (US$5201.09/LYG). The ICER was sensitive to discount rates and IGlar cost. At the acceptable willingness to pay of THB160,000/QALY (US$4714.20/QALY), the probability that IGlar was cost effective was less than 20 %.. Compared to treatment with NPH insulin, treatment with IGlar in type 2 diabetes patients who had uncontrolled blood glucose with oral anti-diabetic drugs did not represent good value for money at the acceptable threshold in Thailand.

Topics: Computer Simulation; Cost-Benefit Analysis; Costs and Cost Analysis; Diabetes Complications; Diabetes Mellitus, Type 2; Drug Costs; Female; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Life Expectancy; Male; Markov Chains; Middle Aged; Monte Carlo Method; Pharmacopoeias as Topic; Quality-Adjusted Life Years; Thailand

Basal insulins are first line injectable therapy by all international guidelines. Basal insulins can be used alone, in combination with metformin, dual or triple oral therapy, glucagon-like peptide receptor agonists, or prandial insulin. However, all basal insulins are not similar. This article proposes objective parameters, and suggests a simple checklist, using history, physical examination, and investigations, to help choose the appropriate preparation, viz degludec, detemir, glargine or NPH insulin, for persons requiring basal insulin.

Topics: Checklist; Clinical Decision-Making; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Metformin; Patient-Centered Care

Insulin therapy in type 2 diabetes may increase mortality and cancer incidence, but the impact of different types of basal insulins on these endpoints is unclear. Compared to the traditional NPH insulin, the newer, longer-acting insulin analogues detemir and glargine have shown benefits in randomized controlled trials. Whether these advantages translate into lower mortality among users in real life is unknown.. To estimate the differences in all-cause and cause-specific mortality rates between new users of basal insulins in a population-based study in Finland.. 23 751 individuals aged ≥40 with type 2 diabetes, who initiated basal insulin therapy in 2006-2009 were identified from national registers, with comprehensive data for mortality, causes of death, and background variables. Propensity score matching was performed on characteristics. Follow-up time was up to 4 years (median 1.7 years).. 2078 deaths incurred. With NPH as reference, the adjusted HRs for all-cause mortality were 0.39 (95% CI, 0.30-0.50) for detemir, and 0.55 (95% CI, 0.44-0.69) for glargine. As compared to glargine, the HR was 0.71 (95% CI, 0.54-0.93) among detemir users. Compared to NPH, the mortality risk for both cardiovascular causes as well as cancer were also significantly lower for glargine, and especially for detemir in adjusted analysis. Furthermore, the results were robust in various sensitivity analyses.. In real clinical practice, mortality was substantially higher among users of NPH insulin as compared to insulins detemir or glargine. Considering the large number of patients who require insulin therapy, this difference in risk may have major clinical and public health implications. Due to limitations of the observational study design, further investigation using an interventional study design is warranted.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Cause of Death; Cohort Studies; Databases, Factual; Diabetes Mellitus, Type 2; Female; Finland; Gastrointestinal Diseases; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Neoplasms; Risk

The addition of a single injection of insulin to the oral drugs (basal supported oral therapy; BOT) has been shown to greatly reduce blood glucose levels. The intermediate-acting NPH insulin (NPH) and the long-acting insulin glargine (Lantus(®)) have been compared for use in BOT in numerous clinical trials; however, their efficacy and safety in a real-life setting have not been described.. TIP (therapeutic benefits of patients on insulin glargine vs. NPH insulin being poorly controlled on prior short-time basal-insulin supported therapy with NPH insulin or insulin glargine) is a non-interventional, multicentre, observational study over 24 weeks. A total of 2629 patients were enrolled and 1931 were fully evaluable (1614 insulin glargine, 303 NPH insulin). Propensity scoring (PSM) was used to match 570 patients into 2 similar cohorts of 285 patients.. In the PSM cohort, a slightly greater reduction in FBG and HbA1c levels was seen in the insulin glargine group compared to the NPH group. A weight loss, which was slightly more pronounced in insulin glargine patients despite receiving a lower insulin dose relative to the NPH group, was seen in both the groups. Additionally, hypoglycaemia, including nocturnal and severe events, was more prevalent in the patients receiving BOT with NPH. The occurrence of new micro- or macro-vascular complications and adverse events was low for both groups. A large proportion of patients changed from NPH therapy to insulin glargine therapy during the study, which was mainly attributable to insufficient glucose modulation. Improvements in quality of life and treatment satisfaction were found for both types of insulin.. This observational study provides evidence from a real-life setting that BOT with insulin glargine provides slightly greater reductions in weight, FBG and HbA1c levels, with a lower risk of hypoglycaemia than patients receiving NPH. This conclusion indicates that insulin glargine may be preferable to NPH insulin for BOT.

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Male; Middle Aged; Quality of Life

Long-term, high dosage protamine zinc insulin (PZI) treatments produce adverse reactions. The trace element selenium (Se) is a candidate for the prevention of diabetes due to anti-oxidative stress activity and the regulation of glycometabolism. In this study, we aimed to investigate the anti-diabetic effects of a combination of PZI and Se on type 2 diabetes. Diabetic KKAy mice were randomized into the following groups: model group and groups that were subcutaneously injected with PZI, Se, high or low dose PZI + Se for 6 weeks. PZI combined with Se decreased the body weight and fasting blood glucose levels. Moreover, this treatment also improved insulin tolerance, as determined by the reduced values from the oral glucose tolerance test and insulin tolerance test, and increased insulin levels and insulin sensitivity index. PZI combined with Se ameliorated skeletal muscle and β-cell damage and the impaired mitochondrial morphology. Oxidative stress was also reduced. Furthermore, PZI combined with Se upregulated phosphatidylinositol 3-kinase (PI3K) and downregulated protein tyrosine phosphatase 1B (PTP1B). Importantly, the low dosage combination produced effects similar to PZI alone. In conclusion, PZI combined with Se improved glycometabolism and ameliorated the tissue and mitochondrial damage, which might be associated with the PI3K and PTP1B pathways.

Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Gene Expression Regulation; Glucose Tolerance Test; Hypoglycemic Agents; Insulin; Insulin-Secreting Cells; Insulin, Isophane; Mice; Mitochondria; Muscle Cells; Muscle, Skeletal; Oxidative Stress; Random Allocation; Sodium Selenite

To compare the effect on metabolic control of treatment with conventional and analogue insulins for patients with diabetes mellitus.. Retrospective cohort study held in cities of Colombia (Pereira and Manizales). People insured by the paid healthcare system, who were diagnosed with diabetes mellitus type 1 and 2, and treated with conventional and analogue insulin for at least 6 months prior to the start of the study were sampled and followed up for 18 months. Data were collected from clinical records for each patient. Treatment groups were compared according to the type of insulin received.. A total of 313 patients were included; overall, 56.9% were women and the mean age was 57.3 years. No statistically significant difference was found in glycosylated haemoglobin reduction at 3, 6 and 18 months when comparing patients receiving glargine vs NPH insulin (P=.403) and NPH plus zinc crystalline insulin vs glargine plus glulisine (P=.514). The percentage of patients with metabolic control increased from 27.8% to 34.2% during follow-up with all types of insulin.. Insulin analogues were not superior to human insulin for glycaemic control. A significant proportion of patients did not attain the treatment goals; therefore, it is necessary to implement measures to improve the monitoring and control of diabetes mellitus.

Topics: Adult; Blood Glucose; Cohort Studies; Colombia; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Retrospective Studies

The aim of this analysis was to investigate total healthcare costs, HbA1c, and weight changes over a 36-month period in patients with type 2 diabetes initiated on NPH or long-acting insulin analogs.. Electronic patient data from 479 general practices in the UK (THIN database) were examined for new users of glargine (n = 794), detemir (n = 252), or NPH insulin (n = 430). Annualized healthcare costs and clinical outcomes in years 1, 2, and 3 following insulin initiation were quantified and compared with baseline, using ANOVA and linear regression models.. A significant difference (p < 0.05) in total healthcare costs increases at year 1 vs baseline was observed between glargine and detemir, detemir and NPH, but not between glargine and NPH (increase: +£486, +£635, and +£420 for glargine, detemir, and NPH users, respectively). However, increases by year 3 were not significantly different between the insulins. A propensity score analysis comparing analog and NPH insulin showed that, following insulin initiation, increases in costs were higher with insulin analogs at year one (+£220), but this difference decreased over time in each year following insulin initiation (+£168 and +£146, respectively, for years 2 and 3). HbA1c reductions were not significantly different between the groups at all time points. Differences in weight gain between glargine and NPH were statistically significant at year 1 (0.87 kg vs 1.11 kg) and year 3 (1.15 kg vs 1.57 kg), but other estimates of between-group differences in weight gain were non-significant.. Following insulin initiation, the difference in healthcare costs of long-acting analogs compared to NPH insulin was transient. By year 3, the cost differences were not significantly different between the two cohorts, driven by an observed reduction in the cost of self-monitoring of blood glucose (SMBG) in the analog group and an increase in the cost of bolus insulin in the NPH group.

Topics: Body Mass Index; Body Weight; Comorbidity; Costs and Cost Analysis; Diabetes Mellitus, Type 2; Electronic Health Records; Female; Glycated Hemoglobin; Health Care Costs; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Multivariate Analysis; Outcome Assessment, Health Care; Propensity Score; United Kingdom

Poor glycemic control and the resulting development of complications of type 2 diabetes (DM2T) increase treatment costs. If adequate glycemic control cannot be achieved by lifestyle modifications and oral antidiabetic (OAD) therapy, initiation of insulin therapy is recommended. Cost effectiveness of basal insulins of the type NPH or glargine in combination with OAD for the treatment of DM2T was examined in a number of pharmacoeconomic studies. However, none of these studies were conducted in the Czech Republic. Therefore, the aim of the project POET2 was to compare annual direct medical costs of treating DM2T after addition of insulin NPH or glargine to OAD therapy in a clinical practice setting in the Czech Republic.. Data collected from 1967 patients who met the criteria for inclusion into the non-interventional prospective registry POET2 (DM2T, ongoing OAD therapy, glycated hemoglobin HbA1c > 6 % IFCC) and who were observed for 12 months following the start of insulin therapy (glargine: n = 1061 vs NPH: n = 906) were analysed. Costs of treatment were analysed from the perspective of health insurance companies and included costs of medication, medical devices and medical procedures.. In both treatment groups a reduction of HbA1c (glargine group: by 1.77 % IFCC vs NPH group: by 1.73 % IFCC) and fasting plasma glucose (glargine group: by 3.67 mmol/l vs NPH group: by 3.63 mmol/l) was observed. Insulin glargine therapy was associated with the incidence of a significantly lower number of documented symptomatic hypoglycemic events (glargine group: 0.840 events per patient and year of treatment vs. NPH group: 1.053 events per patient and year of treatment; p < 0.05). Overall annual direct medical costs associated with the initiation of basal insulin treatment were higher on average by 2547.07 CZK among patients treated with insulin glargine (glargine group: 12173.09 ± 4169.44 CZK vs NPH group: 9626.02 ± 3432.79 CZK; p < 0.001) due to higher costs of medication (glargine group: 7992.97 ± 4001.81 CZK vs NPH group: 3784.2 ± 3181.48 CZK; p < 0.001). By contrast, costs of medical devices (glargine group: 2332.08 ± 917.84 CZK vs NPH group: 3893.95 ± 989.79 CZK; p < 0.001) and medical procedures (glargine group: 1848.04 ± 684.89 CZK vs NPH group: 1947.87 ± 685.43 CZK; p < 0.001) were lower among patients treated with insulin glargine.. Addition of basal insulin to OAD therapy was an efficacious therapeutic intervention for the treatment of DM2T in a clinical practice setting in the Czech Republic. Overall annual direct medical costs were higher among patients treated with insulin glargine than among patients treated with insulin NPH. However, costs of medical devices and medical procedures were lower in the insulin glargine group. In addition, incidence of hypoglycemia was significantly lower among patients treated with insulin glargine.

Topics: Adult; Aged; Czech Republic; Diabetes Mellitus, Type 2; Direct Service Costs; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Middle Aged; Prospective Studies; Registries

To compare persistence and its predictors in type 2 diabetes patients in primary care, initiating either basal supported oral therapy (BOT) or intensified conventional therapy (ICT) with glargine, detemir, or NPH insulin.. In the BOT cohort, 1398 glargine (mean age: 68 years), 292 detemir (66 years), and 874 NPH (65 years) users from 918 practices were retrospectively analyzed (Disease Analyzer, Germany: 2008-2012). The ICT group incorporated 866 glargine (64 years), 512 detemir (60 years), and 1794 NPH (64 years) new users. Persistence was defined as proportion of patients remaining on the initial basal insulin (glargine, detemir and NPH insulin) over 2 years. Persistence was evaluated by Kaplan-Meier curves (log-rank tests) and Cox regression adjusting for age, sex, diabetes duration, antidiabetic co-therapy, comorbidities, specialist care, and private health insurance.. In BOT, two-year persistence was 65%, 53%, and 59% in glargine, detemir, and NPH users, respectively (p<0.001). In ICT, persistence was higher without differences between groups: 84%, 85%, 86% in glargine, detemir, and NPH, respectively (p=0.536). In BOT, detemir and NPH users were more likely to discontinue basal insulin compared with glargine (detemir vs. glargine: adjusted Hazard Ratio; 95% CI: 1.56; 1.31-1.87; NPH vs. glargine: 1.22; 1.07-1.38). Heart failure (1.39; 1.16-1.67) was another predictor of non-persistence, whereas higher age (per year: 0.99; 0.98-0.99), metformin (0.61; 0.54-0.69), and sulfonylurea co-medication (0.86; 0.77-0.97) were associated with lower discontinuation.. In BOT, treatment persistence among type 2 diabetes patients initiating basal insulin is influenced by type of insulin, antidiabetic co-medication, and patient characteristics.

Topics: Administration, Oral; Aged; Databases, Factual; Diabetes Mellitus, Type 2; Female; Germany; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Kaplan-Meier Estimate; Male; Medication Adherence; Middle Aged; Multivariate Analysis; Primary Health Care; Proportional Hazards Models; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome

In the earlier stage of type 2 diabetes, the disease can be managed by life-style modification with or without oral antidiabetic agents. However, as the disease progress, most patients eventually require insulin treatment to maintain good glycemic/control. Optimal insulin therapy should mimic the normal physiologic secretory pattern. As for ideal basal insulin, to maintain desirable pre-prandial glucose levels, duration of action should be long enough, profiles such as flat time-action and less day-to-day variation would be mandatory. This article discusses the usefulness and limitations of basal insulin therapy in type 2 diabetes comparing NPH insulin, insulin detemir, insulin glargin and insulin degludec.

Topics: Diabetes Mellitus, Type 2; Humans; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

Topics: Diabetes Mellitus, Type 2; Direct Service Costs; Female; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

Long-acting insulin analogues (eg, insulin glargine and insulin detemir) are an alternative to neutral protamine Hagedorn (NPH) insulin for maintaining glycemic control in patients with diabetes. Clinical trials comparing analogue insulin and NPH have neither been adequately powered nor had sufficient follow-up to examine long-term health outcomes.. To compare the effects of NPH and long-acting insulin analogues on long-term outcomes.. This retrospective observational study relied on administrative data from the Veterans Health Administration and Medicare from 2000 to 2010. Local variations in analogue insulin prescribing rates were used in instrumental variable models to control for confounding. Outcomes were assessed using survival models.. The study population included US veterans dually enrolled in Medicare who received at least 1 prescription for oral diabetes medication and then initiated long-acting insulin between 2001 and 2009. Outcomes included ambulatory care-sensitive condition (ACSC) hospitalizations and mortality.. There was no significant relationship between type of insulin and ACSC hospitalization or mortality. The hazard ratio for mortality of individuals starting a long-acting analogue insulin was 0.97 (95% CI, 0.85-1.11), and was 1.05 (95% CI, 0.95-1.16) for ACSC hospitalization. Differences in risk remained insignificant when predicting diabetes-specific ACSC hospitalizations, but starting on long-acting analogue insulin significantly increased the risk of a cardiovascular-specific ACSC hospitalization.. We found no consistent difference in long-term health outcomes when comparing use of long-acting insulin analogues and NPH insulin. The higher cost of analogue insulin without demonstrable clinical benefit raises questions of its cost-effectiveness in the treatment of patients with diabetes.

Topics: Aged; Diabetes Mellitus, Type 2; Female; Hospitalization; Humans; Hypoglycemic Agents; Insulin, Isophane; Insulin, Long-Acting; Male; Medicare; Retrospective Studies; United States

Topics: Diabetes Mellitus, Type 2; Drug Costs; Humans; Hypoglycemic Agents; Insulin; Insulin, Isophane

Ketosis prone type 2 diabetes (KPD) is presently a well-defined clinical entity, characterized by a debut with severe hyperglycemia and ketoacidosis similar to the presenting form of Type 1 diabetes mellitus (DM1). However, it appears in subjects with Type 2 diabetes mellitus (DM2) phenotype. This situation is caused by an acute, reversible dysfunction of the beta cell in individuals with insulin resistance. Once the acute stage subsides, patients behave as having a DM2 and do not require insulin treatment. They should be kept on a diet and oral hypoglycemic drugs due to their susceptibility to have recurrent acute ketotic decompensations.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Humans; Insulin, Isophane; Insulin, Short-Acting; Male; Middle Aged

To identify the baseline factors associated with achievement of glycosylated haemoglobin A1c (HbA1c) < 7.0% in Chinese patients receiving biphasic insulin as part 30 (BIAsp 30), who were previously inadequately controlled with oral anti-diabetic drugs (OADs).. A1 chieve was a multinational, prospective, open-label, 24-week non-interventional study in patients with type 2 diabetes initiating insulin analogues in 28 countries. The patients were enrolled to take BIAsp 30 according to physician's clinical judgments, who was also responsible for the treatment regimen and dosage adjustment. Primary safety endpoints were the incidence of serious drug adverse reactions (SADRs) including serious hypoglycaemia. Major efficacy endpoints were change in HbA1c, fasting plasma glucose (FPG), 2h post-prandial plasma glucose (2 hPG) from baseline. Relationships between baseline predictive baseline factors and achievement of HbA1c < 7.0% after treatment were examined using multivariate analysis.. In China, 4 100 patients initiated BIAsp 30 [54.2% males, age (56.2 ± 13.6) years]. No SADRs were reported. Mean HbA1c was reduced from (9.3 ± 2.1)% to (7.0 ± 1.0)%; FPG was reduced from (10.2 ± 3.3) mmol/L to (6.8 ± 1.3) mmol/L. Changes in 2 hPG after breakfast, lunch and dinner were (-5.6 ± 4.7), (-4.9 ± 4.3) and (-4.2 ± 4.1) mmol/L, respectively (all P < 0.001). The proportion of patients achieving HbA1c < 7.0% increased from 9.7% at baseline to 54.2% at week 24. Multivariate analysis revealed a negative relationship between baseline HbA1c, FPG, 2 hPG and HbA1c < 7.0% after treatment.. In the Chinese subgroup of the A1 chieve study, lower baseline HbA1c, FPG, 2 hPG were predictive factors for achieving HbA1c < 7.0% after 24-week treatment of BIAsp 30, indicating that the earlier initiation of BIAsp 30 in patients poorly controlled with OADs, the more helpful for them to achieve treatment target.

Topics: Administration, Oral; Asian People; Biphasic Insulins; Blood Glucose; China; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Male; Prospective Studies

Despite their reported benefits in terms of glycaemic control, insulin analogues are expensive for patients in developing countries. This study in Jordan aimed to compare the effectiveness and adverse events of premixed human insulin (BHI30) versus premixed insulin analogue (BIAsp30) in patients with type 2 diabetes. In a retrospective cohort study from October 2012 to March 2013, outcomes (HbA1c, weight, hypoglycaemia and lipohypertrophy) were compared at baseline and 6 months after treatment in 628 patients. BHI30 produced a significantly greater reduction in HbA1c than did BIAsp30. This difference in HbA1c remained significant after controlling for the effects of age, sex, duration of diabetes, body mass index and hypoglycaemia (β-coefficient was -0.18 in favour of BHI30). Weight gain and mild hypoglycaemia was significantly higher with BHI30 than with BIAsp30. BHI30 achieved better reduction in HbA1c compared with BIAsp30, with less cost, slightly more weight gain and greater reported mild hypoglycaemia.. هل تعتبر نظائر الإنسولين ضرورة لا مفر منها لمعالجة السكري من النمط 2 في البلدان النامية؟ حالة الأردن.. دانا حياصات، نزهت الشكرجي، هاشم جدوع، محمد لصوي، محمد الخطيب، كامل العجلوني.. برف النظر عن الفوائد المعروفة عن نظائر الإنسولين من حيث ضبط سكر الدم فإنها تعتر باهظة الثمن بالنسبة للمرضى في البلدان النامية. وقد هدفت هذه الدراسة التي أجريَت في الأردن إلى مقارنة الفاعلية والمضاعفات بن الإنسولين البري مسبق المزج (BHI30) ونظائر الإنسولين مسبق المزج (BIAsp30) لدى المرضى المصابن بالسكري من النمط 2. ففي دراسة أترابية استعادية - من أكتوبر/تشرين الأول 2012 إلى مارس/آذار 2013 - تمت مقارنة نتائج قياسات (HbA1c والوزن ونقص سكر الدم وتضخم الدهون عند بداية الدراسة وبعد 6 أشهر من معالجة 628 مريضاً. فنتج عن استخدام BHI30 انخفاض في HbA1c أكر بكثير مما نتج عن BIAsp30. وبقي هذا الفارق في HbA1c كبراً بعد ضبط تأثرات العمر والجنس ومدة الإصابة بالسكري ومؤشر كتلة الجسم ونقص سكر الدم (كان معامل- بيتا 0.18 لصالح BHI30) . وزيادة قليلة للوزن والانخفاض الطفيف لسكر الدم باستعمال BHI30 أعى بكثر مما كان عليه باستعمال BIAsp30 الفرق ذا دلالة إحصائية. لقد حقق BHI30 تخفيضاً أفضل ل HbA1c مقارنة مع BIAsp30 ، مع تكلفة أقل، وزيادة قليلة للوزن، بالإضافة إلى زيادة في إباغ المرضى عن الانخفاض الطفيف في سكر الدم.. Les analogues de l’insuline sont-ils une nécessité inévitable pour le traitement du diabète de type 2 dans les pays en développement ? Le cas de la Jordanie.. En dépit des avantages rapportés en termes de contrôle de la glycémie, les analogues de l’insuline sont coûteux pour les patients des pays en développement. La présente étude en Jordanie visait à comparer l’efficacité de l’insuline humaine prémélangée (BHI30) à celle de l’analogue de l’insuline prémélangé (BIAsp30) ainsi que les événements indésirables pour deux substances chez des patients atteints de diabète de type 2. Dans une étude de cohorte rétrospective menée d’octobre 2012 à mars 2013, les résultats (l’hémoglobine glycosylée1c, le poids, l’hypoglycémie et la lipohypertrophie) ont été comparés au début de l’étude, puis six mois après le traitement chez 628 patients. Le traitement par BHI30 a entraîné une réduction très supérieure de l'HbA1c par rapport au BIAsp30. Cette différence dans le taux d'HbA1c est restée importante après la correction pour les effets de l’âge, du sexe du patient et de la durée du diabète, de l’indice de masse corporelle et de l’hypoglycémie (le coefficient-β était de – 0,18 en faveur du BHI30). La prise de poids et l’hypoglycémie légère étaient nettement supérieures sous BHI30 que sous BIAsp30. Le traitement par BHI30 a permis une réduction plus importante de l’HbA1c par rapport au traitement par BIAsp30, à un coût moindre, avec une prise de poids légèrement supérieure et un taux d’hypoglycémie légère plus important.

Topics: Aged; Biphasic Insulins; Developing Countries; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Jordan; Male; Middle Aged; Retrospective Studies; Treatment Outcome

Biphasic insulin aspart 30 allows fewer daily injections versus basal-bolus insulin regimens, which may improve adherence and treatment outcome. This sub-analysis of the observational A1chieve study assessed clinical safety and effectiveness of biphasic insulin aspart 30 in people with type 2 diabetes previously receiving basal-bolus insulin regimens.. A1chieve was an international, open-label, 24-week study in people with type 2 diabetes starting/switching to biphasic insulin aspart 30, insulin detemir or insulin aspart. This sub-analysis assessed patients switching from insulin glargine- or neutral protamine Hagedorn insulin-based basal-bolus insulin regimens to biphasic insulin aspart 30.. 1024 patients were included. At 24 weeks, glycated haemoglobin and fasting plasma glucose were significantly reduced from baseline in both cohorts (all p<0.001). The proportion reporting any hypoglycaemia, major hypoglycaemia or nocturnal hypoglycaemia was significantly reduced after 24 weeks (all p<0.05). No serious adverse drug reactions were reported. Both cohorts had significantly improved health-related quality of life (HRQoL; p<0.001).. 24 weeks after switching from basal-bolus insulin regimens to biphasic insulin aspart 30, glycaemic control and HRQoL were significantly improved, and hypoglycaemia was significantly reduced. This suggests that people with type 2 diabetes inadequately controlled on basal-bolus insulin regimens can consider biphasic insulin aspart 30.

Topics: Adult; Africa, Northern; Aged; Asia; Biomarkers; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Substitution; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections; Insulin Aspart; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Latin America; Male; Middle Aged; Middle East; Quality of Life; Russia; Time Factors; Treatment Outcome

The aim was to observe the effects of switching from neutral protamine Hagedorn (NPH) insulin to insulin glargine on glycaemic control in patients with type 2 diabetes mellitus (T2DM) in everyday clinical practice in Italy. This multicenter, observational, retrospective study included 1,011 patients with T2DM who switched from NPH insulin to glargine or were maintained on NPH insulin. The primary outcome was change in HbA1c over 4-8 months. Secondary outcomes included fasting blood glucose (FBG), insulin dose, and hypoglycaemia. The intention-to-treat population consisted of 996 patients (glargine 496; NPH 500). Prior to switching, HbA1c was higher in the glargine than the NPH group [mean (±SD) 8.8 ± 1.4 vs. 7.9 ± 1.2%; p < 0.001]. HbA1c decreased after 4-8 months with glargine (8.2 ± 1.4%; p < 0.001) but not with NPH (8.0 ± 1.4%; p = 0.20). Similar results were observed for FBG. The daily dose of glargine increased from 0.22 ± 0.10 U/kg at the switch to 0.26 ± 0.11 U/kg at study end, while the NPH dose remained stable (0.19 ± 0.09-0.20 ± 0.09 U/kg). While not statistically significant, the percentage of patients with hypoglycaemic episodes during the last month of treatment tended to be less with glargine. No significant change in body weight occurred in either group. Switching patients from NPH insulin to insulin glargine in a real-life setting was associated with significant improvement in glycaemic control. The increase in glargine dose was not accompanied by increased hypoglycaemia or weight gain.

Topics: Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Italy; Male; Retrospective Studies

We performed a comparative analysis of the use of long-acting insulin (analogues) neutral protamine hagedorn (NPH), detemir (Det) and glargine (Gla), and quantified injection frequencies and daily insulin doses in patients with type 1 and 2 diabetes in daily practice.. A total number of 51 964 patients from 336 centres in Germany and Austria with type 1 and 2 diabetes with exclusive insulin therapy were retrospectively analysed.. A total number of 42.1%/75.9% (type 1/type 2) of patients used NPH, 19.9%/6.7% Det and 38.0%/17.4% Gla, with similar glycaemic control and proportion of severe hypoglycaemia for NPH/Det/Gla in type 1 (Mean HbA(1c) 7.98%/7.98%/8.07%; mean proportion of severe hypoglycaemia 11.06%/11.93%/10.86%) and type 2 diabetes (Mean HbA(1c) 7.61%/7.78%/7.61%; mean proportion of severe hypoglycaemia 5.66%/4.48%/5.03%). In type 1 diabetes, the mean daily injection frequencies of NPH versus Det versus Gla were 1.9 vs 1.8 vs 1.1, and total daily insulin injections were 5.3 vs 5.6 vs 5.0. The adjusted mean daily basal insulin doses were 0.36, 0.39 and 0.31 IU/kg, mean daily total insulin dose was lowest for Gla (0.74 IU/kg), followed by NPH (0.76 IU/kg) and Det (0.81 IU/kg). In type 2 diabetes patients, mean daily injection frequencies were 1.6 for NPH, 1.4 for Det and 1.1 for Gla, total daily insulin injections were 4.0 vs 4.1 vs 3.6. The mean daily basal insulin dosages were 0.30 IU/kg (NPH), 0.33 IU/kg (Det) and 0.29 IU/kg (Gla), mean total insulin doses per day were 0.63 IU/kg (NPH), 0.77 IU/kg (Det) and 0.67 IU/kg (Gla).. In a 'real-world' setting, the injection frequencies and doses of basal and total insulin per day are lowest with the use of insulin glargine compared with NPH-insulin or insulin detemir at similar glycaemic control and rates of severe hypoglycaemia.

Topics: Adult; Aged; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Retrospective Studies

The effectiveness and safety of initiating biphasic insulin aspart 30 in patients who were poorly controlled on oral glucose-lowering drugs were studied in randomized controlled trials, while results from clinical practice remain limited. This subgroup analysis was to provide such findings from a large-scale non-interventional study.. A1chieve was a multinational, prospective, open-label, non-interventional, 24-week study in patients with type 2 diabetes initiating insulin analogues in 28 countries across Asia, Africa, Europe, and Latin America. After physician had taken the decision to use this insulin, any patient with type 2 diabetes who was not treated with or who had started the study insulin within 4 weeks before inclusion was eligible. Patients were treated with study insulin alone or in combination with oral glucose-lowering drugs. Data on adverse drug reactions, hypoglycemia and glycemic control were collected at baseline, week 12 and 24. This is a report of a Chinese subgroup analysis from the A1chieve study.. Totally, 4 100 patients constituted this subgroup. No serious adverse drug reactions were reported. Rates of total, major, nocturnal hypoglycemic events (events/patient per year) were 1.47, 0.10, 0.31 at baseline and 1.35, 0.00, 0.22 at week 24, respectively. Glycemic control was improved as measured by hemoglobin A1c (mean 9.3% to 7.0%, reduction -2.3%), fasting plasma glucose (mean 10.2 to 6.8 mmol/L, reduction -3.5 mmol/L) and postprandial plasma glucose (mean 14.4 to 8.8 mmol/L, reduction -5.6 mmol/L), all P < 0.001. Change in mean body weight was +0.3 kg (P < 0.001).. In this subgroup analysis of the A1chieve study, biphasic insulin aspart 30 improved glycemic control with low risk of hypoglycemia.

Topics: Administration, Oral; Adult; Aged; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Prospective Studies

The 24-week, international, non-interventional A1 chieve study aimed to evaluate the safety and efficacy of insulin analogues in type 2 diabetes (T2D) in different countries. This sub-analysis reports results for T2D patients who switched from either biphasic human insulin (BHI) or human neutral protamine Hagedorn (NPH) insulin to biphasic insulin aspart 30 (BIAsp 30) in the Gulf cohort.. Gulf patients with T2D who switched to BIAsp 30 from either BHI or NPH insulin were included. Safety and efficacy measurements were made by the physicians as part of routine clinical care.. A total of 1486 patients switched from BHI to BIAsp 30 (BIP group) and 232 patients switched from NPH insulin to BIAsp 30 (NEU group). Baseline glycated haemoglobin A1c (HbA₁c ) was poor in patients in the BIP and NEU groups (mean value ± SD: 9.4 ± 1.8% and 9.7 ± 1.5%, respectively). Significant reductions in the proportion of patients reporting hypoglycaemia (overall, major, minor and nocturnal) were noted in the BIP group after 24 weeks of BIAsp 30 therapy (p < 0.001). No major hypoglycaemic events were reported at Week 24 in the NEU group. In both groups, the mean HbA1c , fasting plasma glucose and postprandial plasma glucose improved significantly after 24 weeks of BIAsp 30 therapy (p < 0.001). The mean body weight, lipid parameters and systolic blood pressure also improved significantly in both groups (p < 0.05).. BIAsp 30 therapy enhanced glycaemic control over 24 weeks and was well-tolerated in T2D patients poorly controlled on prestudy BHI or NPH insulin.

Topics: Bahrain; Biphasic Insulins; Diabetes Mellitus, Type 2; Drug Substitution; Female; Humans; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Kuwait; Male; Oman; Qatar; Quality of Life; Risk Assessment; Risk Factors; Saudi Arabia; Time Factors; Treatment Outcome; United Arab Emirates; Yemen

Topics: Child; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Injections, Intramuscular; Injections, Subcutaneous; Insulin, Lente

In a previous study, we showed early insulin therapy could improve β-cell function in type 2 diabetic patients. However, the molecular mechanism was not clear. In the present study, we addressed this question by analyzing the pancreatic microvasculature in diabetic rats after insulin treatment.. Diabetes was induced in rats by a combination of low dose streptozotocin (STZ; 40 mg/kg) and feeding of a high-fat diet. After the induction of diabetes, rats were treated with neutral protamine Hagedorn insulin (NPH; 6–8 U/day, s.c.) for 3 weeks. Three days after the end of treatment, rats were subjected to an intraperitoneal glucose tolerance test (IPGTT). The pancreatic microvasculature and the amount and size of the islets were evaluated by immunohistochemistry. Western blot analysis was used to determine levels of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGF-R2) protein.. Treatment with NPH improved insulin secretion from β-cells during the IPGTT and increased pancreatic islet size. The density of the microvasculature in the pancreas was determined by quantification of CD31, a marker of endothelial cells. Insulin treatment increased CD31 protein levels, as well as the expression of VEGF and VEGFR2.. The results suggest that insulin treatment improves islet recovery by increasing angiogenesis in the pancreas. The mechanism is related to the induction of VEGF and VEGFR2 expression in diabetic rats.

Topics: Animals; Blood Glucose; Blood Vessels; Blotting, Western; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diet, High-Fat; Glucose Tolerance Test; Hypoglycemic Agents; Immunohistochemistry; Insulin-Secreting Cells; Insulin, Isophane; Islets of Langerhans; Male; Platelet Endothelial Cell Adhesion Molecule-1; Rats; Rats, Sprague-Dawley; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2

Long-acting insulin analogues were developed to facilitate consistent glycemic control without excessive hypoglycemia. However, structural modifications of the insulin molecule can alter biological responses and binding characteristics with specific receptors. The aim of this study was to estimate the risk of sight-threatening diabetic retinopathy (STDR) associated with treatment using long-acting insulin analogues compared with intermediate-acting insulin in patients with type 2 diabetes mellitus (T2DM).. A retrospective cohort consisting of patients with T2DM aged 20 years of age and older with newly initiated treatment with long-acting insulin analogues (glargine and detemir) and intermediate-acting human insulin was identified from the National Health Insurance database between January 2004 and December 2006 and was subdivided into different cohorts. The risk of the development of STDR was determined by Cox regression models and compared between different cohorts.. Of the 46,739 eligible patients, initiators of insulin glargine, insulin detemir, and neutral protamine Hagedorn (NPH) insulin were identified for comparison using propensity-score matching methods. Long-acting insulin analogues were not associated with changed risk for STDR by intention-to-treat and time-varying use approaches between either matched or unmatched cohorts.. The strategies that aim at preventing diabetic retinopathy by treating T2DM patients with long-acting insulin analogues remain further prospective studies with longer follow-up period to validate our observations within an appropriate dosage range and to further evaluate the safety of long-acting insulin analogues on reducing the progression of diabetic retinopathy.

Topics: Adult; Aged; Aged, 80 and over; Blood Glucose; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Disease Progression; Female; Humans; Hypoglycemic Agents; Incidence; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Propensity Score; Retrospective Studies; Taiwan; Young Adult

This study aimed to assess the cost-effectiveness of starting insulin therapy with biphasic insulin aspart 30 (BIAsp 30) in people with type 2 diabetes inadequately controlled on oral glucose-lowering drugs in Saudi Arabia, India, Indonesia, and Algeria.. The IMS CORE Diabetes Model was used to evaluate economic outcomes associated with starting BIAsp 30, using baseline characteristics and treatment outcomes from the A(1)chieve study. Time horizons of 1 and 30 years were applied, with country-specific costs for complications, therapies, and background mortality. Incremental cost-effectiveness ratios (ICERs) are expressed as cost per quality-adjusted life-year (QALY) in local currencies, USD, and fractions of local GDP per capita (GDPc). Cost-effectiveness was pre-defined using the World Health Organization definition of <3.0 times GDPc. Comprehensive sensitivity analyses were performed.. In the primary 30-year analyses, starting BIAsp 30 was associated with a projected increase in life expectancy of >1 year and was highly cost-effective, with ICERs of -0.03 (Saudi Arabia), 0.25 (India), 0.48 (India), 0.47 (Indonesia), and 0.46 (Algeria) GDPc/QALY. The relative risk of developing selected complications was reduced in all countries. Sensitivity analyses including cost of self-monitoring, treatment costs, and deterioration of glucose control with time showed the results to be robust. In a 1-year analysis, ICER per QALY gained was still cost-effective or highly cost-effective.. Starting BIAsp 30 in people with type 2 diabetes in the A(1)chieve study was found to be cost-effective across all country settings at 1- and 30-year time horizons, and usefully increased predicted life expectancy.

Topics: Adult; Aged; Algeria; Autoimmune Diseases; Biphasic Insulins; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Health Care Costs; Humans; Hypoglycemic Agents; India; Indonesia; Insulin Aspart; Insulin, Isophane; Life Expectancy; Male; Middle Aged; Quality-Adjusted Life Years; Saudi Arabia; Time Factors; Treatment Outcome

The management of type 2 diabetes mellitus in long-term care (LTC) settings can be complex as a result of age-related complications. Despite guideline recommendations, sliding scale insulin remains commonplace in the LTC setting and data on basal insulin use are lacking.. This retrospective study used medical chart data and the Minimum Data Set from elderly LTC facility patients who received basal insulin (insulin glargine, insulin detemir, or neutral protamine Hagedorn insulin) for the treatment of diabetes, to investigate the practice patterns and associated clinical outcomes.. A total of 2,096 elderly, insulin-treated patients in LTC were identified, with 59.5% of them (N=1,247) receiving basal insulin. Of these, more than 50% of patients received sliding scale insulin in co-administration with basal insulin. Despite its ease of use, insulin pen use was very low, at 14.6%. Significant differences were observed between the basal insulin groups for glycated hemoglobin level and dosing frequency. Hypoglycemia was uncommon -17.2% of patients experienced at least one event, and there was no significant difference in the prevalence of hypoglycemia between the groups.. These data suggest the underutilization of basal insulin in the LTC setting and worryingly high combinational use with sliding scale insulin. Differences in glycated hemoglobin and dosing frequencies between types of basal insulin warrant further comparative effectiveness studies.

Topics: Aged; Aged, 80 and over; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Drug Utilization; Female; Glycated Hemoglobin; Homes for the Aged; Humans; Hypoglycemia; Injections, Subcutaneous; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Nursing Homes; Practice Patterns, Physicians'; Retrospective Studies; Risk Factors

Topics: Aged; Autoantibodies; Autoimmune Diseases; Biphasic Insulins; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Resistance; Insulin, Isophane

Early initiation of insulin therapy has widely been associated with numerous benefits, including improved glycaemic control and reduced long-term risk of developing microvascular diseases. Biphasic insulins offer a convenient option for insulin initiation, addressing both basal and postprandial insulin requirements with one injection, making them relatively simple for patients to dose. Development of biphasic insulin aspart (BIAsp) has further offered improved postprandial glycaemic control and lower rates of nocturnal and major hypoglycaemia than biphasic human insulin.. The safety and efficacy of the 30/70 rapid-acting/intermediate-acting formulation of BIAsp (BIAsp 30) in patients with type 2 diabetes was examined in the IMPROVE study, a 26-week, international, observational trial. In this subanalysis, baseline clinical factors that predicted treatment success, defined as HbA1c <7% (<53 mmol/mol) without experiencing hypoglycaemia after 26 weeks on BIAsp 30 therapy, were assessed.. The composite endpoint was defined for 44,010 (77%) patients from the total cohort of 57,478, and 28,696 of these were included in the statistical examination. The results of the analysis suggest that those with lower baseline HbA1c of ≤8% (≤64 mmol/mol), shorter duration of diabetes at baseline (<5 years) and no incidence of major hypoglycaemia at 13 weeks, or minor hypoglycaemia at 4 weeks, before the beginning of the trial were more likely to achieve treatment success.. Lower baseline HbA1c, shorter duration of diabetes and no incidence of hypoglycaemia up to 13 weeks prior to initiation are predictors of achieving HbA1c <7% without hypoglycaemia with a BIAsp 30 regimen. These results suggest that it is easier to reach target without hypoglycaemia with BIAsp 30 when prescribed earlier. As this was an observational study, lack of control groups or randomisation, as well as varying clinical practices in study countries, potentially introduced bias.. ClinicalTrials.gov NCT00659282.

Topics: Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Treatment Outcome

To evaluate the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) in ASEAN type 2 diabetes (T2D) patients switched from biphasic human insulin (BHI) in the non-interventional 24-week A₁chieve study.. Indonesian, Malaysian, Filipino and Singaporean patients switched from BHI to BIAsp 30 at their physicians' discretion were included. The incidence of serious adverse drug reactions (SADRs), including major hypoglycaemia was the primary endpoint. Changes in hypoglycaemia, glycated haemoglobin A1c (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPPG), lipids, body weight and systolic blood pressure were also evaluated. Quality of life (QoL) was measured using the EQ-5D questionnaire.. For the 465 patients included (mean ± SD age: 56 ± 10.3 years, diabetes duration: 9.7 ± 7.1 years, baseline HbA1c: 9.4 ± 1.8%), the mean pre-study BHI dose was 0.62 ± 0.28 IU/kg and 63.4% were dosing BHI twice daily (bid). The mean baseline BIAsp 30 dose was 0.65 ± 0.27 U/kg, titrated up to 0.71 ± 0.28 U/kg over 24 weeks, and most patients continued bid dosing. No SADRs or major hypoglycaemic episodes were reported. The proportion of patients reporting overall hypoglycaemia decreased significantly from 10.8% at baseline to 3.4% at Week 24 (p < 0.0001). Significant improvements in glycaemic control were noted (HbA1c: -1.4 ± 1.7%, FPG: -56.7 ± 72.5 mg/dL, post-breakfast PPPG: -84.8 ± 82.8 mg/dL, p < 0.001). Mean QoL improved by +6.6 ± 14.6 points (p < 0.001).. BIAsp 30 was well-tolerated and significantly increased glycaemic control in this ASEAN subgroup poorly controlled on BHI.

Topics: Aged; Asia, Southeastern; Asian People; Biomarkers; Biphasic Insulins; Blood Glucose; Blood Pressure; Diabetes Mellitus, Type 2; Drug Combinations; Drug Substitution; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Lipids; Male; Middle Aged; Prevalence; Quality of Life; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Weight Gain

To determine the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) in the ASEAN cohort of the A₁chieve study.. Type 2 diabetes patients from Indonesia, Malaysia, Philippines and Singapore prescribed BIAsp 30 therapy were included. The primary outcome was evaluation of serious adverse drug reactions including major hypoglycaemia over 24 weeks. Secondary outcomes were changes in hypoglycaemic events, serious adverse events (SAEs) and effectiveness parameters.. This sub-analysis included 2798 patients (insulin-naive, 1903; insulin-experienced, 895) with mean age ± SD, 55.3 ± 10.8 years, BMI, 24.9 ± 4.6 kg/m(2) and diabetes duration, 7.5 ± 5.9 years. Baseline HbA1c in the entire cohort was poor (9.9%, 85 mmol/mol). A total of 15 SAEs were reported in 7 insulin-experienced patients (1 moderate event was related to BIAsp 30). Overall hypoglycaemia at Week 24 was 0.88 events/patient-year compared to 1.71 events/patient-year reported at baseline (change in proportion of patients affected, p < 0.0001). No major hypoglycaemia was reported at Week 24. BIAsp 30 significantly improved glucose control (HbA1c, fasting plasma glucose and postprandial plasma glucose, p < 0.001) at Week 24. The proportion of patients achieving HbA1c <7.0% at Week 24 was 35.3% compared to 3.5% at baseline. The lipid profile and systolic blood pressure also improved significantly (p < 0.001). Quality of life was positively impacted (mean change in visual analogue scores from EQ-5D = 10.6 ± 13.8 points, p < 0.001).. BIAsp 30 was well-tolerated and improved glucose control while decreasing the risk of hypoglycaemia.

Topics: Adult; Aged; Asia, Southeastern; Asian People; Biomarkers; Biphasic Insulins; Blood Glucose; Blood Pressure; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Lipids; Male; Middle Aged; Prevalence; Quality of Life; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Weight Gain

To determine the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) therapy in Bangladeshi type 2 diabetes (T2D) patients switched from biphasic human insulin (BHI) as a sub-analysis of the A₁chieve study.. Bangladeshi patients switched from BHI to BIAsp 30 at the discretion of their physicians were included. The primary outcome was the incidence of serious adverse drug reactions (SADRs), including major hypoglycaemia. Secondary outcomes comprised changes from baseline to Week 24 in the number of hypoglycaemic events, glycated haemoglobin A1c (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPPG), systolic blood pressure and body weight. Quality of life (QoL) was evaluated at baseline and Week 24 using the EQ-5D questionnaire.. A total of 82 patients (mean age ± SD: 52.3 ± 12.2 years; body mass index: 25.6 ± 3.3 kg/m(2)) with a mean diabetes duration of 9.5 ± 5.5 years and mean duration on insulin of 2.5 ± 2.4 years were included. The mean BIAsp 30 dose was 0.49 ± 0.20 U/kg at baseline and 0.47 ± 0.17 U/kg at Week 24. No SADRs were reported. No events of hypoglycaemia (overall, major, minor or nocturnal) were reported at Week 24. Mean HbA1c, FPG and PPPG levels improved by -2.5 ± 1.3%, -65.0 ± 31.8 mg/dL and -119.3 ± 48.7 mg/dL, respectively, over 24 weeks. QoL also improved (mean change from baseline: +28.5 ± 12.9 points).. Switching from BHI to BIAsp 30 therapy improved blood glucose control and was well-tolerated in this Bangladeshi subgroup.

Topics: Adult; Asian People; Bangladesh; Biomarkers; Biphasic Insulins; Blood Glucose; Blood Pressure; Diabetes Mellitus, Type 2; Drug Combinations; Drug Substitution; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Lipids; Male; Middle Aged; Prevalence; Prospective Studies; Quality of Life; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Weight Gain

To evaluate the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) in Indonesian type 2 diabetes patients switched from biphasic human insulin 30 (BHI 30) as a sub-analysis of the A₁chieve study.. Clinical safety and effectiveness over 24 weeks was evaluated in Indonesian patients who switched from BHI 30 to BIAsp 30 at the discretion of their physician.. A total of 244 patients with mean age ± SD 55.6 ± 9.5 years, BMI 24.6 ± 3.8 kg/m(2), and mean diabetes duration 7.8 ± 5.7 years were included. The mean pre-study BHI 30 dose was 0.56 ± 0.25 IU/kg and the baseline BIAsp 30 dose was 0.60 ± 0.26 U/kg titrated up to 0.65 ± 0.25 U/kg by Week 24. No serious adverse drug reactions were reported throughout the study. Overall hypoglycaemia decreased from 2.18 to 0.06 events/patient-year with a significant decrease in the proportion of patients affected (p < 0.0001). No nocturnal or major hypoglycaemia was reported at Week 24. HbA1c improved from 8.8 ± 1.2% at baseline to 7.3 ± 0.8% at Week 24. A total of 45 patients achieved HbA1c <7.0% as compared to 5 patients with HbA1c <7.0% at baseline. FPG and PPPG improved significantly after 24 weeks (p < 0.001). Quality of life was positively impacted (change in visual analogue scores, 3.0 ± 11.6 points, p < 0.001).. Switching from BHI 30 to BIAsp 30 in this Indonesian cohort was well-tolerated and improved glycaemic control with a decreased risk of hypoglycaemia.

Topics: Aged; Asian People; Biomarkers; Biphasic Insulins; Blood Glucose; Blood Pressure; Diabetes Mellitus, Type 2; Drug Combinations; Drug Substitution; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Indonesia; Insulin Aspart; Insulin, Isophane; Lipids; Male; Middle Aged; Prevalence; Quality of Life; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Weight Gain

To evaluate the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) in Filipino patients with type 2 diabetes previously treated with biphasic human insulin 30 (BHI 30).. Safety and effectiveness outcomes were measured in all patients switching from BHI 30 to BIAsp 30 in the Filipino cohort of the 24-week, multinational, prospective, non-interventional A₁chieve study.. A total of 111 Filipino patients (mean age ± SD, 57.4 ± 12.8 years; BMI, 25.8 ± 5.6 kg/m(2)) with mean diabetes duration of 9.9 ± 7.1 years switched therapy from BHI 30 to BIAsp 30. The mean pre-study BHI 30 dose was 0.65 ± 0.28 IU/kg and the baseline BIAsp 30 dose was 0.65 ± 0.26 U/kg titrated up to 0.70 ± 0.26 U/kg by Week 24. No serious adverse drug reactions were reported. Overall hypoglycaemia was reduced from 5.62 to 1.98 events/patient-year. Minor and nocturnal hypoglycaemia decreased and no major hypoglycaemia was reported at Week 24. Glucose control improved from baseline to Week 24 (HbA1c, -2.2 ± 2.1% [24 ± 23 mmol/mol]; FPG, -72.0 ± 71.8 mg/dL; PPPG, -145.5 ± 125.4 mg/dL). A total of 24 patients achieved HbA1c levels <7.0% at Week 24 compared to 6 patients reporting this target at baseline. Quality of life was positively impacted at Week 24 (change in visual analogue scores, 15.3 ± 16.9 points).. Switching from BHI 30 to BIAsp 30 improved glycaemic control without increasing the risk of hypoglycaemia.

Topics: Aged; Asian People; Biomarkers; Biphasic Insulins; Blood Glucose; Blood Pressure; Diabetes Mellitus, Type 2; Drug Combinations; Drug Substitution; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Lipids; Male; Middle Aged; Philippines; Prevalence; Quality of Life; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Weight Gain

To evaluate the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) in Indonesian patients with type 2 diabetes (T2D) as part of the 24-week, international, prospective, non-interventional A₁chieve study.. Indonesian patients who started BIAsp 30 were included. Safety and efficacy was measured as part of routine clinical practice at baseline, Week 12 and Week 24.. Overall, 1324 patients having a mean ± SD age, duration of diabetes and body mass index of 55.2 ± 9.9 yrs, 6.8 ± 5.2 yrs and 24.1 ± 3.6 kg/m(2), respectively, were enrolled. 67% of patients were insulin-naive and 33% were prior insulin users. Glycaemic control was poor at baseline. After 24 weeks, significant reductions from baseline were observed in the mean glycated haemoglobin A1c (HbA1c) (-2.6%), fasting plasma glucose (-93.8 mg/dL) and postprandial plasma glucose (-134.8 mg/dL) levels in the entire cohort (p < 0.001). Significant reductions were also seen in insulin-naive patients and prior insulin users. At Week 24, 29.9% of patients in the entire cohort achieved target HbA1c level of <7.0%, while 26.7% and 39.2% achieved this target among insulin-naive patients and prior insulin users, respectively. The proportion of patients reporting overall hypoglycaemia significantly decreased in the entire cohort after 24 weeks of BIAsp 30 therapy. A small significant increase in body weight was noted in the entire cohort, insulin-naive patients and prior insulin users.. The current study suggests that BIAsp 30 can be considered as a safe and effective option for initiating as well as intensifying insulin therapy in Indonesian patients with T2D.

Topics: Adult; Aged; Asian People; Biomarkers; Biphasic Insulins; Blood Glucose; Blood Pressure; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Indonesia; Insulin Aspart; Insulin, Isophane; Lipids; Male; Middle Aged; Prevalence; Prospective Studies; Quality of Life; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Weight Gain

To add to the evidence on comparative long-term effects of insulin analog glargine versus human NPH insulin on the risk for cancer.. We identified cohorts of initiators of glargine and human NPH without an insulin prescription during the prior 19 months among patients covered by the Inovalon Medical Outcomes Research for Effectiveness and Economics Registry (MORE2 Registry) between January 2003 and December 2010. Patients were required to have a second prescription of the same insulin within 180 days and to be free of cancer. We balanced cohorts on risk factors for cancer outcomes based on comorbidities, comedication, and health care use during the prior 12 months using inverse probability of treatment weighting. Incident cancer was defined as having two claims for cancer (any cancer) or the same cancer (breast, prostate, colon) within 2 months. We estimated adjusted hazard ratios (HRs) and their 95% CI using weighted Cox models censoring for stopping, switching, or augmenting insulin treatment, end of enrollment, and mortality.. More patients initiated glargine (43,306) than NPH (9,147). Initiators of glargine (NPH) were followed for 1.2 (1.1) years and 50,548 (10,011) person-years; 993 (178) developed cancer. The overall HR was 1.12 (95% CI 0.95-1.32). Results were consistent for breast cancer, prostate cancer, and colon cancer; various durations of treatment; and sensitivity analyses.. Patients initiating insulin glargine rather than NPH do not seem to be at an increased risk for cancer. While our study contributes significantly to our evidence base for long-term effects, this evidence is very limited mainly based on actual dynamics in insulin prescribing.

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Incidence; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Insulin, Regular, Human; Isophane Insulin, Human; Male; Middle Aged; Neoplasms; Probability; Proportional Hazards Models; Registries; Risk Factors

To determine the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) in Algerian patients with type 2 diabetes initiating insulin or switching from prior insulin therapy.. Insulin-naive and insulin-experienced patients, including prior basal insulin users, starting BIAsp 30 were evaluated in this sub-analysis of the 24-week, open-label, non-interventional A₁chieve study. Clinical safety and effectiveness was evaluated as a part of routine clinical care.. A total of 134 insulin-naive patients initiating BIAsp 30 at a mean dose of 0.44 ± 0.23 U/kg and 283 insulin-experienced patients, including 129 prior basal insulin users, switching from a mean pre-study insulin dose of 0.51 ± 0.23 U/kg to BIAsp 30 (0.54 ± 0.20 U/kg) were evaluated. At Week 24, the average BIAsp 30 dose was 0.60 ± 0.25 U/kg and 0.66 ± 0.24 U/kg in insulin-naive and insulin-experienced patients, respectively. No serious adverse drug reactions were reported. From baseline to Week 24, the proportion of patients experiencing overall hypoglycaemia increased in the insulin-naive group (p = 0.0067) and no significant changes were reported in the insulin-experienced group including prior basal insulin users. Glucose control improved significantly in the insulin-experienced group (p < 0.001) and appeared to improve in the insulin-naive patients and prior basal insulin users as well. Body weight increased significantly in all patients (p < 0.001). Quality of life was positively impacted after 24 weeks of BIAsp 30 therapy.. Initiating or switching to BIAsp 30 therapy in this Algerian cohort was well-tolerated and significantly improved glucose control.

Topics: Algeria; Biomarkers; Biphasic Insulins; Blood Glucose; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Lipids; Male; Middle Aged; Practice Patterns, Physicians'; Prospective Studies; Quality of Life; Risk Factors; Treatment Outcome; Weight Gain

To examine the criteria that may influence physicians' choice of starting insulin in type 2 diabetes patients in routine practice in Algeria as a sub-analysis of the A₁chieve study.. A₁chieve was a 24-week international, prospective, non-interventional study conducted to evaluate the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30), insulin detemir (IDet), or insulin aspart alone or in combination, in real-life clinical settings. We report an analysis of baseline data from insulin-naive patients initiating basal or premix insulin from the Algeria cohort (n = 1494). Demographic and anthropometric data, blood glucose control at inclusion, microvascular complications, and pre-study therapy was compared between the two groups.. A total of 772 insulin-naive patients initiating therapy with IDet or BIAsp 30 were included in this analysis: IDet: 638 (83%), BIAsp 30: 134 (17%). Most IDet-group patients initiated once-daily therapy (n = 636; 99.7%); conversely, most BIAsp 30-group patients started twice-daily therapy (n = 104; 77.6%). Baseline factors influencing regimen choice were microvascular complications (odds ratio [95% CI], yes/no: 0.73 [0.55, 0.98]; p = 0.034) and HbA1c at baseline (%, odds ratio [95% CI] 0.82 [0.72, 0.94]; p = 0.004).. In routine practice, physicians in Algeria are more likely to prescribe basal insulin at initiation of insulin therapy in type 2 diabetes. The prescription of a premix insulin therapy correlated with poor glycaemic control and the incidence of microvascular complications.

Topics: Algeria; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Postprandial Period; Practice Patterns, Physicians'; Prospective Studies; Treatment Outcome

Defects in both insulin secretion and function play a fundamental role in the pathophysiologic mechanisms underlying both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). As the most physiologic treatment option available, insulin plays a central role in the management of patients with T1DM and a growing role in the management of patients with T2DM, as is reflected in current treatment guidelines.

Topics: Chemistry, Pharmaceutical; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Insulin, Short-Acting; Insulins

Long-acting basal insulin analogs have demonstrated positive effects on the balance between effective glycemic control and risk of hypoglycemia versus neutral protamine Hagedorn (NPH) insulin in randomized controlled trials. Evidence of severe hypoglycemic risk with insulin detemir, insulin glargine, or NPH insulin is presented from a nationwide retrospective database study.. Data from hospital and secondary healthcare visits due to hypoglycemic coma from 75 682 insulin-naïve type 1 or 2 diabetes patients initiating therapy with NPH insulin, insulin glargine, or insulin detemir in Finland between 2000 and 2009 were analyzed. Incidence rates with 95% confidence intervals (CIs) were calculated using Poisson regression. Hazard ratios were estimated using Cox's regression with adjustments for relevant background variables.. The adjusted risk of hospital/secondary healthcare visits due to the first severe hypoglycemic event was 21.7% (95% CI 9.6-32.1%, p < 0.001) lower for insulin detemir and 9.9% (95% CI 1.5-17.6%, p = 0.022) lower for insulin glargine versus NPH insulin. Risk of hypoglycemic coma recurrence was 36.3% (95% CI 8.9-55.5%, p = 0.014) lower for detemir and 9.5% but not significantly (95% CI -10.2 to 25.7%, p = 0.318) lower for glargine versus NPH insulin. Risk of all hypoglycemic coma events was 30.8% (95% CI 16.2-42.8%, p-value <0.001) lower for detemir and 15.6% (95% CI 5.1-25.0%, p-value 0.005) lower for glargine versus NPH. Insulin detemir had a significantly lower risk for first (13.1% lower [p = 0.034]), recurrent (29.6% lower [p = 0.021]), and all (17.9% lower [p = 0.016]) severe hypoglycemic events than insulin glargine.. There were considerable differences in risk of hospitalization or secondary healthcare visits due to hypoglycemic coma between basal insulin treatments in real-life clinical practice.

Topics: Databases, Factual; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Coma; Female; Finland; Follow-Up Studies; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Medical Record Linkage; Poisson Distribution; Proportional Hazards Models; Randomized Controlled Trials as Topic; Retrospective Studies; Risk

The aim of A1chieve was to remedy the deficit of data on the efficacy and safety of insulin analogues in routine clinical care in less well-resourced developed countries. To present results from the Bangladesh cohort of the A1chieve study receiving BIAsp 30 ± oral anti diabetic drugs. A1chieve was a 6-month, observational study of 66,726 people with type 2 diabetes, started on insulin detemir, insulin aspart or biphasic insulin aspart (BIAsp 30) in 28 countries across four continents. A total of 1,093 subjects were recruited from 49 sites in Bangladesh and 580 subjects initiated on BIAsp 30 were studied. In the entire cohort, treatment with BIAsp 30 for 24 weeks significantly reduced mean HbA(1c) (2.8%, p < 0.001), fasting plasma glucose (4.0 mmol/L, p < 0.001) and post prandial plasma glucose (6.6 mmol/L, p < 0.001) levels from baseline. The rate of overall hypoglycaemic events in the entire cohort also reduced significantly at 24 weeks (1.86 to 0.02 events/person year, p < 0.0001). BIAsp 30 can be considered as a safe and effective option for initiating as well as intensifying insulin therapy for type 2 diabetes.

Topics: Adult; Bangladesh; Biphasic Insulins; Cohort Studies; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Treatment Outcome

Biphasic insulin aspart 30 (BIAsp 30) has been shown in randomised controlled trials and the IMPROVE™ observational study to reduce postprandial blood glucose (PPBG) - thought to be an independent risk factor for cardiovascular disease. We used multivariate regression analysis to identify predictors of PPBG reduction in the IMPROVE™ study. A total of 52,419 type 2 diabetes patients were enrolled in the IMPROVE™ study (pre-study therapy subgroups: no pharmaceutical therapy, n = 8966; oral antidiabetic drugs [OADs] only, n = 33,797; insulin ± OADs, n = 9568; missing information on pre-study therapy, n = 88). Mean change from baseline in PPBG (mean of three meals) in the global cohort was -6.3 mmol/L; reductions in subgroups were: no pharmaceutical therapy, -8.8 mmol/L; OADs only, -6.0 mmol/L; insulin ± OADs, -5.1 mmol/L. High baseline PPBG was consistently and strongly predictive of PPBG response; lower baseline HbA1c and body mass index, greater age and shorter diabetes duration were also significant predictors of PPBG change. The novel findings from this study indicate that most patients can be expected to achieve a PPBG response with BIAsp 30 irrespective of baseline characteristics or previous therapy with an expected larger PPBG reduction when baseline PPBG is higher.

Topics: Administration, Oral; Asia; Biomarkers; Biphasic Insulins; Blood Glucose; Canada; Diabetes Mellitus, Type 2; Drug Substitution; Europe; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Injections; Insulin Aspart; Insulin, Isophane; Multivariate Analysis; Postprandial Period; Treatment Outcome

Type 2 diabetes mellitus is characterized by hyperglycaemia. Incidence and progression of microvascular complications have been shown to undergo reduction with lowered glucose levels.. This is an open-label, non-randomized, non-interventional, observational study of safety and efficacy of BiAsp 30, enrolling 2223 patients with type 2 diabetes mellitus. Patients previously treated with oral antidiabetic drugs and/or human insulin were recruited, provided they had been hospitalized for at least 3 days. Data were collected during a single multi-stage visit lasting up to 6 days, during the patient's hospitalization period. A mild hypoglycaemic episode was defined as blood glucose measurement < 56 mg/dL (3.1 mmol/L). A severe hypoglycaemia was hypoglycaemic episode requiring assistance of another person.. The total number of hypoglycaemic episodes decreased over time of follow-up. The intensity of severe hypoglycaemic episodes decreased by almost a third from day to day (IRR = 0.64, 95%, p < 0.001). However, intensity of mild hypoglycaemic episodes was the same over the subsequent days of follow-up (IRR = 0.97, p > 0.1). Mean blood glucose concentration decreased from 202.0 mg/dL to 157.8 mg/dL after 3 days and to 138.3 mg/dL after 6 days (p < 0.001).. This study highlights the safety, efficacy and ease of initiation of insulin BiAsp 30 therapy for treatment of type 2 diabetes mellitus.

Topics: Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Male; Treatment Outcome

Allergy to insulin became a rare complication due to the introduction of recombinant human insulin preparations. Nevertheless, allergic reactions to components of such preparations can occur. We report a case of a 61-year-old man with an atopic background and affected by diabetes mellitus type 2 since 27 years, who experienced generalized allergy to insulin at the moment of switching oral anti-diabetics to insulin. Prick tests revealed an allergy specifically to zinc, and the patient was treated with zinc-free glulisine insulin. After 8 months of such treatment, patient's glucose is stable and he never experienced allergic reactions to insulin injections. Even insulin allergy due specifically to zinc is rare, such complication must be assessed especially in a patient suffering from multiple allergies.

Topics: Diabetes Mellitus, Type 2; Drug Hypersensitivity; Humans; Hypoglycemic Agents; Insulin; Insulin, Isophane; Male; Middle Aged; Zinc

This study compared the health and economic benefits of saxagliptin versus insulin as second-line therapy with either metformin (MET) or sulfonylurea (SU) after failure of the respective monotherapies for patients with type 2 diabetes in Poland.. The cost-effectiveness was assessed using a previously published diabetes model. Disease progression, utilities, and effects of changes in glycosylated hemoglobin (HbA1c), weight, and hypoglycemic events were taken from published studies, and Polish sources were used where possible.. MET + saxagliptin reduced severe hypoglycemic complications and weight versus MET + insulin, with an incremental benefit of 0.13 quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) of 27,454 Polish zloty (PLN) ($9,966 U.S.) per QALY gained. SU + saxagliptin showed an incremental benefit of 0.14 QALYs and ICER of 24,663 PLN ($8,953 U.S.) per QALY gained versus SU + insulin, with reduced incidence of symptomatic and severe hypoglycemias. Results were most sensitive to disutilities associated with weight gain, hypoglycemia, injection fear, HbA1c changes, threshold for switching treatment, and patients' age. Results were robust to various model assumptions and inputs. Using a willingness-to-pay threshold of 100,000 PLN ($36,300 U.S.) per QALY gained, the probability that saxagliptin is cost-effective in these analyses was 74% (MET) and 76% (SU).. Saxagliptin in combination with MET or SU is likely to represent a cost-effective treatment option in Polish patients with type 2 diabetes failing first-line treatment.

Topics: Adamantane; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Dipeptides; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin, Isophane; Male; Metformin; Middle Aged; Models, Economic; Poland; Quality-Adjusted Life Years; Sulfonylurea Compounds

In this rodent study, we compared the effects of early versus late intensive insulin therapy on diabetic nephropathy and potential causal mechanisms. Diabetes was induced in rats by high-fat diet and low-dose streptozotocin. Intensive insulin therapy was initiated in the early intensive insulin therapy groups as soon as diabetes was confirmed and lasted for 8 (8wEI group) and 16 weeks (16wEI group). In the late insulin therapy group (LI group), intensive insulin treatment was initiated 8 weeks later and lasted for 8 weeks. Age-matched diabetic rats (8wDM group and 16wDM group) and non-diabetic rats (8wNC group and 16wNC group) served as controls. Histological analysis, real-time PCR, and western blot were performed in renal cortex specimens. Glomerular hypertrophy and mesangial matrix expansion were prominent in the 16wDM and LI groups while the EI groups remained normal and similar to the 16wNC group. Western blots revealed that p38 MAPK activities in the EI groups decreased significantly, whereas the level in the LI group was markedly higher than the 16wEI group, and not different from the DM groups. Activities of MKK3/6, CREB and MKP-1 proteins as well as CREB and MKP-1 mRNA showed a similar pattern. Therefore, we concluded that early intensive insulin treatment and attainment of good glycemic control counteracted some renal molecular pathways associated with epigenetic metabolic memory to minimize risk of diabetic nephropathy. However, late insulin therapy did not abrogate the increased renal cortical p38 MAPK pathway activation in diabetic rats and led to glomerular hypertrophy and extracellular matrix expansion.

Topics: Animals; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Gene Expression Regulation; Glomerular Mesangium; Humans; Hypertrophy; Hypoglycemic Agents; Insulin, Isophane; Insulin, Regular, Human; Isophane Insulin, Human; Kidney Cortex; Kidney Glomerulus; Male; MAP Kinase Signaling System; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Protein Processing, Post-Translational; Random Allocation; Rats; Rats, Sprague-Dawley; RNA, Messenger; Time Factors

Data from a 20-week trial comparing insulin detemir and neutral protamine Hagedorn (NPH) insulin in insulin-naïve people with type 2 diabetes were analyzed using willingness-to-pay (WTP) data, a proxy for patient preference. The advantages of insulin detemir relative to NPH insulin with respect to a lower hypoglycemia rate and less weight gain were associated with a value of €27.87 per month.

Topics: Diabetes Mellitus, Type 2; Financing, Personal; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Outcome Assessment, Health Care; Patient Preference; Proxy; Sweden

To compare the persistence (treatment duration) of basal insulin supported oral therapy (BOT) using insulin glargine (GLA) or NPH insulin (NPH) in Type-2 diabetic patients.. This retrospective cohort study reports results from an analysis of claims data from prescriptions for ambulatory patients within the German Statutory Health Insurance scheme. The study is based on claims data from more than 80% of German community pharmacies. Treatment duration until switching to a basal bolus treatment regimen (intensified conventional insulin therapy: ICT) was determined in insulin-naïve patients who began treatment with BOT using GLA or NPH between 01/2003 and 12/2006.. A total of 97,998 patients (61,070 GLA and 36,928 NPH) were included. Within the observation period, 23.5% of GLA patients and 28.0% of NPH patients switched from BOT to ICT. The upper quartile of probability of continuation of therapy (the 75th percentile) was reached after 769 days in GLA patients and after 517 days in NPH patients. Therefore, the risk of switching to ICT was significantly higher with NPH compared to GLA: hazard ratios were 1.34 (99% CI: 1.29-1.38; unadjusted) and 1.22 (99% CI: 1.18-1.27) after adjustment for predefined covariates. Various sensitivity analyses using modified inclusion criteria and endpoint definitions were applied and these confirmed the initial results.. Type-2 diabetic patients under BOT with GLA stayed significantly longer on the initial therapy before switching to ICT than patients on BOT using NPH.

Topics: Administration, Oral; Cohort Studies; Databases, Factual; Diabetes Mellitus, Type 2; Germany; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Proportional Hazards Models; Retrospective Studies; Time Factors

We evaluated the effectiveness of insulin glargine (glargine)-based regimens in patients with type 2 diabetes mellitus (T2DM) in clinical practice in Spain.. This was a retrospective, registry-based study of 1482 patients treated with neutral protamine Hagedorn (NPH) who were either switched to glargine or maintained on NPH at investigators' discretion. The primary outcomes were HbA(1c) change over a period of 4-9 months follow-up and incidence of hypoglycaemia.. Prior to switching treatment, mean ± standard deviation HbA(1c) was worse in the glargine vs. the NPH group (8.3 ± 1.2% vs. 7.9 ± 1.1% respectively; p < 0.0001). After 4-9 months of treatment, mean reductions in HbA(1c) were greater with glargine vs. NPH (-1.0 ± 1.0% vs. -0.2 ± 0.8% respectively; p < 0.0001) and the incidence of hypoglycaemia in the month prior to the study visit was lower (21.8% vs. 47.6% respectively; p < 0.0001). An expected reduction in dosing frequency, as well as in the basal insulin dose was reported for glargine vs. NPH, with 97.3% of glargine-treated patients on once-daily injections and 81.2% on NPH receiving twice-daily therapy. Improvements in treatment satisfaction were significantly higher with glargine (p < 0.0001).. In a Spanish clinical practice setting, patients with T2DM who switched to glargine from NPH experienced significantly greater reductions in mean HbA(1c) and a lower incidence of hypoglycaemia than patients maintained on NPH.

Topics: Administration, Oral; Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Substitution; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Patient Satisfaction; Treatment Outcome

To evaluate the cost-effectiveness of insulin detemir vs. NPH insulin once daily, in patients with type 2 diabetes in the Swedish setting based on clinical data from a published randomized controlled trial.. Projections of long-term outcomes were made using the IMS CORE Diabetes Model (CDM), based on clinical data from a 26-week randomized controlled trial that compared once daily insulin detemir and NPH insulin, when used to intensify insulin treatment in 271 patients with type 2 diabetes and body mass index (BMI) 25-40 kg/m(2). Trial results showed that insulin detemir was associated with a significantly lower incidence of hypoglycemic events and significantly less weight gain in comparison with NPH insulin. The analysis was conducted from a third party payer perspective and the base case analysis was performed over a time horizon of 40 years and future costs and clinical outcomes were discounted at a rate of 3% per year.. Insulin detemir was associated with higher mean (SD) quality-adjusted life expectancy (5.42 [0.10] vs. 5.31 [0.10] quality-adjusted life years [QALYs]) and lower overall costs (SEK 378,539 [10,372] vs. SEK 384,216 [11,230]; EUR 33,794 and EUR 34,300, respectively, where 1 EUR=11.2015 SEK) compared with NPH insulin. Sensitivity analysis showed that the principal driver of the benefits associated with insulin detemir was the lower rate of hypoglycemic events (major and minor events) vs. NPH insulin, suggesting that detemir might also be cost-saving over a shorter time horizon. Limitations of the analysis include the use of data from a trial outside Sweden in the Swedish setting.. Based on clinical input data derived from a previously published randomized controlled trial, it is likely that in the Swedish setting insulin detemir would be cost-saving in comparison with NPH insulin for the treatment of patients with type 2 diabetes.

Topics: Adult; Aged; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Models, Theoretical; Outcome Assessment, Health Care; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Sweden; Treatment Outcome

To investigate the safety and efficacy of switching to biphasic insulin aspart (BIAsp) 30, 50 or 70 in patients with type 2 diabetes previously treated with biphasic human insulin (BHI) 30/50 (with or without oral glucose-lowering drugs) in routine clinical practice.. This was a 26-week, prospective, observational study conducted in Belgium and Luxembourg. Data were collected at baseline before patients switched and at 12 and 26 weeks after starting BIAsp 30, 50 or 70. Safety endpoints were incidence and rate of hypoglycemia (major, minor, nocturnal), adverse events and body-weight changes. Efficacy assessments included HbA(1c) and 7-point self-measured plasma glucose (PG) profiles. Changes from baseline were analyzed using paired t-tests.. Of 592 patients analyzed, 72% switched to twice-daily BIAsp and 20% to three-times daily BIAsp. Upon switching, 27% of patients received intensified treatment (i.e., more daily doses than with their previous BHI). At all three data-collection points, approximately two-thirds of patients were taking BIAsp 30 and approximately one-third were taking BIAsp 50; very few patients took BIAsp 70. Mean total daily insulin dose increased significantly from baseline (51.2 U) to 26 weeks (54.3 U) and mean time of intake before meals changed from 17 minutes for BHI to ∼3 minutes with BIAsp. Incidence of hypoglycemia did not change during the study (baseline: 30.7%, week 26: 29.2%). HbA(1c) improved significantly from baseline (7.9 %) to weeks 12 and 26 (7.6% and 7.5%, respectively; p < 0.001). Mean PG profiles also showed significant improvements. As this is an observational study, some limitations should be considered such as the absence of a control group and a possible bias of increased medical attention.. Patients with long-standing type 2 diabetes can switch safely from BHI to BIAsp therapy, even if they receive intensified treatment, and they have no problems changing the timing of their insulin injections.

Topics: Aged; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Substitution; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Observation; Professional Practice

Glycaemic control is critical to prevent diabetic complications and mortality. This 6-month, open-label, observational study assessed the efficacy and safety of switching Japanese patients with type 2 diabetes from neutral protamine Hagedorn (NPH) insulin to insulin detemir.. Patients with type 2 diabetes (n = 126) receiving basal-bolus insulin therapy with NPH insulin plus rapid-acting insulin analogues were recruited. NPH insulin was replaced with insulin detemir for 6 months. Glycosylated haemoglobin (HbA(1c)), fasting plasma glucose (FPG), daily glucose levels and hypoglycaemia were monitored. Nocturnal quality of life was assessed by insulin therapy related quality of life at night questionnaire.. HbA(1c), FPG and body weight were all significantly reduced after treatment with insulin detemir for 6 months, without increasing severe hypoglycaemia. Insulin dose increased significantly over the same time. There were significant improvements in overall nocturnal quality of life, as well as well-being.. Treatment with insulin detemir for 6 months resulted in substantial benefits, including reduced HbA(1c), FPG and body weight, and improvements in nocturnal quality of life, without increasing hypoglycaemia.

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Japan; Male; Middle Aged; Quality of Life; Surveys and Questionnaires

To evaluate the effect of the long-acting basal insulin analog glargine compared with neutral protamine Hagedorn (NPH) insulin on the incidence of diabetic foot ulceration (DFU) in patients with diabetes in Germany.. A retrospective cohort study was performed using a representative German database (IMS Disease Analyzer) of patients with type 2 diabetes, who started a basal insulin therapy with either insulin glargine or NPH insulin, between July 2000 and September 2007, and continued this therapy for at least 24 months, and whose data were continuously documented.The occurrence of DFU was recorded beginning in the third year after therapy initiation and Kaplan-Meier curves were generated and compared using log-rank tests. Cox proportional hazard models were used to estimate the adjusted hazard ratio (HR) and 95% confidence intervals (CI) for the incidence of DFU.. Patients who fulfilled the inclusion criteria (n=23 395) had started either on insulin glargine (n=9638) or on NPH insulin (n= 13 757).After adjustment for demographic and clinical variables, it was demonstrated that the relative risk to diabetes patients of developing DFS is 64% lower with insulin glargine than with NPH insulin therapy (HR=0.6 I; p=0.0405).. The results suggest that, compared with NPH insulin, insulin glargine therapy significantly reduces the risk of DFS in patients with diabetes under real life conditions. Prospective long-term trials are needed to confirm these secondary data analysis results.. There were no external sources of funding for this study.The authors have no conflicts of interest to declare.

Topics: Aged; Cohort Studies; Diabetes Mellitus, Type 2; Diabetic Foot; Female; Germany; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Retrospective Studies; Risk Factors

To compare the risk of vascular disease, HbA1c and weight change, between first prescribed insulins in people with type 2 diabetes.. People included in THIN United Kingdom primary care record database who began insulin (2000-2007) after poor control on oral glucose-lowering agents (OGLD) were grouped by the number of OGLDs in their treatment regimen immediately before starting insulin (n = 3,485). Within OGLD group, Cox regression compared macrovascular (all-cause mortality, myocardial infarction, acute coronary syndrome and stroke) and microvascular disease (peripheral neuropathy, nephropathy, and retinopathy) between insulin type (basal, pre-mix or Neutral Protamine Hagedorn, NPH) while ANCOVAs compared haemoglobin A(1c) (HbA(1c)) and weight change.. Mean follow-up was 3.6 years. Rates of incident macrovascular events were similar when basal insulin was compared to pre-mix or NPH, adjusted hazard ratio versus basal: pre-mix 1.08 (95% CI 0.73, 1.59); NPH 1.00 (0.63, 1.58) after two OGLDs, and pre-mix 0.97 (0.46, 2.02); NPH 0.77 (0.32, 1.86) after three OGLDs. An increased risk of microvascular disease in NPH versus basal after 3 OGLDs, adjusted hazard ratio 1.87 (1.04, 3.36), was not seen after two agents or in comparisons of basal and pre-mix. At one year, after two OGLDs, weight increase was less with basal compared with pre-mix. After three OGLDs, mean HbA(1c) had reduced less in basal versus pre-mix or NPH at 6-8 and at 9-11 months, and versus pre-mix at 12-14 months.. We found no difference in the risk of macrovascular events between first insulins in the medium term when started during poor glycaemia control. The increased risk of microvascular events with NPH warrants further study. In certain groups, first use of basal insulin was associated with less gain in weight and decrease in HbA(1c) compared to other insulins.

Topics: Analysis of Variance; Body Weight; Cohort Studies; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Insulin, Isophane; Insulins; Proportional Hazards Models; Regression Analysis; Risk Assessment; United Kingdom; Vascular Diseases

Postprandial hyperglycemia is known to be associated with increasing cardiovascular mortality in type 2 diabetes mellitus patients. Cardio-ankle vascular index (CAVI) reflects arterial stiffness and is more useful for predicting coronary atherosclerosis than intima-media thickness. Premixed human insulin 30/70 (BHI30) containing rapid-acting insulin has been used conventionally as a biphasic insulin. Recently, a biphasic insulin analogue preparation, biphasic insulin aspart 30/70 (BIAsp30), containing ultrarapid-acting insulin has been approved and expected to improve postprandial hyperglycemia. The aim of this study was to clarify the effects of switching the biphasic insulin from BHI30 to BIAsp30 on arterial stiffness in type 2 diabetes mellitus patients. Twenty-six type 2 diabetes mellitus patients (glycosylated hemoglobin >6.5%) who were already receiving biphasic insulin therapy with BHI30 twice daily were observed for 3 months. Afterward, BHI30 was switched to BIAsp30. At 3 months after switching, relative mobility of the peak of LDL fraction decreased significantly (from 0.3462 ± 0.041 to 0.3356 ± 0.035, P < .01); and CAVI also decreased significantly (from 9.77 ± 1.11 to 9.35 ± 1.17 m/s, P < .005). A significant negative correlation was observed between the change in CAVI and change in 1,5-anhydroglucitol (1,5-AG) (r = -0.3929, P < .05). A stronger correlation between change in CAVI and change in 1,5-AG was observed in the subgroup of patients whose 1,5-AG levels were elevated after switching (r = -0.6261, P < .05) compared with all subjects. These results suggest that switching biphasic insulin from BHI30 to BIAsp30 improves arterial stiffness, and the improvement of arterial stiffness may be associated with improvement of postprandial hyperglycemia.

Topics: Aged; Arteries; Biphasic Insulins; Deoxyglucose; Diabetes Mellitus, Type 2; Female; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged

Despite the occurrence of a severe allergic reaction including an anaphylactic shock, a drug may remain essential and impossible to replace. This may be the case of insulin in a diabetic patient. We describe the case of an anaphylactic shock to human insulin in whom a desensitization protocol was successfully achieved.. A 50-year-old type 2 diabetic man presented one year after initiation of the insulin therapy an anaphylactic shock following the subcutaneous administration of a human insulin containing protamine (Insulatard®). A desensitization protocol to human insulin was performed and allowed to use two human insulin analogues containing no protamine (asparte and glargine), with a two-year event-free follow-up. Positive skin tests with insulin and protamine, and the presence of insulin specific IgE were evidenced of an IgE-mediated mechanism. Desensitization was monitored by skin tests, Maunsell's test, measurement of specific IgE and IgG4, and the basophil activation test. The decrease of basophil sensitivity to insulin is an early marker for tolerance induction.. The effectiveness of the desensitization to human insulin underlines the importance to define the modalities of such desensitization protocol and of the monitoring of the tolerance induction.

Topics: Anaphylaxis; Basophil Degranulation Test; Basophils; Biomarkers; Desensitization, Immunologic; Diabetes Mellitus, Type 2; Humans; Immunoglobulin E; Immunoglobulin G; Injections, Subcutaneous; Insulin, Isophane; Insulin, Long-Acting; Insulin, Regular, Human; Intradermal Tests; Isophane Insulin, Human; Male; Middle Aged; Predictive Value of Tests; Prognosis; Sensitivity and Specificity; Skin Tests; Treatment Outcome

To evaluate the safety and tolerability of once or twice daily neutral protamine hagedorn (NPH) insulin in fasting pregnant diabetics during Ramadan.. This was a prospective cohort study conducted during Ramadan 2006 and 2007. Twenty four pregnant diabetic women were given NPH insulin once at 5 pm or twice daily at 5 pm and 5 am. Demographic data, blood glucose control, insulin requirement, days of fasting and hypoglycemic episodes were analyzed.. Most women were parity 1 (37.5%) in their second trimester (54.2%) and worked during the daytime (87.5%). Fourteen women (58.3%) had gestational diabetes mellitus, nine women (37.5%) had type 2 and one (4.2%) had type 1 diabetes mellitus. There were significant reductions in mean fasting blood glucose (6.16 mmol/L versus 5.34 mmol/L, P = 0.001), glycosylated hemoglobin (HbA1c) (6.70% ± 0.91 versus 6.64% ± 0.96, P = 0.001) and serum fructosamine (232.4 mmol/L ± 24.0 versus 217.0 mmol/L ± 24.3, P = 0.001) after Ramadan compared to before Ramadan. Throughout the four weeks of Ramadan, home blood glucose monitoring showed a reducing trend and was within the acceptable limits. Insulin requirement was increased from the first to the fourth week with a reduction in insulin dose noted after (38.5 U/day) compared to before the start of Ramadan (40 U/day). Most women (79.2%) were able to fast for more than 15 days without any hypoglycemia or fetal demise.. Once or twice daily NPH insulin is a safe and tolerable option for pregnant diabetics who wish to fast during Ramadan.

Topics: Adult; Blood Glucose; Blood Glucose Self-Monitoring; Cohort Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Drug Administration Schedule; Fasting; Female; Humans; Insulin, Isophane; Islam; Parity; Pregnancy; Pregnancy in Diabetics; Prospective Studies; Treatment Outcome

We have made step-up titration protocol with biphasic insulin aspart-70/30 (BIAsp 30), and tried to achieve glycemic goals in poorly controlled Japanese type 2 diabetic patients. We summarized all results obtained to analyze the effectiveness of our protocol. The target of glycaemic control was defined as HbA1c over 7.0 %. In our insulin initiation protocol, all patients started a once-daily injection of BIAsp 30 before the breakfast in addition to their oral hypoglycaemic agents. The patients who could not achieve the target from 12 to 16 weeks after the start of insulin treatment proceeded to twice daily insulin injection before breakfast and dinner. Next, the patients who could not achieve the target from 12 to 16 weeks after the addition of another BIAsp injection proceeded to thrice daily insulin injection before each meal a day. The results of 39 patients were analyzed, and 10.3 % of all patients achieved the target after the start of once daily injection of BIAsp 30, 41.7 % achieved in twice daily injection of BIAsp, and 51.4 % achieved in thrice daily injection of BIAsp. Daily insulin dose at the end of each treatment was 9.3±4.1 U in once daily, 17.4±6.3 U in twice daily, and 28.4±10.4 U in thrice daily. Total body weight increase by 2.0±2.6 kg. The initiation and titration protocol with BIAsp 30 improved glycaemic control, and increased the number of patients with the achievement of glycaemic goals.

Topics: Aged; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Japan; Male; Middle Aged; Treatment Outcome

To evaluate treatment satisfaction before and after starting biphasic insulin aspart 30 (BIAsp 30) therapy in patients with type 2 diabetes mellitus (T2D) in the IMPROVE study Japan using the Diabetes Medication Satisfaction (DiabMedSat) questionnaire.. The DiabMedSat questionnaire assesses overall satisfaction with drug therapy for diabetes treatment in three domains: burden, efficacy and symptoms. Patients previously treated by oral anti-diabetic drugs in the IMPROVE study Japan answered the DiabMedSat questionnaires at baseline (week 0) and week 26 after starting BIAsp 30 treatment.. The mean scores for each domain at weeks 0 and 26, respectively, were: burden, 64.5 and 67.5 (p = 0.041); efficacy, 55.0 and 61.5 (p < 0.001); and symptoms, 70.9 and 68.1 (p = 0.049). The overall scores were 63.4 and 65.6, respectively (p = 0.079). With regard to burden, bothersome aspects were significantly improved with BIAsp 30 treatment at week 26, compared with treatment with oral anti-diabetic drugs at week 0. Major hypoglycemic episodes were very rare; most hypoglycemic events were minor and occurred during the daytime.. The study results indicate that BIAsp 30 does not adversely affect QOL in Japanese patients at insulin initiation.

Topics: Aged; Algorithms; Biphasic Insulins; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Hypoglycemia; Insulin; Insulin Aspart; Insulin, Isophane; Japan; Male; Middle Aged; Patient Satisfaction; Quality of Life; Surveys and Questionnaires; Time Factors

The objective of this study was to evaluate the short-term and long-term clinical and economic outcomes associated with insulin glargine or NPH insulin in patients with Type 2 diabetes mellitus (T2DM) inadequately controlled with oral anti-diabetic drugs in Switzerland, modeling the interaction between hypoglycemia and glycemic control (HbA1c).. A validated discrete event simulation model for T2DM was used to predict incidence of short-term complications (symptomatic, nocturnal and severe hypoglycemic events) and long-term complications (microvascular and macrovascular events), life expectancy, quality-adjusted life years (QALYs) and direct medical costs in patients treated with insulin glargine or NPH insulin. The model was populated with published Swiss patient characteristics with T2DM. Baseline risks of hypoglycemic events, utility decrements of diabetes-related long-term complications and the hypoglycemia fear score were derived from the literature. Relative risk reductions of hypoglycemia adjusted for HbA1c using insulin glargine compared with NPH insulin were based on a published negative binomial meta-regression analysis. Costs of severe hypoglycemia, micro- and macrovascular events were analyzed from literature whenever possible otherwise guideline-projected resource-use estimations were valued with Swiss official prices or tariffs in 2006 CHF. Simulations were run with 1,000 patients per cohort over a time horizon of 40 years. Incremental cost effectiveness ratios (ICERs) were presented as cost per QALY and per life year gained (LYG). Future costs and clinical benefits were discounted at 3.5%. Wide-range one-way sensitivity analyses were performed.. Insulin glargine was associated with an improvement in quality of life (0.098 QALYs per patient) and additional life expectancy (0.05 life years gained per patient) compared to NPH insulin. Incremental costs of CHF 2,578 resulted in an ICER of CHF 26,271 per QALY and CHF 51,100 per LYG. The cost per QALY was most sensitive to changes in costs, utility decrements and relative risk reductions of hypoglycemia.. This study evaluated, for the first time, the cost effectiveness of insulin glargine versus NPH insulin for the treatment of T2DM considering the interaction between glycemic control and hypoglycemia in Switzerland. The base case and sensitivity analyses demonstrated that insulin glargine proved to be cost-effective with respect to accepted willingness to pay thresholds and therefore represents good value for money.

Topics: Aged; Computer Simulation; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Models, Economic; Quality-Adjusted Life Years; Switzerland; Time Factors; Treatment Outcome

To assess the safety and efficacy of insulin analogues versus human insulin in pregnant women with pregestational diabetes.. We collected data on pregnant women with type 1 or type 2 diabetes who were attended at the Diabetes and Pregnancy Unit between January 1998 and April 2008 (N=351). Two hundred and forty one patients were treated with regular insulin and NPH and 110 were treated with different combinations of insulins including an insulin analogue (most of them with NPH and lispro).. There was no significant difference in terms of congenital malformation rate between groups (3.3% and 3.6%). The group on insulin analogue had slightly higher mean HbA1c during the first trimester than the group on human insulin (6.6 [1.0]% vs 6.9 [1.1]%; P=0,022) and needed smaller insulin doses during whole pregnancy. Severe hypoglycaemia was significantly less frequent among women treated with a rapid insulin analogue (2.3 vs 10.0%; P=0,025). Neonatal hypoglycaemia was significantly more frequent in the group treated with a rapid insulin analogue (34.9 vs 23.6%; P=0.043) due to the concomitant use of an insulin pump. Other obstetric and neonatal variables were not different between the two groups.. Our study shows that insulin analogues are safe during pregnancy in women with pregestational diabetes mellitus. Overall, glycaemic control, maternal and foetal outcome were similar to those with human insulin. The main advantage with respect to human insulin was to importantly reduce maternal severe hypoglycaemia.

Topics: Abnormalities, Drug-Induced; Adult; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Lispro; Insulin, Isophane; Insulin, Regular, Human; Logistic Models; Pregnancy; Pregnancy in Diabetics; Retrospective Studies

Premixed, or biphasic, insulins containing varying proportions of rapid- and intermediate-acting insulin components have been developed to limit the number of daily injections for patients who require both prandial and basal insulin injections.. This study was conducted to determine whether there were differences in glycosylated hemoglobin (HbA(1c)), weight change, hypoglycemia occurrence, and treatment discontinuation between patients treated with biphasic insulin aspart 30 (BIAsp-30) or biphasic human insulin 30 (BHI-30) in UK general practice.. Data were from >350 general practices from the United Kingdom. Patients were stratified by treatment regimen, diabetes type, and insulin status (naive or experienced). Changes in HbA(1c) and weight were compared from baseline (the date of the first prescription for either insulin) through 180 days of follow-up using ANCOVA. Hypoglycemia incidence rate ratios were compared, and the adjusted likelihood of hypoglycemia was evaluated by logistic regression. Rates of treatment discontinuation were compared using the Cox proportional hazards model.. The study included data from 7720 patients, of whom 1333 (17.3%) had type 1 diabetes and 4457 (57.7%) were male. Patients' mean (SD) age was 57.9 (19.8) years, and their mean body mass index was 29.5 (6.2) kg/m(2). The difference in HbA(1c) reduction was significant for BIAsp-30 compared with BHI-30 in insulin-naive patients with type 1 diabetes (0.57%; P = 0.045), insulin-naive patients with type 2 diabetes (-0.17%; P = 0.003), and insulin-experienced patients with type 2 diabetes (-0.23%; P = 0.007). The difference between insulins was not significant in insulin-experienced patients with type 1 diabetes. Five hundred ninety-four patients (7.7%) experienced at least one hypoglycemic event. The incidence rate ratio for reported hypoglycemia was significantly lower with BIAsp-30 compared with BHI-30 in insulin-naive patients with type 2 diabetes (0.74; 95% CI, 0.62-0.89; P = 0.001); the difference between insulins was not significant in the other groups. The adjusted hazard ratio for treatment discontinuation was significant for BIAsp-30 versus BHI-30 in insulin-experienced patients with type 2 diabetes (0.693; 95% CI, 0.543-0.884; P = 0.003), whereas the hazard ratios for the other groups did not reach statistical significance. There were no significant differences in weight change between BIAsp-30 and BHI-30 in any of the groups.. In this analysis, BIAsp-30 was associated with improved glycemic control (HbA(1c)) compared with BHI-30 in insulin-naive patients with type 1 or type 2 diabetes and insulin-experienced patients with type 2 diabetes. BIAsp-30 was associated with reduced hypoglycemia in insulin-naive patients with type 2 diabetes and lower rates of treatment discontinuation in insulin-experienced patients with type 2 diabetes. Cambridgeshire Research Ethics Committee: REC 08/H0305/47.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Biphasic Insulins; Body Weight; Child; Databases, Factual; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Retrospective Studies; Treatment Outcome; United Kingdom; Young Adult

Despite a wealth of clinical trial data supporting use of the premixed insulin analogue, biphasic insulin aspart 30 (BIAsp 30) in the treatment of type 2 diabetes mellitus (T2DM), there is limited documentation of its use in primary care-based clinical practice.. An observational study investigating the safety and efficacy of BIAsp 30 in routine clinical practice was conducted. Patients were followed up 3 and 6 months after initiating insulin treatment. Safety and efficacy measures were documented.. During the course of the study, 1154 patients were included (age range 20-95 years), of whom 89% completed the 6-month follow-up period. Mean HbA(1c) at baseline was 8.8% (73mmol/mol), and had improved to 7.2% (55mmol/mol) after 6 months of treatment. The rate of total hypoglycaemia at completion of the study was 4.1 events per patient year. Major hypoglycaemic events were rare (two in total).. BIAsp 30 was initiated safely and effectively in insulin-naïve patients with T2DM. The safety and efficacy profile observed in clinical trials was confirmed in this largely primary care-based setting in Sweden.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Biphasic Insulins; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Health Services Research; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Primary Health Care; Prospective Studies; Sweden; Time Factors; Treatment Outcome; Young Adult

Fast-acting insulin analogues (FAIAs) reduce hypoglycaemia and improve administration flexibility compared with short-acting human insulin (SHI). This analysis examines whether these benefits translate into cost offsets when comparing the total treatment costs for FAIA versus SHI used as basal-bolus therapy for treating type 2 diabetes (T2D).. Registry data covering the Danish population including demographic variables, prescription, hospital and primary care data formed the basis for analysis. To capture patients on basal-bolus therapy only, inclusion criteria were ≥2 prescriptions of either long-acting insulin analogues (LAIAs) or neutral protamine Hagedorn (NPH) insulin (basal component), and ≥2 prescriptions for either an FAIA or SHI (bolus component) during the inclusion period (1 January-31 December 2005). Patients using LAIAs (n = 521) or NPH (n = 2695) were analysed separately. Within each basal cohort, patients using FAIAs or SHI were matched regarding observable variables using propensity scores. Healthcare costs were analysed for a follow-up period (maximum 2 years post-inclusion).. Within each cohort, matching produced groups with similar observed covariates. Overall direct healthcare costs in the LAIA cohort were €4183 and €5289 for FAIA and SHI, respectively. In the NPH cohort, costs were €4940 and €4699 for FAIA and SHI, respectively. For both basal cohorts, cost differences between FAIA and SHI were not statistically significant.. As the propensity score model cannot account for unobserved variables, conclusions of causality cannot be made. Moreover, exclusion of indirect costs and application of hospital contact charges accrued in the discharge year only may result in an underestimation of overall healthcare costs.. Using matched cohorts, treating patients with T2D using basal-bolus regimens containing FAIAs was no more costly to the Danish healthcare system than regimens using SHI. FAIAs provide a flexible administration and optimal glucose control for a similar cost.

Topics: Adult; Costs and Cost Analysis; Denmark; Diabetes Mellitus, Type 2; Female; Hospital Charges; Humans; Insulin; Insulin, Isophane; Male; Middle Aged; Socioeconomic Factors

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin, Isophane; Insulin, Long-Acting; Patient Acceptance of Health Care; Weight Gain

This study was conducted to compare adherence and persistence of patients initiating basal insulin therapy with Levemir FlexPen versus those initiating basal insulin therapy with NPH via vial and syringe.. Data were gathered from a large US retrospective claims database, and included patients with type 2 diabetes that initiated basal insulin therapy with either Levemir FlexPen or NPH in vials. Patients were defined as adherent to therapy if they had a medication possession ratio (MPR) of ≥80% in the 12-month follow-up period and were defined as persistent with therapy if they had no gaps in insulin therapy in the follow-up period.. After controlling for confounders using logistic regression, patients initiating therapy with Levemir FlexPen had 39% higher adjusted odds of achieving an MPR ≥80% versus patients initiating therapy with NPH vial (OR 1.39; 95% CI: 1.04-1.85). Analysis of persistence using a Cox proportional hazards model indicated that patients initiating Levemir FlexPen had a 38% lower hazard of discontinuation compared to NPH vial (HR 0.62, 95% CI: 0.55-0.70).. Claims-based studies are limited to the extent that they accurately capture medical and pharmacy use. Also, relying on claims-based data limits the generalizability of the findings to similar populations and treatments.. These results suggest that persistence and adherence with insulin may be improved for patients initiating basal insulin therapy with Levemir FlexPen versus NPH vial.

Topics: Adult; Aged; Algorithms; Diabetes Mellitus, Type 2; Disposable Equipment; Female; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Medication Adherence; Middle Aged; Pharmaceutical Preparations; Retrospective Studies; Syringes

Tight glycemic control is central to reducing the risk of long-term macrovascular and microvascular complications of type 2 diabetes and the associated morbidity and mortality. However majority of the patients do not achieve glycemic targets (HbA1c < 7%). Once insulin treatment has been initiated, each patient's regimen must be optimized and intensified to reach the target. In many guidelines, initial insulin therapy comprises a single dose of long-acting insulin or premixed insulin. Basal insulin will help to control fasting plasma glucose (FPG) level, but postprandial glucose excursions make a significant contribution to the overall daily hyperglycemia of type 2 diabetic patients. BIAsp 30 is the most prescribed analog premix and consequently has the largest evidence base in terms of randomized controlled trials (RCTs) and observational data. It follows that BIAsp 30 is therefore the analog premix most likely to be used for insulin intensification, both from basal insulin and from BIAsp 30 regimens: OD to BID and from BID to TID.

Topics: Biphasic Insulins; Blood Glucose; Diabetes Complications; Diabetes Mellitus, Type 2; Drug Administration Schedule; Evidence-Based Medicine; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Patient Acceptance of Health Care; Postprandial Period; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Time Factors

Diabetes in pregnancy is associated with risks to the woman and to the developing fetus. Miscarriage, pre-eclampsia, preterm labour and congenital malformations in fetus are more common in women with pre-existing diabetes. Insulin requirement increases with each trimester of pregnancy in diabetic females. Treatment of gestational diabetes consists of medical nutrition therapy but insulin treatment forms the mainstay of the therapy. Monitoring glycemic control is essential in treatment of gestational diabetes. HbA1c level is helpful to differentiate between a pre-GDM and GDM. Majority of pregnant women with diabetes fail to achieve optimum glycemic control, mostly the postprandial plasma glucose with conventional insulin. In them, the best option is to administer ultra-short-acting analogs, insulin lispro or insulin aspart. These analogs improve the postprandial glucose control during pregnancy in both type 1 and type 2 diabetes and are considered safe and effective.

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Infant, Newborn; Insulin, Isophane; Pregnancy; Pregnancy in Diabetics; Pregnancy Outcome

To assess the role of adiposity on the pharmacodynamics of basal insulins NPH, detemir, and glargine in type 2 diabetes mellitus (T2DM), as estimated by glucose infusion rate (GIR) and endogenous glucose production (EGP) rate in the euglycemic clamp.. We examined the variables that best predicted GIR and EGP in 32-h clamp studies after treatment with subcutaneous injection of 0.4 units/kg NPH, detemir, and glargine in 18 T2DM subjects (crossover).. A multiple regression analysis revealed that BMI best predicted GIR variation during the clamp. BMI was inversely correlated with GIR in all three insulin treatments, but was statistically significant in detemir treatment only. BMI correlated positively with residual suppression of EGP in detemir, but not with glargine and NPH treatments.. Adiposity blunts the pharmacodynamics of all basal insulins in T2DM. However, as adiposity increases, the effect of detemir is lower versus NPH and glargine.

Topics: Adiposity; Aged; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Female; Glucose Clamp Technique; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged

To determine the relative contributions of basal hyperglycemia (BHG) versus postprandial hyperglycemia (PPHG) before and after treatment intensification in patients with glycated hemoglobin A(1c) (A1C) >7.0% while on prior oral therapy.. Self-measured, plasma-referenced glucose profiles and A1C values were evaluated from participants in six studies comparing systematically titrated insulin glargine with an alternative regimen (adding basal, premixed, or prandial insulin, or increasing oral agents). Hyperglycemic exposure (>100 mg/dL [5.6 mmol/L]) as a result of BHG versus PPHG was calculated.. On prior oral therapy, 1,699 participants (mean age 59 years, diabetes duration 9 years) had mean fasting plasma glucose (FPG) of 194 mg/dL (10.8 mmol/L), and mean A1C was 8.7%. BHG contributed an average of 76-80% to hyperglycemia over the observed range of baseline A1C levels. Adding basal insulin for 24 or 28 weeks lowered mean FPG to 117 mg/dL (6.5 mmol/L), A1C to 7.0%, and BHG contribution to 32-41%. Alternative regimens reduced FPG to 146 mg/dL (8.1 mmol/L), A1C to 7.1%, and the contribution of BHG to 64-71%. BHG contributions for patients with A1C averaging 7.6-7.7% were 76% at baseline and 34 and 68% after adding basal insulin or other therapies, respectively.. When A1C is >7.0% despite oral therapy, BHG routinely dominates exposure. Intensified therapy reduces A1C and changes this relationship, but BHG amenable to further intervention still accounts for one-third of total hyperglycemia after basal insulin treatment and two-thirds after alternative methods.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Insulin, Regular, Human; Isophane Insulin, Human; Male; Middle Aged; Randomized Controlled Trials as Topic; Treatment Outcome

To compare total costs and risk of hypoglycemia in patients with type 2 diabetes (T2D) initiated on NPH insulin versus glargine in a real-world setting.. This study used claims data (10/2001 to 06/2005) from a privately insured U.S. population of adult T2D patients who were initiated on NPH or glargine following a 6-month insulin-free period. A sample of 1698 glargine-treated and 400 NPH-treated patients met the inclusion criteria. Total and diabetes-related costs (inflation-adjusted to 2006) were calculated for 6-month pre- and post-index periods and compared between 400 patient pairs matched by a propensity score method.. In the post-index 6-month period, glargine patients incurred higher diabetes-related drug costs than NPH patients ($785 versus $632, p<0.0001) but there were no significant differences in diabetes-related medical or total costs, or all other total cost categories. Compared to the pre-index period, glargine patient costs declined by $2420 (p=0.058) whereas NPH patient costs declined by $4200 (p=0.046), with no statistically significant group differences (p=0.469). Among patients with hypoglycemia-related claims (0.75% in both groups), mean hypoglycemia-related costs were $85 and $202 for NPH and glargine patients, respectively (p=0.564).. Initiation of either NPH or glargine was associated with major cost reductions and infrequent hypoglycemia-related claims.

Topics: Adult; Diabetes Complications; Diabetes Mellitus, Type 2; Drug Therapy; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Patient Selection; Probability; Propensity Score; Retrospective Studies; United States

Topics: Diabetes Mellitus, Type 2; Eating; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin, Isophane; Middle Aged; Taraxacum

To compare hypoglycaemic events, glycated haemoglobin (HbA1c) and changes in body weight in Muslim patients with Type 2 diabetes receiving Humalog Mix 50 and human Mixtard 30 twice daily during Ramadan fasting.. Data were collected from Muslim patients with Type 2 diabetes attending primary care practices in North-West London, who were on Mixtard 30 insulin twice daily before Ramadan. Group 1 had their evening insulin changed to Humalog Mix 50 (n = 26) 2 weeks before Ramadan, i.e. taking Mixtard 30 at predawn meal and Humalog Mix 50 at the sunset meal during Ramadan. As the major proportion of the daily caloric intake was consumed at the sunset meal, the rationale of switching the evening dose from human Mixtard 30 to Humalog Mix 50 was to provide more rapid-acting insulin that has shorter time of onset and peak time for the large evening meal to improve the postprandial glucose control without increasing the risk of hypoglycaemia. Group 2 continued on Mixtard 30 twice daily (n = 26). All patients received structured education about how to identify and manage hypoglycaemia during Ramadan.. Group 1 had a mean HbA1c reduction of 0.48% (p = 0.0001) before and after Ramadan, whereas group 2 had a mean HbA1c increase of 0.28% (p = 0.007). Group 1 was associated with a small reduction of 0.04 (p = 0.81) in the mean number of hypoglycaemic events during Ramadan compared with before Ramadan, whereas group 2 was associated with an increase of 0.15 (p = 0.43), although these differences between the groups were not statistically significant following adjustment for baseline factors [LSM difference between groups = 0.135, p = 0.36, 95% confidence limits (-0.16, 0.43)].. Changing to humalog Mix 50 during Ramadan resulted in improvement in glycaemic control without increasing the incidence of hypoglycaemia.

Topics: Aged; Biphasic Insulins; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Insulin, Long-Acting; Islam; Male; Middle Aged; Risk Factors; Young Adult

To evaluate the cost-effectiveness of switching to biphasic insulin aspart (BIAsp 30) from human premix insulin for type 2 diabetes patients in the United States (US) setting.. The previously published and validated IMS Core Diabetes Model was used to project life expectancy, quality-adjusted life expectancy (QALE) and costs over 30 years. Patient characteristics and treatment effects were based on Canadian patients included the IMPROVE observational study (n = 311). Mean glycohaemoglobin (HbA(1c)) was 8.4%, duration of diabetes 16 years and prevalence of complications high at baseline. Simulations were conducted from the perspective of a third-party payer, with costs accounted in 2008 US dollars ($).. BIAsp 30 was projected to improve life expectancy by 0.202 years and QALE by 0.301 quality-adjusted life-years (QALYs), due to a reduced incidence of most diabetes-related complications. BIAsp 30 was associated with increased lifetime direct medical costs ($76,517 vs. 67,518) and an incremental cost-effectiveness ratio of $29,870 per QALY gained. Long-term outcomes were sensitive to the impact of BIAsp 30 on hypoglycaemia and changes in HbA(1c).. BIAsp 30 may represent a cost-effective treatment option in the US setting for advanced type 2 diabetes patients experiencing poor glycaemic control or hypoglycaemia on human premix insulin.. The application of treatment effect data derived from a Canadian cohort to the US setting was a limitation of the cost-effectiveness analysis. The findings of this cost-effectiveness analysis are not applicable to insulin-naïve diabetes patients.

Topics: Biphasic Insulins; Body Mass Index; Canada; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Monte Carlo Method; Patient Satisfaction; Quality of Life; Quality-Adjusted Life Years; Risk Factors; United States

To compare direct healthcare costs incurred by patients with type 2 diabetes in Denmark prescribed long-acting insulin analogues (LAIA) or intermediate-acting human insulin (NPH) in a basal-only regimen.. Demographic and socio-economic patient characteristics, hospital utilisation data, primary care visits, specialist physician visits and prescription data were extracted from registers covering the Danish population. Patients receiving basal insulin were identified during a 1-year inclusion period (2005) and allocated to a LAIA (n=303) or NPH group (n=8523). LAIA patients were then matched with NPH patients using propensity scores based on observable covariates. Annual direct healthcare costs were determined during a <2-year analysis period (2005-2006).. Direct healthcare costs, including prescription costs, were equivalent between groups. However, while most cost items were similar between groups, ambulatory visit costs were significantly lower in LAIA-treated patients (p=0.03), whereas insulin pharmacy costs were significantly lower in NPH-treated patients (p<0.001).. There was no difference in direct healthcare costs between patients using LAIAs or NPH insulin.

Topics: Adolescent; Adult; Ambulatory Care; Chi-Square Distribution; Child; Child, Preschool; Cost-Benefit Analysis; Denmark; Diabetes Mellitus, Type 2; Drug Costs; Female; General Practice; Health Care Costs; Humans; Hypoglycemic Agents; Infant; Infant, Newborn; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Logistic Models; Male; Metformin; Middle Aged; Models, Economic; Odds Ratio; Outcome and Process Assessment, Health Care; Pharmaceutical Services; Primary Health Care; Propensity Score; Referral and Consultation; Registries; Time Factors; Treatment Outcome; Young Adult

The clinical importance of glycaemic control in patients with diabetes has been well established. This study aimed to explore twice-daily biphasic insulin aspart 30 (BIAsp 30) for insulin initiation in patients with type 2 diabetes mellitus (T2DM) who had poor glycaemic control with human insulins (HIs). We use data from a Chinese cohort of the PRESENT study.. In the 3-month study, Chinese subjects with T2DM started insulin therapy with BIAsp 30 in routine care. Glycaemic control was measured by glycosylated hemoglobin (HbA(1C)), fasting plasma glucose (FPG) and posting plasma glucose (PPG). The safety assessment included hypoglycaemia and other adverse events.. A total of 1989 subjects previously treated with His were switched to BIAsp 30 for 3-month treatment. Mean HbA(1C), FPG and PPG were significantly improved after the therapy. The overall rate of hypoglycaemia decreased at the end of the trial except for the patients previously treated with long-acting insulin. Most of the events were minor and diurnal hypoglycaemia. Only one serious adverse drug reaction (SADR), a local hypersensitivity, was reported. The majority of the patients (> or = 96.7%) and physicians (> or = 84.7%) were either satisfied or very satisfied with the treatment using BIAsp 30 compared with previous HI therapy.. The BIAsp 30 treatment improved both glycaemic control and patients' satisfaction without increasing hypoglycaemia in T2DM subjects inadequately controlled by His.

Topics: Adult; Biphasic Insulins; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Prospective Studies; Treatment Outcome

Understanding treatment satisfaction (TS) for diabetes is increasingly important as treatment options increase. This study examines treatment satisfaction with NovoMix® 30 in an observational study in patients with type 2 diabetes.. The DiabMedSat assesses Overall, Treatment Burden, Symptom and Efficacy Treatment Satisfaction. The impact of type of pretreatment variables on TS was examined by ANOVA at baseline and week 26. Satisfaction at week 26 was examined by t-test and effect size. Linear regression models examined impact of prior treatment factors (age, gender, duration of diabetes, type of prior treatment and diabetes-related comorbidities) and current treatment factors (weight gain, hypoglycemic events, reaching therapeutic goal) on TS.. The data set comprised 17,488 persons. Prior treatment with insulin had a more positive impact on baseline satisfaction. At week 26, there were no differences between type of prior treatment groups in Overall, Symptoms and Burden TS. Current treatment with NovoMix 30 significantly improved TS. Regression analyses examining the combined effect of pretreatment factors and current treatment factors found that all factors except for age-impacted TS although the domains impacted varied.. Patients treated with NovoMix 30 reported improved treatment satisfaction, and the improvement is considered clinically meaningful to patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biphasic Insulins; Child; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Patient Satisfaction; Surveys and Questionnaires; Young Adult

This study reports on the effectiveness of exenatide compared to insulin glargine or NPH insulin in patients with type 2 diabetes mellitus, unable to achieve glycemic control with oral glucose-lowering therapies in a clinical care setting.. Patients with type 2 diabetes mellitus (n = 47) whose glycemia was not controlled adequately with oral hypoglycemic agents at maximum recommended therapeutic doses were initiated on exenatide therapy. Age-, sex-, and body mass index-matched patients receiving insulin glargine (n = 54) or NPH insulin (n = 23) served as controls. Data analysis included glycated hemoglobin, fasting and postprandial plasma glucose, lipid profile, body weight, and the occurrence of hypoglycemia.. A statistically significant reduction in glycated hemoglobin value was noted after initiating exenatide (pre-exenatide 9.7 +/- 1.4% vs. post-exenatide 8.7 +/- 1.5%; P < 0.05), which was comparable to values after insulin glargine (9.8 +/- 1.1% vs. 9.0 +/- 1.5%, respectively; P < 0.05) and NPH insulin (9.6 +/- 1.4% vs. 8.9 +/- 1.3%, respectively; P < 0.05). Exenatide therapy was associated with net weight loss (mean, 1.6 kg), but therapy with insulin glargine and NPH insulin was associated with weight gain (1.8 and 2.3 kg, respectively).. In a group of select Asian Indian type 2 diabetes patients with secondary failure to oral hypoglycemic agents seen at a diabetes center, exenatide treatment in combination with oral drug regimens resulted in significant lowering of glycated hemoglobin similar to insulin glargine or NPH insulin but with the additional benefit of weight loss, albeit a small amount.

Topics: Adult; Aged; Asian People; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Exenatide; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; India; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Peptides; Surveys and Questionnaires; Treatment Outcome; Venoms

Premixed insulin is effective to improve glycemic control; however, clinicians may be less likely to know which premixed insulin is appropriate for which patients. This study aimed to evaluate the effects of twice-daily injections of premixed insulin lispro on glycemic control in type 2 diabetic patients.. Forty type 2 diabetic patients, who had been treated with twice-daily injections of human protamine mixture 30/70 insulin for at least 12 months, were divided into two groups; one group whose blood glucose 2 hours after breakfast was greater than 200 mg/dL, was switched to lispro mix50, and the other group whose blood glucose 2 hours after breakfast < 200 was switched to lispro mix25.. Glycated haemoglobin (HbA1c) significantly improved in the Mix50 group from 8.3% to 7.5% (at 12 weeks; p < 0.05), and to 7.5% (at 24 weeks; p < 0.05). On the other hand, HbA1c levels in the Mix25 group were slightly decreased from 8.1% to 7.7% at 12 weeks (p < 0.05), and to 7.9% at 24 weeks (not significant). Both postprandial plasma glucose and fasting plasma glucose levels were significantly improved in the Mix50 group, but not in the Mix25 group. Overall, 95% of subjects preferred premixed lispro insulin from human insulin in the viewpoint of the timing of insulin injection by questionnaire analysis.. Switching from human protamine mixture 30/70 insulin to lispro mix50 twice-daily injection therapy in patients with high postprandial plasma glucose could improve their glycemic control and quality of life.

Topics: Aged; Biphasic Insulins; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Lispro; Insulin, Isophane; Male; Middle Aged; Postprandial Period; Protamines; Treatment Outcome

Weight gain is a significant problem in diabetic patients in terms of worsening glycemic control, increasing diabetic and cardiovascular morbidity and mortality, and contributing to social and psychological problems. In the present study, we evaluated the effects of a biphasic analog and regular NPH insulin mixtures on weight gain in patients with Type 2 diabetes mellitus (T2DM) over 1 year.. Group I consisted of 71 patients (29 men and 42 women) being treated with analog mixtures (insulin lispro 75/25 mix and biphasic insulin aspart 70/30 mix) twice daily; Group II consisted of 69 patients (23 men and 46 women) being treated with a regular insulin mixture (70/30) twice daily. Starting weight, body mass index, HbA1c, and hypoglycemic episodes were evaluated after 6 and 12 months.. Weight gain in Group I at 6 and 12 months was 1.41 ± 2.70 and 2.08 ± 3.74 kg, respectively. In Group II, weight gain at 6 and 12 months was 1.5 ± 3.0 and 2.29 ± 3.85 kg, respectively. Intragroup comparisons indicated that, for both groups, weight gain at 6 and 12 months differed significantly from the starting weight. However, no significant differences in weight gain were found between the two groups (P > 0.05).. The weight-increasing effects of an analog mixture of insulin and the NPH regular mixture of insulin appear to be similar. This should be taken into account when determining the type of insulin to use in treating T2DM patients.

Topics: Aged; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Lispro; Insulin, Isophane; Male; Middle Aged; Retrospective Studies; Weight Gain

This retrospective study used data from a primary care database to compare two insulin products in routine clinical practice for the treatment of type 2 diabetes in the UK.. Records were analyzed for patients with type 2 diabetes who had been initiated on biphasic insulin aspart 30 (BIAsp30) (n=632) or biphasic isophane human insulin 30 (BHI30) (n=762) and who had a glycated hemoglobin (HbA₁(c)) measurement at baseline (up to 6 months before the index date) and end of study (6-12 months after index date). Regression analyses were used to test for a statistically significant interaction between reduction in HbA₁(c) from baseline to end of study and the log-transformed average daily dose (logADD) of insulin.. With BIAsp30 a significantly lower dose of insulin (47.74 insulin units [IU]/day vs. 66.63 IU/day, P<0.0001) was required to obtain a similar HbA₁(c) reduction (1.71%-point vs. 1.55%-point, P=0.24). To achieve an additional reduction of 0.1 percentage points in HbA₁(c) (eg, reduction from 9% to 7.9% HbA₁(c) instead of from 9% to 8%), the dose of BIAsp30 would need to be increased by a factor of 1.15. For BHI30, a greater increase in dose would be needed to achieve the same additional HbA₁(c) reduction (dose increase by a factor of 1.74).. Clinically meaningful reductions in HbA₁(c) can be achieved at lower insulin doses with BIAsp30 treatment than with BHI30. Lower insulin doses may have important implications for medication costs.

Topics: Biphasic Insulins; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Linear Models; Male; Middle Aged; Multivariate Analysis; Retrospective Studies; United Kingdom

Results from a representative German database and from two German health services research studies revealed an unequal distribution between basal supported oral therapy (BOT) and basal-bolus therapy (ICT) regimens in Type 2 diabetics treated with either insulin glargine (GLA) or human insulin (Neutral Protamine Hagedorn; NPH). This study assesses whether this unequal distribution could be caused by a different persistence on the initial BOT regimen.. A Markov model was developed simulating the transition from BOT to ICT during a treatment course of 10 years. Data on persistence with BOT were obtained from the IMS® Disease Analyzer database. The model cohort consisted of German statutorily insured Type 2 diabetics starting a BOT either with insulin glargine or NPH insulin at a ratio of 1 : 1.. The number of Type 2 diabetics who switched from BOT to ICT differed between the two groups: After 2 years, 53% of glargine-treated patients and 31% of NPH-treated patients continued the BOT. After 6.5 years, all NPH-treated patients had switched to ICT. However, complete transition to ICT of glargine-treated patients occurred 1.75 years later. In the first quarter of Year 3, the model simulation resulted in BOT : ICT ratios comparable to those found in the real-world settings for GLA- and NPH-treated patients.. The simulation indicates that the persistence on the initial basal supported oral therapy is associated with the resulting BOT : ICT ratio. Therefore, the unequal distribution between BOT and ICT of Type 2 diabetics treated with either insulin glargine or NPH insulin might be caused by different persistence on the initial BOT regimen.

Topics: Administration, Oral; Aged; Databases, Factual; Diabetes Mellitus, Type 2; Female; Germany; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Markov Chains; Middle Aged; Time Factors

The OnceMix and INITIATE studies have indicated that biphasic insulin aspart 30 (BIAsp 30) is more effective than insulin glargine (IGlarg), in terms of glycohemoglobin reductions, in patients with type 2 diabetes initiating insulin therapy. The cost-effectiveness of BIAsp 30 versus IGlarg in the Chinese setting is estimated here.. The validated and peer-reviewed CORE Diabetes Model was used. The nephropathy, retinopathy, and stroke submodels were modified to incorporate available Chinese clinical data. Diabetes complication costs were derived from hospital surveys in Beijing and Chengdu. Simulated cohorts and insulin treatment effects were based on the OnceMix study for once-daily BIAsp 30 versus IGlarg and on the INITIATE study for twice-daily BIAsp 30 versus IGlarg. Life expectancy and direct medical costs were calculated. Projections were made over 30-year time horizons, with costs and life years discounted at 3% annually. Extensive sensitivity analyses were performed, including adjustments to cardiovascular risk for Chinese ethnicity.. Once-daily BIAsp 30 increased life expectancy by 0.04 years (12.37 vs. 12.33 years) and reduced direct medical costs by Chinese Yuan (CNY) 59,710 per patient (CNY 229,911 vs. CNY 289,621 per patient) compared with IGlarg in the OnceMix-based analysis. Twice-daily BIAsp 30 increased life expectancy by 0.08 years (12.99 vs. 12.91 years) and reduced direct medical costs by CNY 107,349 per patient (CNY 303,142 vs. CNY 410,491 per patient) compared with IGlarg in the INITIATE-based analysis. Improvements in life expectancy were driven by reduced incidences of most diabetes-related complications. Cost savings were attributable to lower lifetime insulin costs for BIAsp 30 compared with IGlarg in China. Lowered cardiovascular risk for Chinese ethnicity reduced the projected clinical improvements for BIAsp 30 but increased treatment-related lifetime cost savings.. BIAsp 30, either once- or twice-daily, improved projected life expectancy and reduced projected costs compared with IGlarg in the Chinese setting.

Topics: Asian People; Biphasic Insulins; Cardiovascular Diseases; China; Computer Simulation; Cost-Benefit Analysis; Diabetes Complications; Diabetes Mellitus, Type 2; Drug Costs; Female; Health Care Costs; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Models, Econometric; Quality-Adjusted Life Years; Risk

The IMPROVE study evaluated the safety and effectiveness of biphasic insulin aspart 30/70 (BIAsp 30) in type 2 diabetes patients in the routine practice. Here we present the results for patients from Italy.. Adverse events, hypoglycaemia, glycaemic control, patient treatment satisfaction and physician resource utilisation were assessed at baseline and 26 weeks.. Out of the 1371 patients enrolled, 84.1% (n=1153) were receiving BIAsp 30 at baseline (in accordance with local regulations), and were included in the study. Mean HlbA, reduction was--0.63% after 26 weeks (p < 0.001); 26.5% and 13.5% of patients reached the HbA(1c) targets of < 7% and < 6.5%, respectively. Fasting and postprandial blood glucose significantly decreased; 65% of patients were using BIAsp 30 once daily and 32% twice daily at final visit. Rates of major and minor hypoglycaemic events also significantly decreased. Small weight increase was observed, and total insulin daily dose increased from 0.29 IU/kg pre-study to 0.32 IU/kg at final visit.. In Italy, BIAsp 30 in the routine care improved glycaemic control and reduced hypoglycaemia; however, there was little intensification and titration. This may partly explain the relatively small improvement in glycaemic control in Italy compared with other countries in the IMPROVE study.

Topics: Aged; Biphasic Insulins; Cohort Studies; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; International Cooperation; Italy; Male; Middle Aged; Patient Satisfaction

The insulin analog glargine has a higher binding affinity than regular insulin for the insulin-like growth factor 1 receptor in vitro, raising questions about increased mitogenicity in vivo. Observational studies in humans have recently reported a potential differential association between insulin glargine and malignancies, but available evidence remains inconclusive. We directly compared glargine vs. neutral protamine Hagedorn (NPH) insulin's effects on cell proliferation in colonic mucosa and on formation of aberrant crypt foci in diabetic mice, i.e., early stages of colorectal cancer development. Mice (BKS.Cg-+Lepr(db)/+Lepr(db)/OlaHsd) were treated with insulin glargine (G), NPH insulin (NPH), or saline (NaCl). We assessed epithelial proliferation after long-term insulin treatment (18 weeks) by 5-bromo-2'-deoxyuridine and Ki67 staining and analyzed the formation of aberrant crypt foci (ACF) in mice treated with insulin glargine or NPH insulin or 10 weeks after initiation with 1,2-dimethylhydrazine. Insulin glargine treatment did not result in significantly different epithelial colonic proliferation compared to NPH insulin (G, 137 ± 22; NPH, 136 ± 15; NaCl, 100 ± 20 (relative proliferation index)), but both insulin-treated groups of mice had a higher proliferation index compared to the NaCl control group (p<0.001). Similarly, we observed no difference in ACF formation between glargine- and NPH-insulin-treated mice (G, 132 ± 12; NPH, 138 ± 9; NaCl, 100 ± 7 (relative number of ACF)), but ACF formation was significantly higher in insulin-treated mice than in NaCl-treated control mice (p=0.001). Chronic insulin treatment results in higher colonic epithelial proliferation and ACF formation, but the use of insulin glargine vs. NPH insulin is not associated with increased risk.

Topics: Animals; Cell Proliferation; Colon; Diabetes Mellitus, Type 2; Epithelial Cells; Female; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Mice

This is a case report of a patient with allergy to the rapid acting insulins and rapid acting analogs. Before trying insulin desensitization the treatment was changed to a basal-bolus regimen with glargine and glulisine with no signs of insulin allergy during the months after the start of the treatment.

Topics: Aged; Diabetes Mellitus, Type 2; Drug Hypersensitivity; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male

Skeletal muscle mitochondrial content is reduced in type 2 diabetes mellitus (T2DM). Whether hyperglycemia inhibits mitochondrial biogenesis and/or function is unknown. This study examined the effect of different levels of glycemia on skeletal muscle mitochondrial function in patients with T2DM.. Eleven patients with T2DM [9 males, 2 females; age, 52.8 +/- 2.5 yr (mean +/- se); body mass index, 30.2 +/- 1.1 kg/m(2)] in poor glycemic control were treated with insulin aspart and NPH insulin for a median period of 46 d (range, 31-59). Mitochondrial respiration and citrate synthase activity (a marker of mitochondrial content) were measured before and after treatment. Eleven healthy subjects (age, 53.3 +/- 2.7 yr; body mass index, 30.6 +/- 1.1 kg/m(2)) were included as controls.. Hemoglobin A1c (9.1 +/- 0.5 to 7.5 +/- 0.3%; P < 0.001) and fasting plasma glucose (12.7 +/- 1.1 to 6.5 +/- 0.3 mmol/liter; P < 0.001) were reduced after treatment. Mitochondrial respiration per milligram muscle was lower in T2DM compared to controls [substrates for complex I, 24% lower (P < 0.05); substrates for complex I+II, 17% lower (P < 0.05)]. Mitochondrial respiration and citrate synthase activity did not differ before and after improvements in glycemic control, but mitochondrial respiration correlated with fasting plasma glucose before (r(2) = 0.53; P < 0.05) but not after treatment [r(2) = 0.0024; not significant (NS)]. Mitochondrial respiration normalized to mitochondrial content did not differ between control subjects and patients with T2DM.. Mitochondrial respiration and content was not improved after significant improvements in glycemic control. However, severe hyperglycemia inhibited respiration reversibly, but moderate hyperglycemia and mitochondrial function were not correlated.

Topics: Adult; Aged; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Female; Fructosamine; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Mitochondria, Muscle; Muscle, Skeletal; Oxygen Consumption

Insulin glargine (glargine) and insulin NPH (NPH) are two basal insulin treatments. This study investigated the effect on glycaemic control of switching from a NPH-based regimen to a glargine-based regimen in 701 patients with type 1 (n= 304) or type 2 (n= 397) diabetes, using unselected primary care data.. Data for this retrospective observational study were extracted from a UK primary care database (The Health Improvement Network). Patients were required to have at least 12 months of data before and after switching from NPH to glargine. The principal analysis was the change in HbA(1c) after 12 months treatment with glargine; secondary analyses included change in weight and total daily insulin dose. Inconsistent reporting of hypoglycemic episodes precludes reliable reporting of this outcome. Multivariate analyses were used to adjust for baseline characteristics and confounding variables.. After adjustment, both diabetic cohorts showed statistically significant reductions in mean HbA(1c) 12 months after the switch, by 0.38% (p < 0.001) in type 1 patients and 0.31% (p < 0.001) in type 2 patients. Improvement in HbA1c was positively correlated with baseline HbA(1c); patients with baseline HbA(1c) > or = 8% had reductions of 0.57% (p < 0.001) and 0.47% (p < 0.001), respectively. There was no significant change in weight or total daily insulin dose while on glargine. The majority of patients received a basal-bolus regimen prior to and after the switch (mean 79.3% before and 77.2% after switch in type 1 patients, and 80.4% and 76.8%, respectively in type 2 patients, p > 0.05).. In routine clinical practice, switching from NPH to glargine provides the opportunity for improving glycaemic control in diabetes patients inadequately controlled by NPH.

Topics: Adult; Body Weight; Cohort Studies; Databases, Factual; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Retrospective Studies; Young Adult

Insulin detemir is a basal insulin analog designed to produce a superior pharmacokinetic profile to basal formulations of human insulin. It has shown consistently improved tolerability in comparison to neutral protamine Hagedorn (NPH) insulin in adult cohorts, but there are relatively few publications involving pediatric cohorts.. The efficacy and safety of insulin detemir in children with type 1 diabetes was assessed using data from the Turkish cohort of PREDICTIVE (a large, multinational, observational) study. The children investigated were using basal-bolus therapy involving NPH insulin or insulin glargine at baseline but were switched to insulin detemir as part of routine clinical care by their physicians.. Twelve weeks of treatment with insulin detemir significantly reduced mean hemoglobin A1c (9.7-8.9%, p < 0.001) and mean fasting glucose [185-162 mg/dL (10.3-9 mmol/L), p < 0.01]. Fasting glucose variability was also lower after treatment with insulin detemir than previously (on either NPH or glargine, p < 0.05). The frequencies of total, major and nocturnal hypoglycemic events were significantly reduced with insulin detemir relative to baseline, with an estimated mean of 6.89 fewer events/patient/yr overall (p < 0.001) and 2.6 fewer nocturnal events/patient/yr (p < 0.01). Weight and insulin dose remained relatively unchanged.. Twelve weeks of treatment with insulin detemir improved glycemic control and reduced hypoglycemia in children with type 1 diabetes. This improved tolerability might allow further dose titration and therefore additional improvements in glucose control.

Topics: Adult; Blood Glucose; Child; Cohort Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Tolerance; Europe; Fasting; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Safety; Turkey

This 18-month study assessed the improvement in glycaemic control and proportion of patients reaching glycated haemoglobin (HbA(1c)) targets with biphasic insulin aspart 30/70 (BIAsp 30) in clinical practice.. Type-2 diabetes patients failing on oral antidiabetic drugs (n=90) or existing insulin regimens (n=59) started or switched to BIAsp 30. Thiazolidinediones were stopped, metformin was continued. BIAsp 30 was given once daily (n=41), twice daily (n=96), or three times daily (n=12). Patients were taught self-monitoring and self-titration using an algorithm, adding daily doses of BIAsp 30 when necessary.. Mean baseline HbA(1c) was 8.4%, weight 85.4 kg, and age 57.9 years. All patients experienced significant reductions in HbA(1c) (mean 1.9%+/-0.1), fasting plasma glucose (mean 2.8 mmol/l), and post-prandial glycaemia (mean 2.9 mmol/l); 91% of patients achieved HbA(1c)<7% and 52% achieved HbA(1c) < or=6.5%. No major or nocturnal hypoglycaemia were reported; 15% of patients reported minor hypoglycaemia. Insulin-naïve patients gained mean 2.7 kg; patients who switched from another insulin lost weight (mean -0.6kg).. The results from this study from routine care suggest that BIAsp 30 may allow a large proportion of type-2 diabetes patients (90%) to improve glycaemic control and reach target HbA(1c)<7%, using self-titration.

Topics: Adult; Aged; Algorithms; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Netherlands; Patient Education as Topic

The patient was a 56-year-old man with type 2 diabetes and insulin allergy. He was administered glargine, which did not produce any allergic reactions, except for a small non-pruritic wheal. Thereafter, other insulin preparation could be administered. We consider this the first case of successful insulin desensitization by glargine administration.

Topics: Desensitization, Immunologic; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Hypersensitivity; Glycated Hemoglobin; Humans; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged

We studied the weight-sparing effect and treatment satisfaction when switching from NPH to insulin detemir in type 2 diabetes. Mean HbA(1c) (P<0.05) and waist circumference (P<0.05) were reduced while treatment satisfaction improved (P<0.03). No weight gain was observed. Detemir improves glycemic control, treatment satisfaction, and may provide additional weight-sparing benefits.

Topics: Aged; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Patient Satisfaction; Waist Circumference

The aim of this study was to compare incidence rates of heart failure, stroke, and acute myocardial infarction (AMI) in Type 2 diabetic patients using different types of insulin.. Included were patients with a diagnosis of Type 2 diabetes and at least one insulin prescription from May 2001 to July 2007. Incidence rate ratios (RRs) of heart failure, stroke, and AMI were estimated using Poisson regression with adjustment for age, gender, history of hypertension, dyslipidemia history, days supply, and duration of diabetes.. Incidence rates of heart failure, stroke, and AMI in the insulin glargine group were 306.9 (95%CI: [278.9, 334.8]), 174.8 (95%CI: [153.7, 195.8]), and 105.2 (95%CI: [88.9, 121.5]) cases per 10,000 person-years, respectively. After adjustment for covariates, the incidence rates of CVD events in the insulin glargine were comparable to those in the other long/intermediate acting insulin group (reference), except for AMI, which tended to be lower in the insulin glargine group (RR = 0.81, 95%CI: [0.65, 1.02]). Using the same reference, the incidence rate of stroke was higher in patients taking rapid/short acting insulin, premixed insulin, or mixed use of insulin except insulin glargine (RR = 1.20, 95%CI: [1.04, 1.40]).. This study suggested that insulin glargine use might be associated with a lower risk of AMI, compared to the other long/intermediate acting insulin use, and that insulin regimen of rapid/short acting insulin, premixed insulin, or mixed use of insulin except insulin glargine was associated with a higher risk of stroke using the same reference.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Cohort Studies; Diabetes Mellitus, Type 2; Female; Heart Failure; Humans; Hypoglycemic Agents; Incidence; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Myocardial Infarction; Retrospective Studies; Stroke

This study was conducted to quantify the long-term cost-effectiveness of insulin detemir (Levemir) versus intermediate-acting neutral protamine Hagedorn (NPH) insulin for the treatment of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) in Canada, and to assess the sensitivity of results to dis-utilities for hypoglycemic events. dagger Levemir is a trade name of Novo Nordisk, Princeton, NJ, USA RESEARCH DESIGN AND METHODS: The web-based IMS-CORE diabetes model has a menu-driven interface programmed in hypertext markup language (HTML). It was used to project lifetime (60 years for T1DM and 35 years for T2DM) clinical and economic outcomes for patients on detemir vs. NPH. Cohort characteristics, utilities, and costs were derived from published literature. For T1DM, clinical trial data for HbA(1c) improvement (detemir -0.94% +/- 1.07; NPH -0.82% +/- 1.01) from baseline, and rates of hypoglycemic events (major events: 0.20 vs. 0.80 per patient-year for detemir vs. NPH, respectively) were modeled. For T2DM, observational study data for HbA(1c) improvement (detemir -0.18%) from baseline, and reductions in hypoglycemic events (major events: 0.0995 vs. 1.33 per patient-year for detemir vs. NPH, respectively) were modeled. Base-case hypoglycemia dis-utilities were -0.0118 for major and -0.0035 for minor events. Sensitivity analyses were conducted on discount rate and hypoglycemia dis-utility.. Outcomes included costs of treatment/management and costs (and incidence) of diabetes-related complications. Incremental cost-effectiveness ratios (ICERs) were calculated from differences in total costs and quality-adjusted life-years (QALYs).. Average total costs for T1DM were $CAN 83 622 +/- 4585 for detemir and $CAN 72 016 +/- 4593 for NPH. QALYs increased by 0.475 years with detemir, with an ICER of $CAN 24 389/QALY. Average direct costs for T2DM were $CAN 74 919 +/- 6391 (detemir) and $CAN 69 230 +/- 6840 (NPH). QALYs increased by 0.305 years. The ICER was $CAN 18 677. Although detemir was associated with slightly lower costs for most complications, results were driven by the differences in rates and costs for hypoglycemic events, and their assumed dis-utility. Study limitations include the use of single trials for clinical assumptions and the lack of analyses for patient risk sub-groups.. Findings provide evidence for the cost-effectiveness of detemir vs. NPH in treating T1 and T2DM in Canada, and support the key role of assumptions regarding the impact of hypoglycemic events. Additional work is needed to determine the extent to which results are robust for different sub-groups of patients and for variation in assumptions around HbA(1c) improvements and hypoglycemic event rates.

Topics: Adult; Canada; Cost-Benefit Analysis; Diabetes Complications; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Incidence; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Life Expectancy; Male; Middle Aged; Models, Econometric; Quality of Life; Single-Payer System

The effectiveness of BIAsp 30 step-up therapy in achieving glycemic control in Japanese patients with type 2 diabetes mellitus was investigated. Study subjects were 99 patients with type 2 diabetes mellitus aged over 20 years who were judged to require insulin therapy due to poor glucose control (HbA1c level of > or =7.5%). BIAsp 30 dosage was determined by the patient's attending physician; coadministration of hypotensive agents and antilipemic agents was permitted, but OAD coadministration was limited to patients already receiving such drugs at the start of the study. Patients who did not achieve HbA1c <6.5% after 16+/-5 weeks with QD (Phase 1) were stepped up to BID (Phase 2). If patients still had not achieved HbA1c <6.5% after 16+/-5 weeks with BID, they were stepped up to TID (Phase 3). 55 of the 99 enrolled subjects completed the study and the rates of achievement of HbA1c <6.5% and HbA1c <7.0% were 45.5% and 74.5%, respectively. Of all registered subjects, 5.1% (5/99) achieved HbA1c <6.5% in QD, 19.5% (16/82) in BID, and 20.6% (7/34) in TID. Statistically significant reductions in HbA1c levels were recorded at the conclusion of each phase, with no incidents requiring intervention, indicating that BIAsp 30 step-up therapy is a safe, simple therapy that can be useful in achieving better glycemic control for Japanese patients with type 2 diabetes mellitus.

Topics: Administration, Oral; Adult; Aged; Biphasic Insulins; Diabetes Mellitus, Type 2; Diet, Diabetic; Drug Administration Schedule; Exercise; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Japan; Male; Middle Aged; Safety; Young Adult

Economic aspects and patient-reported outcomes play an increasing role in the choice of therapeutic options. The aim of the LIVE-DE study (Long-acting insulin glargine versus NPH insulin cost evaluation in Germany[DE]) was to assess expenditures incurred in the care of diabetic patients, as well treatment satisfaction of patients with type 2 diabetes treated with insulin glargine (GLAR) or NPH insulin (NPH).. A retrospective, non-interventional, cross-sectional study was undertaken in Germany of 1,602 insulin-treated patients (982 on GLAR, 620 on NPH), enrolled from 199 randomly selected general practitioner or internal medicine specialist practices. Total cost of diabetes care (insulins, oral antidiabetic drugs, glucagon use, consumables for insulin administration and blood glucose self-monitoring devices) were calculated from total recorded expenditures, for a period of six months, from the perspective of statutory health insurance. Cost data were obtained from publicly available sources, based on the prices in the year 2007. Patient treatment satisfaction was assessed using previously validated questionnaires (SF-12, PAID, DTSQ, ITEQ).. Physicians prescribed GLAR more often than NPH combined with oral antidiabetic drugs (43 % vs 16%), whereas NPH was more often used in an intensified insulin regimen compared to GLAR (79 % vs 49%). The mean total costs per patient over six months were lower in GLAR than NPH treated patients (658258 vs 685242 Euros [EUR]; p<0.001). The higher drug costs for basal insulin in the GLAR group (19497 vs 11674 EUR) were counterbalanced by lower costs for bolus insulin (96133 vs 158133 EUR), test strips (287137 vs 321142 EUR) and needles (4031 vs 4640 EUR). Only in the NPH group was glucagon use documented (in four patients). Patients treated with GLAR reported significantly higher treatment satisfaction. After adjustment of empirical results (by analysis of covariance), mean total costs of diabetes were higher in GLAR patients (+73.1 EUR; p<0.001). But treatment satisfaction remained significantly higher with GLAR.. Based on the comparison of total diabetes treatment costs under real-life conditions between glargine and NPH insulin based treatment regimens, these results indicate that the choice of a given treatment should be determined by medical advantages and patients' preferences. Because of a lower injection rate and a higher patient treatment satisfaction, the use of glargine as first-line therapeutic approach is justified in order to achieve target glycemic control in insulin dependent type 2 diabetics.

Topics: Aged; Blood Glucose Self-Monitoring; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Drug Costs; Female; Germany; Glucagon; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Needles; Patient Satisfaction; Quality of Life; Retrospective Studies; Surveys and Questionnaires

OBJECTIVE Pharmacological profiles of biphasic insulin aspart 30/70 (BIAsp 30) once daily (OD), twice daily (b.i.d.), and three times daily (t.i.d.) were compared with other insulin regimens in two crossover glucose clamp studies of insulin-treated type 2 diabetic patients. RESEARCH DESIGNS AND METHODS Study 1 consisted of BIAsp 30 OD, b.i.d., and t.i.d. versus biphasic human insulin 30/70 (BHI 30), OD (n = 24). Study 2 examined BIAsp 30 t.i.d. versus basal-bolus therapy (insulin glargine OD plus insulin glulisine t.i.d.) (n = 24). Pharmacokinetics/pharmacodynamics (PK/PD) were investigated over 24 h. RESULTS Study 1: PK and PD were markedly different between BIAsp 30 OD and BHI 30 OD: the maximum insulin concentration and glucose infusion rate (GIR) were higher for BIAsp 30; time to maximum metabolism was 1.7 h sooner for BIAsp 30. Study 2: both regimens showed three distinct prandial-related GIR peaks. GIR 24-h area under the curve for BIAsp t.i.d. was higher than for basal-bolus therapy: 2,585.2 vs. 2,289.2 mg/kg. CONCLUSIONS BIAsp had pharmacological advantages over BHI. BIAsp t.i.d. had a similar PD profile to basal-bolus therapy.

Topics: Administration, Oral; Biphasic Insulins; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Drug Administration Schedule; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Random Allocation

The aim of this prospective trial was to compare the effect of different long-acting insulin preparations injected at bedtime on glucose concentrations in patients with type 2 diabetes omitting breakfast and lunch the next day.. Twenty patients (ten women) with type 2 diabetes who were on an intensified insulin therapy participated. Mean (+/-SD) age was 63 +/- 10 years, diabetes duration 18 +/- 9 years, BMI 32.5 +/- 5 kg/m(2), and HbA(1c) 7.3 +/- 0.7%. Patients received neutral protamine Hagedorn (NPH) insulin, insulin detemir or insulin glargine for at least 2 months; doses were adjusted to achieve morning blood glucose levels of <7 mmol/l. At the end of the respective treatment period, the long-acting insulin was injected at bedtime (at 22:45 hours) as usual but patients refrained from breakfast and lunch the next day; glucose was measured by a continuous glucose monitoring system (CGMS).. Comparable glucose target ranges were reached at midnight (5.8 to 6.1 mmol/l) and at 07:00 hours (6.7 to 6.9 mmol/l) with all three insulin preparations, using mean doses of 29 +/- 10 U (NPH insulin), 33 +/- 13 U (insulin detemir), and 32 +/- 12 U (insulin glargine). Glucose levels between midnight and 07:00 hours were not significantly different for the three insulin preparations. Symptomatic hypoglycaemia did not occur from 08:00 to 16:00 hours; glucose concentrations during this time were slightly lower with NPH insulin than with insulin detemir (p = 0.012) and insulin glargine (p = 0.049).. Following bedtime injection of NPH insulin or of the analogues insulin detemir or insulin glargine, fasting glucose <7 mmol/l was achieved in the morning, without subsequent hypoglycaemia when participants continued to fast during the day.

Topics: Age of Onset; Aged; Blood Glucose; C-Peptide; Creatinine; Diabetes Mellitus, Type 2; Drug Administration Schedule; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged

Long-term studies involving large number of type 2 diabetic patients supplied evidence that constant adequate metabolic control may prevent the late (micro- and macrovascular) diabetic complications. In the present non-interventional, retrospective study, authors performed an analysis of type 2 diabetic patients who had been previously treated with biphasic human insulin (BHI) and their therapy was changed to biphasic analog insulin aspart 30/70 (BIAsp = NovoMix 30). The switch of the insulin therapy was carried out in years 2007 and 2008 with the cooperation of 50 accredited diabetes centers. Data were obtained at the time of therapeutical change and six months later. The number of suitable patients was 2898 with an age of 66.20 +/- 10.10 year, and the duration of diabetes was >10 years in 43% of the patients. After the six-month therapy with NovoMix 30, the mean HbA 1c level decreased statistically significantly from the initial value of 9.10 +/- 1.44% to 7.62 +/- 1.00% ( p < 0.001). The lipid profile also improved although target values were not always attained. A reduction was also observed in both systolic and diastolic blood pressure. Mean body weight decreased from 84.2 +/- 14.9 kg to 82.6 +/- 13.9 kg ( p < 0.01). All these changes occurred in spite of a significantly reduced daily insulin dose (48.4 +/- 17.6 IU) as compared with the initial value (49.0 +/- 17.4 IU, p < 0.001). A marked decrement was also observed in the frequency of hypoglycemic reactions. These results confirm that treatment with NovoMix 30 insulin leads to a significant amelioration of glycemic control as reflected by the decreased level of HbA 1c and the higher proportion of patients attaining the target value, as well as the lower frequency of hypoglycemic episodes. The significant improvements in cardiovascular risk factors are also important, but the explanation is still missing and would require the accomplishment of prospective, controlled studies.

Topics: Adult; Aged; Biphasic Insulins; Blood Glucose; Blood Pressure; Body Weight; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Glycated Hemoglobin; Humans; Hungary; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Retrospective Studies; Risk Factors; Time Factors; Weight Gain

This article reevaluates the hypoglycemic episodes reported as severe in the Treat-to-Target Trial comparing insulin glargine and NPH insulin use in patients with inadequately controlled type 2 diabetes.. Case report forms from the Treat-to-Target Trial were reviewed to identify additional severe hypoglycemic events and to further characterize those events already identified. Severe hypoglycemia was defined as symptoms consistent with hypoglycemia requiring assistance of another person and associated with either glucose levels < or =56 mg/dL or prompt recovery after oral carbohydrate intake, intravenous glucose administration, or glucagon injection.. This analysis confirmed that severe hypoglycemia was similarly uncommon with both insulins (insulin glargine [n = 367], nine patients, 14 events; NPH insulin [n = 389], nine patients, 13 events); all hypoglycemic events for glargine and nine for NPH were treated effectively at home. All severe hypoglycemic episodes were associated with sulfonylurea use. A review of case report forms demonstrated inconsistencies in identification of severe hypoglycemia (seven of 14 severe events for glargine and three of 13 severe events for NPH were coded as moderate).. The rate of severe hypoglycemia in this trial was low. Difficulties in gathering and interpreting hypoglycemia data highlight the need for more objective methods.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Sulfonylurea Compounds

The aim of this subanalysis of the IMPROVE study was to evaluate the safety and effectiveness of initiating biphasic insulin aspart 30/70 (BIAsp 30) in type 2 diabetes patients uncontrolled on oral antidiabetic drugs (OADs).. IMPROVE is a 26-week, open-label, non-randomised, international observational study in type 2 diabetes patients prescribed BIAsp 30 in routine clinical practice. The total cohort comprised 52 419 patients from various pre-study therapies. Here results from the subgroup of previously insulin-naïve patients are reported. Changes in glycated haemoglobin (HbA(1c)), fasting blood glucose (FBG), postprandial blood glucose (PPBG), weight, dose, proportion of patients achieving HbA(1c) < 7.0%, and rates of major and minor hypoglycaemic events were recorded. Treatment satisfaction was assessed using a validated questionnaire.. A total of 29 160 insulin-naïve patients were included; mean age 55.6 years, diabetes duration 7.3 years, baseline HbA(1c) 9.24%. Significant reductions were seen for HbA(1c) (-2.12%; p < 0.0001), FBG (-4.07 mmol/L; p < 0.0001) and PPBG after all meals (mean: -5.27 mmol/L; p < 0.0001); 39.2% of patients achieved HbA(1c) < 7.0% without hypoglycaemia. Better glycaemic control was seen in patients treated with BIAsp 30 twice-daily (BID) both at baseline and final visit, or BID at baseline and three-times daily at final visit, compared with other regimens. The rate of major hypoglycaemic events decreased significantly, while the rate of minor hypoglycaemic events increased. Better glycaemic control and a lower rate of minor hypoglycaemia were observed in patients using BIAsp 30 without OADs than with OADs. There was no clinically relevant change in weight (-0.07 kg; p < 0.0001). At final visit, 59.7% of patients were extremely/very satisfied with treatment, compared with 10.2% at baseline.. This open-label, non-randomised, observational study demonstrated that initiating insulin therapy with BIAsp 30 significantly improved glycaemic control in insulin-naïve patients previously poorly controlled on OADs. The rate of major hypoglycaemia was reduced and treatment satisfaction increased after initiation of BIAsp 30. Furthermore, better glycaemic control was achieved with BIAsp 30 without OAD compared to with OAD.

Topics: Administration, Oral; Adult; Aged; Biphasic Insulins; Blood Glucose; Cohort Studies; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Patient Satisfaction; Retrospective Studies; Surveys and Questionnaires; Treatment Failure; Treatment Outcome

Recent publications of data extracted from population registries have suggested a possible relationship between treatment with insulin glargine and increased incidence of cancer/breast cancer. The aim of the present study was investigate this possible relationship using data from the manufacturer's (sanofi-aventis) pharmacovigilance database.. We analysed the manufacturer's (sanofi-aventis) pharmacovigilance database for all randomised clinical trials (RCTs; Phase 2-4) comparing insulin glargine with any comparator in type 1 or type 2 diabetes. We identified all serious adverse events coded under the System Organ Class of 'neoplasms, benign, malignant and unspecified'. Treatment-emergent neoplasms judged to be malignant were included in this analysis.. The database included 31 studies, 12 in type 1 diabetes and 19 in type 2 diabetes. Twenty compared insulin glargine with NPH insulin, 29 were parallel-group studies and two had a crossover design. Studies were generally of 6 months' duration, except for trial reference number 4016 (n = 1,017), which had a duration of 5 years. Overall, 10,880 people were included in the analysis (insulin glargine, 5,657; comparator, 5,223). Forty-five people (0.8%) vs 46 people (0.9%) reported 52 and 48 cases of malignant cancer in the insulin glargine and comparator groups, respectively (RR 0.90, 95% CI 0.60-1.36). Skin (12 people with 16 events vs six people with seven events, RR 1.85, 95% CI 0.69-4.92), colon and rectum (six vs ten people, RR 0.55, 95% CI 0.20-1.52), breast (four vs six people, RR 0.62, 95% CI 0.17-2.18) and gastrointestinal tract (six vs four people, RR 1.38, 95% CI 0.39-4.90) were the most commonly reported sites.. In these 31 RCTs, insulin glargine was not associated with an increased incidence of cancer, including breast cancer, compared with the comparator group.

Topics: Adolescent; Adult; Child; Databases, Factual; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Incidence; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Neoplasms; Random Allocation; Randomized Controlled Trials as Topic

Recent reports have described different risks of acute myocardial infarction (AMI) in association with specific oral antidiabetic medications. The present study compared the AMI incidence rates in new users of traditional neutral protamine Hagedorn (NPH) insulin and a long-acting synthetic insulin analog for basal insulin therapy. We retrospectively examined in-patient medical claims for AMI in a cohort of oral agent-treated patients with type 2 diabetes mellitus after the initiation of basal insulin therapy with either NPH (n = 5,461) or insulin glargine (n = 14,730) in a national administrative claims database comprising >30 managed healthcare plans in the United States. Poisson regression and Cox proportional hazards regression models, as well as the propensity score methods, were used to compare the subsequent AMI incidence rates after the initiation of NPH or glargine. At a mean follow-up of 2 years, the unadjusted AMI incidence was 17.6/1,000 person-years after the initiation of NPH versus 11.5/1,000 person-years after initiation of glargine (rate ratio 1.53, 95% confidence interval 1.29 to 1.81). The Cox regression model (hazard ratio 1.39, 95% confidence interval 1.14 to 1.69) and sensitivity analyses (hazard ratio range 1.30 to 1.56) showed a greater risk of AMI in the NPH group than in the glargine group. Propensity matched (1:1) analysis yielded similar results (odds ratio 1.55, 95% confidence interval 1.23 to 1.96 for NPH vs glargine). In conclusion, these results suggest that the initiation of basal insulin therapy with NPH rather than glargine in patients with type 2 diabetes mellitus is associated with a greater risk of AMI.

Topics: Age Distribution; Confidence Intervals; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Hypoglycemic Agents; Incidence; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Poisson Distribution; Probability; Prognosis; Proportional Hazards Models; Registries; Retrospective Studies; Risk Assessment; Severity of Illness Index; Sex Distribution; Statistics, Nonparametric; United States

Topics: Amino Acid Substitution; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Obesity

Basal insulin and premix insulin are commonly prescribed first-line insulin therapies for patients failing to maintain glycaemic control on oral therapy. When control on these insulins starts to drift, premix analogues, such as biphasic insulin aspart 30/70 (BIAsp 30), are a simple and effective tool for intensification as they can be injected up to three-times daily (TID). However, at present, international recommendations for intensification of insulin therapy using premix analogues are limited and specific guidance on dosing is not available for many scenarios.. In October 2008, an international expert panel met to review the current guidelines for insulin intensification with BIAsp 30 in patients with type 2 diabetes, with the aim of developing practical guidance for general and specialist practitioners.. Simple treatment algorithms have been developed for (i) patients on basal insulin (human or analogue) once daily or twice daily (BID) who need intensification to BIAsp 30 BID, and (ii) patients on BIAsp 30 once daily or BID who can be intensified to BIAsp 30 BID or TID. As well as these algorithms, specific guidance has been provided on dose transfer (from basal insulin to BIAsp 30), dose split (when intensifying from once daily to BID), and combination oral therapies. In addition, a guide to dose titration is included.. The guidelines presented here should enable general or specialist practitioners to use BIAsp 30 to intensify the insulin therapy of patients failing on basal insulin or BIAsp 30 once or twice daily.

Topics: Algorithms; Biphasic Insulins; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Treatment Failure

Treatment satisfaction (TS) is an important patient reported outcome (PRO) in diabetes as it is correlated with outcomes necessary for optimal treatment (e.g., compliance, self-management behaviour). The objective of this study was to examine the responsiveness of the DiabMedSat, a disease-specific PRO measure, assessing Overall, Burden, Efficacy and Symptom TS.. The DiabMedSat was included in an open label, observational study of the safety and efficacy of biphasic insulin aspart 30 (NovoMix 30) in routine practice with type 2 diabetes. Responsiveness analyses, examining both internal and external responsiveness, were conducted and minimally important differences (MID) assessed.. In 18,817 patients, all TS scores significantly improved after 26 weeks of treatment (p<0.001). The effect sizes for these changes were above 0.5 indicating that the ability to detect change was moderate-to-large in size. Significant differences were found for all TS scores comparing patients who met their HbA(1c) goal, who improved but did not meet goal and who did not improve (p<0.01), and for patients who experienced a minor hypoglycaemic event and those who did not (p<0.001). DiabMedSat scores were able to detect changes in patients' own global rating of satisfaction (MID ranging from 5.3 to 11.7) and in physician-rated satisfaction with patients' HbA(1c) improvement (MID ranging from 5.3 to 10.2).. In the context of an observational study, the DiabMedSat has been shown to be highly responsive to change and can be considered as an acceptable PRO measure for TS in diabetes.

Topics: Attitude of Health Personnel; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Longitudinal Studies; Male; Middle Aged; Multicenter Studies as Topic; Patient Satisfaction; Self Care; Treatment Outcome; Weight Loss

Topics: Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Prospective Studies; Saudi Arabia

To evaluate the long-term cost-effectiveness of transferring type 2 diabetes patients to an insulin detemir regimen after failure to achieve adequate control with oral antidiabetic agents (OADs) alone, or in combination with neutral protamine hagedorn (NPH) insulin, or with insulin glargine in Germany.. A computer simulation model of diabetes was used to make long-term projections of future clinical outcomes and direct medical costs based on findings from a German subanalysis of the PREDICTIVE trial. The study analysed the impact of converting patients failing their current treatments to an insulin detemir regimen. Therapy conversion to insulin detemir +/- OADs was associated with a significant reduction in glycosylated haemoglobin (HbA(1)c) compared with OADs alone, NPH insulin +/- OADs, and insulin glargine +/- OADs. Across all three groups, hypoglycaemia rates decreased by 80% and patients lost an average of 0.9 kg of body weight during treatment with insulin detemir +/- OADs.. Therapy conversion to insulin detemir +/- OADs was projected to improve life expectancy by 0.28 years compared with OADs alone, and by 0.13 years compared with the NPH and glargine regimens. Transfer to insulin detemir was associated with improvements in quality-adjusted life expectancy of 0.21 quality-adjusted life years (QALYs) over OADs alone, 0.28 QALYs over NPH +/- OADs, and 0.29 QALYs over glargine +/- OADs. Insulin detemir was associated with savings over patient lifetimes due to reduced diabetes-related complications in all three comparisons.. Therapy conversion to insulin detemir +/- OADs in type 2 diabetes patients failing OADs alone, NPH or insulin glargine regimens was associated with improvements in life expectancy, quality-adjusted life expectancy and cost savings in all three scenarios evaluated.

Topics: Administration, Oral; Body Weight; Costs and Cost Analysis; Diabetes Complications; Diabetes Mellitus, Type 2; Female; Germany; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Life Expectancy; Male; Middle Aged; Quality-Adjusted Life Years

The PRESENT study was a 6-month multinational observational study in patients with type 2 diabetes receiving biphasic insulin aspart 30 (BIAsp 30). Data from PRESENT were analysed according to predefined subgroups stratified by age, body mass index (BMI) and ethnic origin. Achieved HbA1c levels were similar in each of: four age subgroups (<40 years 7.82%, 40-50 years 7.70%, 50-60 years 7.75%, >or=65 years 7.75%); five BMI subgroups (<25 kg/m(2): 7.78%, 25-30 kg/m(2): 7.58%, 30-35 kg/m(2): 7.57%, 35-40 kg/m(2): 7.74%, >or=40 kg/m(2): 7.93%); and Asian/Pacific Islander, Middle Eastern/Asian, White ethnic-origin subgroups (7.78%, 7.40%, 7.59%, respectively). The Black ethnic-origin subgroup had a higher baseline HbA1c of 11.61% (other groups 9.29-9.63%) and achieved a final HbA1c of 8.59%. Major hypoglycaemia was reported by fewer than 1% of subjects in any subgroup at end of study; overall end of study hypoglycaemia rates were less than four events/subject year (all subgroups). In conclusion, data from subgroups in the PRESENT study indicate that BIAsp 30 can be initiated and titrated effectively to help patients of all ages, of all degrees of obesity, and from a variety of ethnic origins, to achieve clinically relevant improvements in glycaemic control with low rates of hypoglycaemia.

Topics: Adult; Aged; Biphasic Insulins; Blood Glucose; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Ethnicity; Female; Humans; Hypoglycemia; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Multicenter Studies as Topic

Hypoglycaemia is the most common adverse event associated with intensive conventional insulin therapy (ICT). This study compared the risk of exercise-related hypoglycaemia in type 2 diabetes patients receiving either basal insulin glargine or NPH insulin.. In a prospective trial, 122 ICT patients (glargine n=60, NPH n=62) had a standardized treadmill test, monitored by capillary lactate concentration. Blood glucose (BG) profiles were performed the day before, during and the day after the exercise test, with the patients on a strict carbohydrate-defined diet. All patients had been on a stable ICT scheme for at least three months and had an HbA1c below 7.5%.. BG at the beginning of the exercise test, BG decline and lowest BG during the test were comparable between the two groups. The episodes of mild hypoglycaemia (BG<3.3 mmol/l) and amounts of additional carbohydrate intake due to mild symptoms of hypoglycaemia (BG 3.3-5.0 mmol/l) were not significantly different. No episodes of hypoglycaemia occurred during several hours after the exercise.. Moderate physical activity can be recommended for well-controlled type 2 diabetes patients receiving ICT, independently of glargine or NPH as basal insulin and without risk of exercise-induced hypoglycaemia.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Exercise; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Middle Aged

Topics: Abdominal Wall; Adipose Tissue; Aged; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Injections, Subcutaneous; Insulin, Isophane; Lipodystrophy

Type 2 diabetes is an increasing problem in China, yet there is a paucity of data regarding the cost-effectiveness of pharmacological interventions in the Chinese setting.. Previous data were obtained from PRESENT (Physicians' Routine Evaluation of Safety and Efficacy of NovoMix 30 Therapy), a multi-country, single-arm, observational study where type 2 diabetes patients poorly controlled with biphasic human insulin (BHI) were converted to biphasic insulin aspart 30 (BIAsp30); the Chinese subgroup experienced an improvement in HbA(1c) and a reduction in hypoglycaemic events. A published and validated computer simulation model of diabetes (the CORE Diabetes Model) was used to estimate the long-term clinical and cost consequences of switching to BIAsp30 from BHI in the Chinese setting. Treatment effects and patient characteristics were derived from PRESENT and country-specific published sources. Primary research was performed to ascertain patient management practices and diabetes-related complication costs. Risks of modelled complications were derived from landmark clinical trials and epidemiological studies. Costs and clinical projections were made over patient lifetimes from a third-party payer perspective and discounted at 3% annually. Extensive sensitivity analyses were performed.. Conversion to BIAsp30 from BHI was projected to improve discounted life expectancy by 0.38 years per patient (9.91 vs 9.53 years) and quality-adjusted life expectancy by 0.91 quality-adjusted life years (QALYs) per patient (6.32 vs 5.41 QALYs). Conversion to BIAsp30 was associated with increased direct medical costs of Chinese Yuan (CNY) 1751 per patient, due to higher pharmacy and management costs (CNY +19,007), offset by reduced diabetes-related complication costs (CNY -17,254) over patient lifetimes. BIAsp30 was associated with an incremental cost-effectiveness ratio of CNY 1926 per QALY gained.. BIAsp30 was projected to substantially improve clinical outcomes but was associated with increased lifetime medical costs. BIAsp30 would be considered cost-effective in China given a willingness-to-pay threshold of CNY 100,000 per QALY gained in type 2 diabetes patients poorly controlled on BHI.

Topics: Biphasic Insulins; China; Cost-Benefit Analysis; Diabetes Complications; Diabetes Mellitus, Type 2; Health Care Costs; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Middle Aged; Quality-Adjusted Life Years

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Costs; Health Care Costs; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; United States; United States Food and Drug Administration; Weight Gain

Biphasic insulin aspart NovoMix 50 is a new premixed insulin preparation that contents 50% of ultra-short acting insulin analogue aspart and 50% of protaminated insulin aspart. As compared to NovoMix 30, NovoMix 50 results in a better control of postprandial hyperglycaemia thanks to a greater proportion of the ultra-short acting insulin analogue. Another preparation called NovoMix 70 extends the panel of NovoNordisk, and will be soon commercialised in Belgium. These premixed insulin preparations can be used in one (rather rarely), two (most classically) or three (more and more frequently, i.e. before each of the three main meals) subcutaneous injections per day. They are used in the management of type 2 diabetes, eventually in association with metformin. These insulin preparations are available in Penfill cartridges for NovoPen. The launch of premixed insulin preparations, containing different proportions of short-acting and intermediate insulin formulations, offers a greater flexibility to medical doctors and facilitates the selection, according to the moment of the day, of the insulin mixtures that allow the best control of prandial and basal glycaemia, while limiting the risk of hypoglycaemia.

Topics: Biphasic Insulins; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane

The PREDICTIVE study is a multinational observational study designed to follow up patients with diabetes who started insulin detemir (IDet) in routine care. Recruitment started in June 2004 and is ongoing in some countries.. We report 12-week follow-up data for patients with type 1 (T1D) or type 2 diabetes (T2D) in the European cohort who, as part of basal-bolus therapy, switched from once- (qd) or twice-daily (bid) neutral protamine Hagedorn insulin (NPH) to qd IDet. End-points - evaluated from patients' records and diaries - were incidence of serious adverse drug reactions, glycaemic parameters, hypoglycaemia and weight change.. A total of 3637 patients were included, n = 1500 T1D [mean age 40.9 years, body mass index (BMI) 25.0 kg/m(2), glycosylated haemoglobin (HbA(1c)) 7.9%] and n = 2137 T2D (mean age 60.5 years, BMI 31.9 kg/m(2), HbA(1c) 8.0%). IDet was well tolerated. Lower overall, major and nocturnal rates of hypoglycaemia were observed in T1D and T2D patients switching from NPH to IDet (overall, T1D: 38.2-18.56 episodes/patient year, p < 0.001; T2D: 13.8-3.3 [corrected] episodes/patient year, p < 0.001). Switching from bid NPH to qd IDet resulted in significant 12-week reductions in HbA(1c) (T1D: -0.40%; T2D: -0.56%; both p < 0.001). Switching from qd NPH to qd IDet, resulted in HbA(1c) reductions of: T1D -0.52%; T2D -0.56%; both p < 0.001. Fasting blood glucose levels were also significantly reduced in patients with T1D or T2D. Overall mean weight changes were: T1D: 0.0 kg, T2D: -0.2 kg after 12 weeks.. In routine care, patients with T1D or T2D may be switched from NPH to IDet qd as part of a basal-bolus regimen.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Prospective Studies

To evaluate the beta cell functions with and without human Isophane insulin treatments.. Thirty patients with type 2 diabetes mellitus who followed the human Isophane insulin therapeutic regimen at bedtime were given 100 g steamed bread tests in two consecutive days. Then the human Isophane insulin treatments were stopped and the 100 g steamed bread tests were repeated in the next day. The fasting and 1, 2, 3 h after meal plasma glucose, serum insulin, C-peptide and proinsulin were measured.. (1) The fasting and 1,2,3 h after meal plasma glucose increased while the serum insulin decreased after the human Isophane insulin treatments were stopped (P<0.05). (2) The fasting and 1, 2 h after meal C peptide increased (P<0.05) after the human Isophane insulin treatments were stopped. (3) The fasting and 1, 2, 3 h after meal proinsulin increased after the human isophane insulin treatments were stopped (P<0.05). (4) The area under the insulin curve decreased, while, the area under the C peptide increased after the human Isophane insulin treatments were stopped (P<0.05).. Human Isophane insulin treatments should not be stopped to evaluate the beta cell functions of the patients who are undergoing Isophane insulin treatment.

Topics: Adult; Aged; Area Under Curve; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Glucose Tolerance Test; Humans; Insulin; Insulin-Secreting Cells; Insulin, Isophane; Male; Middle Aged

The Physicians' Routine Evaluation of Safety and Efficacy of NovoMix 30 Therapy (PRESENT) study was done to assess the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) in patients with type 2 diabetes mellitus in routine clinical practice.. This was a prospective, multicentric, multinational, observational study in type 2 diabetes patients. The patients were transferred to BIAsp 30 with or without oral antidiabetic drugs (OADs). We present the results of 6 months of treatment in the Indian cohort (n = 3559) with type 2 diabetes mellitus who were inadequately controlled on current treatment.. At three and six months, significant reductions from baseline were observed in the mean glycated haemoglobin (HbA1c) (-1.32% and -1.94%), fasting plasma glucose (-56.16 mg/dl and -75.24 mg/dl) and post-prandial plasma glucose (-88.74 mg/dl and -119.16 mg/dl) (p < 0.001). A significantly greater proportion of patients achieved target HbAlc of less than 7% at six months (31.1%), compared with baseline (3.1%), of which 70.4% did not report hypoglycaemia. The rate of total hypoglycaemia was reduced from 3.1 events per patient-year at baseline to 1.5 events per patient-year at end of the study. Episodes were mostly minor and diurnal. Except for two serious adverse drug reactions (ADRs) reported by one patient at 3 months, there were no reports of ADRs during the treatment period. More than 95% of patients and doctors were "very satisfied" or "satisfied" with BIAsp 30 treatment, compared to previous treatment.. The use of BIAsp 30 monotherapy or in combination with OADs in clinical practice was effective and safe in poorly controlled Indian type 2 diabetes patients. Both patients and doctors showed a high degree of treatment satisfaction.

Topics: Administration, Oral; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; India; Injections, Subcutaneous; Insulin; Insulin Aspart; Insulin, Isophane; Prospective Studies; Racial Groups; Treatment Outcome

An observational study in Saudi Arabia indicated that conversion to biphasic insulin aspart 30 (BIAsp 30) from human insulin (HI) was associated with improvement of glycaemic control.. A validated computer simulation model of diabetes was used to project long-term outcomes (such as quality-adjusted life expectancy and direct medical costs) based on patient characteristics and treatment effects observed in the Saudi Arabian PRESENT subgroup (n=598). Baseline prevalence of comorbidities was obtained from published sources. Primary research was performed in Riyadh and Jeddah to derive diabetes-related complication costs and patient management practices.. Conversion to BIAsp 30 from HI was projected to increase life expectancy by 0.62 years (11.77 +/- 0.20 vs. 11.15 +/- 0.19 years) and quality-adjusted life expectancy by 0.96 quality-adjusted life years (QALYs) (7.03 +/- 0.12 vs. 6.07 +/- 0.11 QALYs). Direct medical cost savings of Saudi Arabian Riyals (SAR) 53,879 per patient were projected for conversion to BIAsp 30 therapy (SAR 84,761 +/- 3102 vs. SAR 138,640 +/- 4102 per patient). Cost savings were driven by lower costs of hypoglycaemia (SAR 286 vs. SAR 57,437 per patient), and lower costs of renal complications (SAR 18,848 vs. SAR 31,228) over patient lifetimes.. Conversion to BIAsp 30 from HI was projected to improve life expectancy and quality-adjusted life expectancy while reducing lifetime direct medical costs.

Topics: Adult; Biphasic Insulins; Computer Simulation; Diabetes Complications; Diabetes Mellitus, Type 2; Glycemic Index; Health Care Costs; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Life Expectancy; Middle Aged; Outcome Assessment, Health Care; Saudi Arabia; Sensitivity and Specificity

Hypoglycemia is a common consequence of achieving tight glycemic control for patients with type 2 diabetes, with clinical effects ranging from occasional mild discomfort to incapacitation, coma, or in rare cases, death. Severe hypoglycemic events, particularly those resulting in emergency medical intervention or hospitalization, incur substantial medical costs for patients and the healthcare system. Although vigilance is needed for the possibility of severe events, hypoglycemia need not be a barrier to effective glycemic control in type 2 diabetes. Data from clinical trials and meta-analyses have demonstrated that the basal insulin analog insulin glargine results in a reduced rate of severe hypoglycemic events compared with conventional insulin therapy such as neutral protamine Hagedorn (NPH) insulin. Overall, use of insulin glargine compared with NPH insulin appears to reduce the risk of nocturnal and severe hypoglycemia by 40% to 60% and may result in cost savings. Analyses of hypoglycemia rates from "real-world" clinical practice databases and retrospective analyses of medical claims data also have revealed reduced rates with insulin glargine, consistent with the findings from clinical trials.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Insurance Claim Review; Medical Records Systems, Computerized; Meta-Analysis as Topic; Randomized Controlled Trials as Topic

Topics: Body Weight; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Exenatide; Glipizide; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin, Isophane; Metformin; Peptides; Pioglitazone; Thiazolidinediones; Venoms

Topics: Administration, Oral; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting

Topics: Administration, Oral; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glycated Hemoglobin; Half-Life; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

Topics: Administration, Oral; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Disease Progression; Edema; Humans; Hypoglycemic Agents; Inositol; Insulin, Isophane; Male; Middle Aged; Pericardial Effusion; Pleural Effusion; Sulfonylurea Compounds

To determine how young adults with insulin therapy manage daily care of diabetes during the physically demanding conditions of conscript military service, and to evaluate the effects of military service on glycaemic control and on the incidence of acute diabetic complications.. An observational study of 47 young male volunteer conscripts receiving insulin therapy was carried out at the Signal Regiment in Riihimäki from January 2001 to July 2005. Outcome measures were drop-out rate from service, management of diabetes care, glycaemic control, and occurrence of severe hypoglycaemia or ketoacidosis during service.. Forty (85%) diabetic conscripts completed service, with service time ranging from 180 to 362 days, and seven (15%) interrupted service. One-third of conscripts reported difficulties during military training with insulin injections and blood glucose testing. The mean HbA(1c) during service increased by 0.6% units (P = 0.007) from baseline. Five events of severe hypoglycaemia in three conscripts (overall incidence rate 0.15 per patient-year) and one ketoacidosis event occurred. Diabetic conscripts were chosen for leadership training more often than non-diabetic conscripts.. Our data suggest that selected and motivated adolescents on insulin therapy can manage the daily care of diabetes and maintain appropriate glycaemic control during service, although the risk of severe hypoglycaemia exists.

Topics: Adolescent; Adult; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Finland; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin, Isophane; Male; Military Personnel; Risk Factors

This case-control study was designed to analyse predictors of the effects on HbA1c levels in 4001 type 1 and type 2 diabetic patients after changing their insulin treatment. Patients from 15 outpatient diabetic clinics were treated with basal insulin and multiple injections of short-acting insulin. The effects on HbA1c of changing from NPH insulin to insulin glargine as basal insulin were studied, compared to patients continuing with NPH insulin. The following possible predictors were examined with multiple regression analysis: age, sex, type and duration of diabetes, smoking, metformin use, insulin requirement, number of basal doses per day, BMI and HbA1c at baseline. The difference between the two regression functions yielded the effect of switching treatment to insulin glargine compared to continuing with NPH insulin. Male gender, low BMI and high baseline HbA1c levels were significant predictors for a greater decrease in HbA1c when changing to insulin glargine. For example, for men with a BMI of 25 and an HbA1c of 8.0%, there was a calculated mean benefit in HbA1c of 0.26 percentage points by changing to insulin glargine, whereas women with a BMI 30 had no benefit of such a change. Thus, changing to insulin glargine had best effect in male patients with low BMI. This is one of the first studies designed to find responders to insulin treatment. Analyses of predictors may prove useful in order to tailor insulin treatment in diabetic patients in clinical practice. The clinical effects need to be confirmed in other studies and randomised controlled trials.

Topics: Body Mass Index; Case-Control Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Regression Analysis; Retrospective Studies; Sensitivity and Specificity; Sex Factors

Intensive insulin therapy improves glycosylated haemoglobin (Hb(A1C)) levels and delays the onset of long-term diabetes-related complications. Current treatment guidelines recommend maintaining a glycosylated haemoglobin (Hb(A1C)) of < or = 7% in patients with type 1 and 2 diabetes mellitus. However, the risk of hypoglycaemia increases with lower Hb(A1C) levels. As such, patients often choose to settle for suboptimal glucose control in order to prevent hypoglycaemic events. At a given Hb(A1C) level, treatment with insulin glargine results in a lower risk of hypoglycaemia in type 1 and 2 diabetes compared with NPH insulin. It has been proposed that the lower hypoglycaemic risk will allow more patients to achieve target Hb(A1C) levels with insulin glargine compared with NPH insulin. The objective of this study was to assess the cost effectiveness of insulin glargine compared with NPH insulin in patients with type 1 or 2 diabetes who had inadequate glycaemic control.. A long-term, state-transition model was developed to simulate the natural history of type 1 and 2 diabetes. Risks of diabetes-related macro- and microvascular complications and mortality by Hb(A1C) levels were estimated based on the UKPDS (United Kingdom Prospective Diabetes Study). Outcome measures included complication rates and associated costs, insulin costs, life years (LYs) and QALYs. The baseline analysis was conducted for patients with type 1 and 2 diabetes (aged 27 and 53 years, respectively) with Hb(A1C) levels >7%, using a 36-year time horizon and a Canadian public payer perspective. Costs and effects were discounted at 5% per annum. Univariate sensitivity analyses were performed on key model inputs. All costs were reported in $Can (2005 values).. The NPH insulin group had lower total costs than the insulin glargine group for patients with inadequately controlled diabetes (Hb(A1C) >7%; lifetime difference 1398 Can dollars and 1992 Can dollars, respectively, in type 1 and 2 diabetes). However, patients treated with insulin glargine had greater total and quality-adjusted life expectancy than those who received NPH insulin (incremental LY = 0.08 and QALYs = 0.07 in type 1 diabetes and incremental LY = 0.25 and QALYs = 0.23 in type 2 diabetes). The weighted incremental cost per LY gained and QALY gained were 18,661 Can dollars and 20,799 Can dollars, respectively, in type 1 diabetes and 8041 Can dollars and 8618 Can dollars, respectively, in type 2 diabetes (discounted results).. The cost-effectiveness ratios for insulin glargine use for type 1 and 2 diabetes provide evidence for its adoption from a Canadian healthcare payer perspective.

Topics: Analysis of Variance; Canada; Cost-Benefit Analysis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Treatment Outcome

The Predictable Results and Experience in Diabetes through Intensification and Control to Target: An International Variability Evaluation (PREDICTIVE) Study is a large, multi-centre, observational study assessing the safety and efficacy of insulin detemir in everyday clinical practice.. This subgroup analysis of the German cohort of PREDICTIVE evaluates over 3 months, patients with type 2 diabetes who were transferred to insulin detemir +/- oral antidiabetic drugs (OADs) from an OAD-only regimen (n = 1321), NPH insulin +/- OADs (n = 251) or insulin glargine +/- OADs (n = 260).. Among all groups, 3 months after starting treatment with insulin detemir, total, daytime and nocturnal hypoglycaemic events/patient were reduced by 84, 80 and 90%, respectively, from baseline. No major hypoglycaemic events were reported during treatment with insulin detemir. HbAlc was significantly reduced from baseline in each of the subgroups (-1.29,-0.60 and-0.59% for patients previously taking OADs only, NPH insulin +/- OADs and insulin glargine +/- OADs respectively; p < 0.0001), as was fasting blood glucose (FBG) (-58.1,-29.1 and-24.6 mg/dl; p < 0.0001) and FBG variability-8.2 mg/dl,-5.7 mg/dl; p < 0.0001 and -5.1 mg/dl; p = 0.0008). All subgroups combined lost an average of 0.9 kg of body weight (p < 0.0001) during the study. Total daily basal insulin dose increased slightly from baseline for those patients on a prior insulin regimen, and in this study 79% of patients used insulin detemir once daily.. These data confirm the short-term safety and efficacy of insulin detemir +/- OADs in a real-world scenario and support the findings of randomized controlled clinical trials with insulin detemir, including its limited effects on body weight.

Topics: Administration, Oral; Blood Glucose; Cohort Studies; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome; Weight Loss

The objective of this study was to evaluate the cost-effectiveness of insulin glargine compared with NPH insulin in patients with type 2 diabetes and in whom OAD (oral anti-diabetics) had failed in Switzerland.. Long-term diabetes outcomes were simulated with the Diabetes Mellitus Model (DMM) over a period of 10 years. The incidences of long-term complications (micro- and macrovascular events) were simulated for 10,000 patients over 10 years for six different scenarios. The scenarios were based on HbA1c reductions observed in clinical trials. For insulin glargine, HbA1c reductions of 0.96% (pessimistic case) and 1.24% (optimistic case) were simulated for three different HbA1c baseline values (10, 9 and 8%). For NPH insulin the HbA1c reduction was assumed to be 0.84%. A cost model and a utility model were developed in order to use the cumulated incidences of the simulations for the calculation of cost and QALYs (quality-adjusted life years). The unit costs of micro- and macrovascular events were assessed on the basis of published literature and guideline-projected resource-use estimations for Switzerland. Disutility values of diabetes-related long-term complications were derived from the literature. Total direct medical costs or QALYs were assessed by a combination of cumulated incidences of each event up to 10 years with the corresponding unit cost per event (in addition to the acquisition cost) or with disutility values per event, respectively. Events, total cost, and QALYs were discounted at 3%. In scenarios where no savings could be shown for insulin glargine, incremental cost-effectiveness ratios were calculated as the incremental cost per event prevented and the cost per QALY gained.. Cost comparison demonstrated that insulin glargine is the dominant strategy for the optimistic case scenario starting at a baseline HbA1c value of 10% as savings in the management of complications exceeded the difference in acquisition costs after 8 years of treatment. Optimistic case scenarios for baseline HbA1c values of 9 and 8% achieved costs per QALY gained amounting to CHF 2,853 and CHF 5,711 and costs per event prevented amounting to CHF 2,054 and CHF 4,899, respectively. Pessimistic case scenarios for baseline HbA1c values of 10, 9 and 8% resulted in costs per QALY gained amounting to CHF 40,441, CHF 45,701 and CHF 49,468 and costs per event prevented amounting to CHF 27,742, CHF 32,451 and CHF 41,620, respectively.. This study investigated the long-term health-economic implications of treating type 2 diabetes patients, in whom OAD had failed, with insulin glargine versus NPH insulin in Switzerland. The 10-year simulations demonstrated that the deltaHbA1c reductions of 0.4 and 0.12% achieved with insulin glargine led to a reduction of long-term complications, mortality and associated costs as well as to an improved quality of life. Insulin glargine proved to be cost-effective and represents good to excellent value for money compared to NPH insulin.

Topics: Aged; Computer Simulation; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Epidemiologic Methods; Female; Glycated Hemoglobin; Health Care Costs; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Quality of Life; Quality-Adjusted Life Years; Switzerland

Topics: Delayed-Action Preparations; Diabetes Mellitus, Type 2; Diagnosis, Differential; Drug Eruptions; Humans; Hypersensitivity, Immediate; Immunoglobulin E; Injections, Subcutaneous; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Insulin, Regular, Human; Intradermal Tests; Isophane Insulin, Human; Male; Middle Aged; Urticaria

Topics: Administration, Oral; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting

To assess and compare the efficacy and safety of insulin glargine as intensive replacement of basal insulin in Japanese patients with type 1 (n = 72) and type 2 (n = 46) diabetes, we switched their intensive insulin regimen from NPH plus regular or rapid-acting insulin to glargine plus bolus insulin, which included regular and rapid-acting insulin, and recorded changes in glycemic control and frequency of hypoglycemia for 18 months. The dose titration of basal and bolus insulin was based on home self-monitored blood glucose measurements and monthly HbA(1C). Mean HbA(1C) level was improved significantly at 3 months after switching to glargine plus bolus insulin regimen and these effects continued for 18 months in both type 1 and type 2 diabetes patients (HbA(1C) level: type 1: baseline 8.9 +/- 2.6%, 18 months 7.8 +/- 1.5% (p<0.05), type 2: baseline 8.2 +/- 2.6%, 18 months 7.7 +/- 1.5%. Body weight was slightly but significantly increased at 18 months only in type 2 diabetes. Total daily bolus insulin doses were not changed but basal insulin could be increased significantly after switching regimens in both types diabetes compared with baseline. The frequency of mild to moderate hypoglycemia (self-assisted episodes, blood glucose <70 mg/dl) was marginally lower with glargine but not significantly. Self-monitored fasting blood glucose level was significantly improved after switching in type 2 diabetes. Patients with the worst HbA(1C) level at baseline exhibited more than 10% improvement in HbA(1C) level after switching both type 1 and type 2 diabetes. The HbA(1C) levels of the effectively treated patients were comparable to those of ineffectively treated ones at 6 months and the same improvement was seen at 18 months. Our results suggested that insulin glargine is more effective than NPH insulin as intensive replacement of basal insulin, particularly in those Japanese patients with difficult glycemic control with NPH insulin, equally in both type 1 and type 2 diabetes.

Topics: Adult; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Japan; Longitudinal Studies; Male; Middle Aged; Prospective Studies

The Physician's Routine Evaluation of Safety and Efficacy of NovoMix* 30 Therapy (PRESENT) aims to assess the safety and efficacy of biphasic insulin aspart (BIAsp30) used in routine clinical practice.. This was a large, multi-national, multi-centre, prospective, 6-month study in type 2 diabetes mellitus patients who were prescribed BIAsp30. Efficacy endpoints included changes in HbA(1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPPG), and proportion who achieved target HbA(1c) < 7%. Changes from baseline were analysed using paired t-test. Safety endpoints were incidence and rate of hypoglycaemic episodes. A subgroup of patients previously uncontrolled (HbA(1c) > or = 7.0%) on biphasic human insulin (BHI) were analysed.. Glycaemia improved significantly (mean +/- SD): HbA(1c) by 1.58 +/- 1.69% points (from 9.32 +/- 1.64% to 7.70 +/- 1.29%), FPG by 2.92 +/- 3.71 mmol/L and PPPG by 4.75 +/- 4.87 mmol/L. The incidence of hypoglycaemic episodes decreased over time, from 38.7% (baseline) to 20.8% (6 months). Episodes were mostly minor (reduced from 37.7 to 20.6% at 6 months), occurring during the day (reduced from 31.5 to 17.1% at 6 months). Major episodes were less frequently reported (reduced from 5.0 to 0.4% at 6 months). The rate of hypoglycaemia (episodes/patient year) from baseline to end of study decreased over time for overall (8.9-2.2), major (0.7-0.1), minor (8.2-2.2) and nocturnal (2.9-0.5) episodes.. In this observational study, in the type 2 diabetes mellitus patients who were poorly controlled on BHI, glycaemia improved when transferred to BIAsp30, and a lower incidence or rate of hypoglycaemia was observed in these patients.

Topics: Aged; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Female; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Treatment Outcome

Combination therapy consisting of biphasic insulin aspart 30 bid with metformin provide better glycaemic control in obese patients with diabetes mellitus type 2. In our study, patients who were treated with 2550 mg of metformin, administered in three daily doses had poor glycaemic control. Three months after switching from metformin therapy to treatment with biphasic insulin aspart 30 + metformin twice a day, glycaemic control improved with significant reduction in hemoglobin HbA1c, fasting blood glucose and postprandial blood glucose levels. Biphasic insulin aspart 30 in combination with metformin administered twice a day may be recommended as a starting insulin treatment in obese diabetic persons whose glycaemic control remained poor while on oral metformin therapy alone.

Topics: Administration, Oral; Aged; Biphasic Insulins; Diabetes Mellitus, Type 2; Female; Humans; Hyperglycemia; Insulin; Insulin Aspart; Insulin, Isophane; Insulin, Long-Acting; Male; Metformin; Middle Aged; Obesity; Treatment Outcome

Topics: Adult; Aged; Aged, 80 and over; Body Mass Index; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin, Isophane; Male; Middle Aged; Recombinant Proteins; Treatment Outcome

This observational study in patients with type 2 diabetes failing oral agent therapy with or without basal insulin was conducted to assess whether addition and self-titration of biphasic insulin aspart 70/30 (BIAsp 30) could achieve American Association of Clinical Endocrinologists (AACE)/International Diabetes Federation (IDF) and American Diabetes Association (ADA) glycemic targets (HbA(1c)< or =6.5 and <7%).. Enrolled patients (n = 100, HbA(1c)> or =7.5 and < or =10%) were > or =18 years of age, had diabetes > or =12 months and had received a stable antidiabetic regimen for at least 3 months [minimum of two oral antidiabetic drugs (OADs) or at least one OAD plus once-daily basal insulin < or =60 U]. Patients discontinued prior basal insulin and added one injection of BIAsp 30 (12 U or 70-100% of prior basal insulin dose within 15 min of dinner initiation). Patients self-titrated their BIAsp 30 dose with investigator guidance every 3 or 4 days to achieve pre-breakfast fasting blood glucose (FBG) of 80-110 mg/dl. At 16 weeks, a pre-breakfast injection of 6 U of BIAsp 30 was added if week 15 HbA(1c) exceeded 6.5%; the added dose was titrated to achieve pre-dinner BG of 80-110 mg/dl. After an additional 16 weeks, 3 U of pre-lunch BIAsp 30 was added if HbA(1c) exceeded 6.5%. This added dose was adjusted based on 2-h post-lunch BG to achieve postprandial glucose of 100-140 mg/dl. Subjects achieving an HbA(1c)< or =6.5% at 15 and 31 weeks completed the study at weeks 16 and 32 respectively.. Addition of once-daily BIAsp 30 before dinner enabled 21% of the patients to achieve AACE and IDF targets (HbA(1c)< or =6.5%) and 41% to achieve ADA targets (HbA(1c) <7%). With two daily injections of BIAsp 30, these glycaemic goals were achieved by 52 and 70% of subjects. With three daily BIAsp 30 injections, 60% of patients achieved HbA(1c)< or =6.5%, and 77% achieved HbA(1c) <7.0%.. This clinical trial demonstrates that initiation of once-daily BIAsp 30 to type 2 diabetes patients poorly controlled on various OAD regimens was an effective treatment approach for achieving glycaemic goals. Additional patients safely achieved these goals by increasing the number of BIAsp 30 injections from one to two, and then, if uncontrolled, from two to three doses per day. Eventually, most patients previously uncontrolled on OADs with or without basal insulin were controlled by the addition and vigorous titration of BIAsp 30 to oral agent therapy.

Topics: Administration, Oral; Biphasic Insulins; Blood Glucose; Blood Glucose Self-Monitoring; Cholesterol; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections; Insulin; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Postprandial Period; Treatment Outcome

We previously reported that lipoprotein lipase mass level in preheparin serum (preheparin LPL mass) was significantly lower in type 2 diabetes mellitus compared to healthy subjects and increased by conventional insulin therapy using NPH (intermediate-acting) insulin. The aim of this study was to investigate the effects of intensive insulin therapy on preheparin LPL mass. Thirty-two subjects (total group) with type 2 diabetes receiving treatment by NPH insulin injection twice a day in the morning and evening were switched to basal bolus insulin (BBI) therapy (fast-acting insulin after each meal and NPH insulin before bedtime). In 14 subjects, the total daily insulin dose was not change after switching to BBI therapy (iso-dose group). After 3 months of BBI therapy, preheparin LPL mass increased significantly from 47 to 56 ng/ml in total group. Glycosylated hemoglobin and serum triglyceride levels decreased significantly, and high-density lipoprotein-cholesterol increased significantly. Low-density lipoprotein levels did not changed but increase in size was suggested by PAG disc electrophoresis. Similar changes were observed in the iso-dose group. These results suggest that BBI therapy enhances preheparin LPL mass, accompanied by antiatherogenic changes in glucose and lipid metabolism.

Topics: Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin, Isophane; Lipids; Lipoprotein Lipase; Male; Middle Aged

Fifty-seven type 2 diabetic patients with metabolic syndrome and on insulin were assessed by a paired analysis before and 6 months after addition of metformin as combination therapy to evaluate the impact of the association on glycemic control, blood pressure, and lipid profile. This was a historical cohort study in which the files of type 2 diabetic patients with metabolic syndrome on insulin were reviewed. The body mass index (BMI), waist circumference, lipid profile, A1C level, fasting blood glucose level, daily dose of NPH insulin, systolic blood pressure, and diastolic blood pressure were assessed in each patient before the start of metformin and 6 months after the initiation of combination therapy. Glycemic control significantly improved (P < 0.001) after the addition of metformin (1404.4 +/- 565.5 mg/day), with 14% of the 57 patients reaching A1C levels up to 7%, and 53% reaching values up to 8%. There was a statistically significant reduction (P < 0.05) of total cholesterol (229.0 +/- 29.5 to 214.2 +/- 25.0 mg/dL), BMI (30.7 +/- 5.4 to 29.0 +/- 4.0 kg/m2), waist circumference (124.6 +/- 11.7 to 117.3 +/- 9.3 cm), and daily necessity of insulin. The reduction of total cholesterol occurred independently of the reductions of A1C (9.65 +/- 1.03 to 8.18 +/- 1.01%) and BMI and the reduction of BMI and WC did not interfere with the improvement of A1C. In conclusion, our study showed the efficacy of the administration of metformin and insulin simultaneously without negative effects. No changes were detected in HDL-cholesterol or blood pressure.

Topics: Blood Glucose; Blood Pressure; Body Mass Index; Cohort Studies; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Humans; Hypoglycemic Agents; Insulin, Isophane; Lipids; Male; Metabolic Syndrome; Metformin; Middle Aged; Treatment Outcome

Topics: Biphasic Insulins; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Health Care Costs; Humans; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Randomized Controlled Trials as Topic; Treatment Outcome

A 6-8-fold higher insulin-like growth factor 1 (IGF-1) receptor binding affinity in vitro is reported for the insulin analogue glargine compared with human insulin. This study evaluates the in vivo significance by exploring the growth hormone (GH)-IGF-1 axis. Assuming a higher binding affinity of insulin glargine to pituitary IGF-1 receptors, serum IGF-1 concentrations should decrease via negative feedback.. In a crossover study, insulin glargine or NPH insulin, respectively, were used in identical doses as basal insulins in treatment periods of 3 weeks.. Overall glycaemic control was not different between the treatment regimens. In contrast to the hypothesis, serum IGF-1 concentrations were higher during insulin glargine treatment compared with NPH insulin in patients with Type 1 diabetes (177 +/- 18 vs. 159 +/- 18 microg/l, P < 0.02, n = 17, age 28 +/- 2 years). The effect on IGF-1 was most pronounced in male patients with Type 1 diabetes (174 +/- 11 vs. 146 +/- 10 microg/l, P < 0.02, n = 10), but was not significant in patients with Type 2 diabetes (92 +/- 9 vs. 86 +/- 8 microg/l, NS, n = 25, age 66 +/- 2 years).. In contrast to our hypothesis, serum IGF-1 did not decrease, but rose during insulin glargine treatment, suggesting an absence of relevant IGF-1-like activity of glargine at the level of the pituitary. Improved plasma glucose at dawn during glargine treatment may intensify growth hormone surges and increase IGF-1 synthesis. Significant increases were seen in younger patients, compatible with the higher activity of the GH-IGF-1 axis in this age group.

Topics: Adult; Aged; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged

Topics: Clinical Trials, Phase IV as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Disease Progression; Humans; Insulin; Insulin Glargine; Insulin-Like Growth Factor I; Insulin, Isophane; Insulin, Long-Acting; Retinal Diseases; Retinal Vessels; United States; United States Food and Drug Administration; Vascular Endothelial Growth Factor A

We studied a systematic program to reeducate our medical house officers on how to manage inpatient hyperglycemia without the use of sliding-scale insulin (SSI).. Patients admitted to the general medical service with diabetes or a blood glucose >140 mg/dl were included. HbA(1c) was measured in all patients, and therapy was modified if the HbA(1c) was >7.0%. For each 24 h on call, two house officers were responsible for all glucose management for their team's patients and rounded with a teaching endocrinologist twice daily for 2 weeks. Oral agent or insulin therapy was modified using blood glucoses and HbA(1c). All patients who required insulin therapy were treated with basal and bolus insulin, usually NPH and regular, adjusted twice daily.. During 8 weeks, 88 patients were identified and 16 house officers were instructed. The mean duration of diabetes was 10.4 years. Mean HbA(1c) level was 8.7%, and 48% of patients had HbA(1c) >8%. All patients with HbA(1c) >7% had diabetes therapy intensified. Overall 80% had their diabetes therapy changed by discharge. Compared with 98 historical control subjects, significantly fewer study patients had episodes of hyperglycemia, and a subgroup followed for 12 months showed a decrease in HbA(1c) from 10.1 to 8%.. Medical history, blood glucose, and HbA(1c) testing can effectively identify patients with inpatient hyperglycemia. Using direct ward-based teaching and a widely disseminated pocket set of guidelines, house officers can be taught to effectively and safely manage inpatient hyperglycemia without the use of SSI.

Topics: Adult; Aged; Aged, 80 and over; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Education, Medical, Graduate; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; Inpatients; Insulin; Insulin, Isophane; Male; Medical Staff, Hospital; Middle Aged; Staff Development

The purpose of this study was to compare the effect of insulin glargine (glargine) and NPH insulin (NPH) on long-term outcomes in type 2 diabetes patients using the Diabetes Mellitus Model (DMM).. The DMM predicts short- and long-term complications over ten years using data in studies published previously. The main effect on outcome is the influence of the treatment on the HbA1c level which is simulated over time. The simulation was based on a cohort size of 10,000 type 2 diabetes patients taking either glargine or NPH. The best scenario, baseline scenario and worst case scenario were simulated based on differences of 0.13%, 0.44% and 0.85%, respectively, in HbA1c values and corresponding to potentially attainable improvements with comparable or lower hypoglycemia rates in glargine-treated patients and NPH-treated patients. Assumptions for scenarios 1, 2 and 3 were based on a regression analysis of clinical trial data (pooled data clinical trials comparing glargine and NPH) in which the effect of glargine on the HbA1c/hypoglycemia incidence ratio was superior to that of NPH.. The relative risks (RR, glargine/NPH) obtained for scenarios 1, 2 and 3 were 0.97, 0.89 and 0.81, respectively, for long-term microvascular complications and 0.99, 0.95 and 0.91, respectively, for long-term macrovascular complications. RR reductions ranged from 1% in the less optimistic scenario to > 20% in the "best case" scenario. Sensitivity analyses showed that variations in the mean baseline HbA1c values and duration of the diabetes were without effect on these outcomes.. Although there is a need to corroborate the results of these simulations with real, long-term clinical data, they have demonstrated that, assuming comparable or lower rates of hypoglycemia, a better glycemic control (HbA1c reduction) can be expected with glargine when compared to NPH together with a reduction in long-term complications, mortality and associated costs.

Topics: Computer Simulation; Diabetes Mellitus, Type 2; Epidemiologic Methods; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Sensitivity and Specificity

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Education, Medical, Graduate; Humans; Hypoglycemic Agents; Inpatients; Insulin; Insulin, Isophane; Medical Staff, Hospital

To evaluate the long-term clinical and cost outcomes associated with biphasic insulin aspart 30/70 (BIAsp 30/70, premixed 30% soluble and 70% protaminated insulin aspart in one injection) compared to insulin glargine treatment in insulin-naïve type 2 diabetes patients failing oral antidiabetic agents in the UK, based on findings recently reported from the INITIATE clinical trial.. The CORE Diabetes Model, a published, peer-reviewed and validated model of diabetes, was used to evaluate life expectancy, quality-adjusted life expectancy, cumulative incidence of complications and direct medical costs over patient lifetimes. The model simulates the range of diabetic complications and disease progression within a series of sub-models (cardiovascular disease, neuropathy, renal and eye disease) based on published data. Baseline cohort characteristics (54.5% male, mean age 52.45 years, mean diabetes duration 9 years, mean HbA(1c) 9.77%) and treatment effects were based on INITIATE. Costs were derived from published UK sources. The analysis was run over a 35-year time horizon (patient lifetime) from a third party payer perspective. Costs and clinical benefits were discounted at 3.5% per annum. Sensitivity analyses were performed.. BIAsp 30/70 was associated with projected improvements in discounted life expectancy (0.19 +/- 0.20 years) and quality-adjusted life expectancy (0.19 +/- 0.14 quality-adjusted life years [QALYs]), as well as a reduced incidence of retinopathy and nephropathy complications, versus glargine. Total lifetime direct costs were 1319 pounds higher with BIAsp 30/70 than with glargine leading to an incremental cost-effectiveness ratio of 6951 pounds per QALY gained.. This study is the first to address the long-term health economic implications of treating type 2 diabetes patients failing oral anti-diabetics with a biphasic insulin mix versus long-acting insulin. Our projections indicate that improved HbA1c levels with BIAsp 30/70 treatment are associated with improvements in life expectancy and quality-adjusted life expectancy, and that BIAsp 30/70 represents excellent value for money compared to insulin glargine in the UK.

Topics: Adult; Aged; Biphasic Insulins; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Health Care Costs; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Life Expectancy; Male; Middle Aged

Topics: Biphasic Insulins; Blood Glucose; Chemistry, Pharmaceutical; Diabetes Mellitus, Type 2; Drug Delivery Systems; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane

Topics: Diabetes Mellitus, Type 2; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Sulfonylurea Compounds

Topics: Diabetes Mellitus, Type 2; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Research Design; Sulfonylurea Compounds

In the last few years short-acting insulin analogs have become increasingly popular. Their introduction has unmasked serious deficiencies in the capacity of isophane insulin to provide a stable basal insulinaemia. The long-acting insulin analogs, insulin glargine and insulin detemir, have been developed as alternatives to isophane insulin. Insulin glargine has a long duration of action and has demonstrated its usefulness in diabetes type 2, specifically a lower incidence of (nocturnal) hypoglycaemia compared to isophane insulin, in clinical practice. Insulin detemir has a very low variability in absorption and also seems to reduce the risk of nocturnal hypoglycaemia in diabetes type 1. More studies are, however, needed. Because of the higher costs of these novel insulins, the decision to switch a patient from isophane insulin to an insulin analog has to be made on an individual basis.

Topics: Blood Glucose; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

Topics: Diabetes Mellitus, Type 2; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Treatment Outcome

Topics: Diabetes Mellitus, Type 2; Drug Administration Schedule; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

A rare case of diabetic patient who developed multiple cutaneous hyperpigmented spots following bovine isophane (NPH) insulin injection is described here.

Topics: Adult; Diabetes Mellitus, Type 2; Drug Eruptions; Humans; Hypoglycemic Agents; Insulin, Isophane; Male

Topics: Aged; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Sulfonylurea Compounds

Topics: Diabetes Mellitus, Type 2; Drug Administration Schedule; Heart Rate; Humans; Insulin, Isophane; Myocardial Infarction; Survival Rate

Topics: Biphasic Insulins; Diabetes Mellitus, Type 2; Drug Combinations; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane

In recent years, the approach to the insulin treatment of type 2 diabetics has undergone a change. Age and clinical status of the patient are decisive determinants for the selection of the appropriate form of treatment. The therapeutic strategy aims to achieve insulin substitution matched to the therapeutic objective, that is, continuous monitoring should be carried out to enable adaptation of the form and intensity of treatment to meet the target end point HbA1c < 6.5%. This necessity results in the earlier use of insulin in all, not only obese, type 2 diabetics. As a compromise solution, a certain percentage of these diabetics will have to be satisfied with simpler forms of insulin substitution and a higher HbA1c value. Attention is drawn to the other parameters of the metabolic syndrome, such as blood pressure, weight, and lipid metabolism. Particular importance attaches to non-pharmacological measures, in particular with the aim of avoiding a further increase in weight due to the treatment with insulin.

Topics: Combined Modality Therapy; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diet, Diabetic; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Obesity; Patient Education as Topic

It was decided to demonstrate by the present observations to which extent beneficial long-term effects on metabolic control, body weight and microalbuminuria can be attained by applying intensive insulin therapy (IIT) to type 2 diabetic patients, particularly when using insulin lispro.. In our observational study, clinical data were evaluated during 6, 12 and 36 months after participation in our structured inpatient insulin treatment and teaching programme in 25 patients with conventional insulin therapy (CT), in 10 patients with IIT using human normal insulin and in 15 patients with IIT using insulin lispro who all could be followed for 3 years in our outpatient diabetic clinic.. In the CT-treated patients, HbA1c decreased from 10.2 +/- 0.4% to 7.6 +/- 0.2% (average +/- SEM) after 3 years. Body weight increased from 27.8 +/- 0.9 kg/m2 to 28.6 +/- 0.9 kg/m2, insulin dose increased from 29 +/- 3 U/day to 48 +/- 5 U/day (all p < 0.05), urinary albumin concentration was only transiently reduced. In the IIT-treated patients using human normal insulin, HbA1c fell from 10.6 +/- 0.8% to 7.9 +/- 0.5%, body weight increased from 27.8 +/- 1.4 kg/m2 to 29.8 +/- 1.3 kg/m2, urinary albumin concentration was reduced from 26 +/- 10 mg/l to 13 +/- 3 mg/l (all p < 0.05). Insulin dose increased only slightly from 57 +/- 6 U/day to 63 +/- 7 U/day. In the IIT-treated patients using insulin lispro HbA1c fell from 8.4 +/- 0.5% to 6.7 +/- 0.3%, body weight increased from 27.6 +/- 1.0 kg/m2 to 28.7 +/- 1.3 kg/m2, insulin dose from 36 +/- 5 U/day to 50 +/- 7 U/day, urinary albumin concentration was reduced from 23 +/- 4 mg/l to 13 +/- 4 mg/l (all p < 0.05). Blood pressure remained uninfluenced by insulin therapy.. In our patients, we observed a beneficial long-term effect on metabolic control of IIT-treatment using insulin lispro, which was evident over the complete 3-year observation period, together with an only moderate increase in insulin dose and a clinically acceptable increase in body weight, but a remarkable reduction of microalbuminuria. Thus, clinical outcome was superior to that in patients treated with CT or IIT using human normal insulin.

Topics: Aged; Albuminuria; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Lispro; Insulin, Isophane; Kidney Function Tests; Male; Metformin; Middle Aged; Treatment Outcome

Topics: Aged; Blood Glucose; Carbamates; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Humans; Hypoglycemic Agents; Insulin, Isophane; Male; Middle Aged; Piperidines

Topics: Adult; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Glycosuria; Humans; Hypoglycemic Agents; Insulin, Isophane; Male; Middle Aged; Postprandial Period

Topics: Aged; Alanine Transaminase; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Insulin; Insulin, Isophane; Liver; Liver Function Tests; Male; Metformin

A retrospective analysis was conducted to determine the effects of metformin on glycosylated hemoglobin (HbA1c), body weight, and adverse events in an African-American population. Thirty-six patients who were receiving combination therapy with metformin and either a sulfonylurea or insulin were identified from a hospital pharmacy database. Nineteen patients met the criteria for efficacy analysis. The combination of metformin with either a sulfonylurea or insulin resulted in a decrease of the average HbA1c from a baseline of 10.07% to 7.92% (delta = 2.15%). The effect of combination therapy on weight was variable; however, twice as many patients lost weight compared with those who gained weight. Metformin appeared to be well-tolerated, with gastrointestinal symptoms being the most commonly reported adverse events.

Topics: Adult; Aged; Aged, 80 and over; Black People; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glipizide; Glyburide; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin, Isophane; Male; Metformin; Middle Aged; Prognosis; Retrospective Studies

Topics: Administration, Oral; Adolescent; Adult; Aged; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin, Isophane; Male; Patient Education as Topic

In the past decade, human insulins have been substituting animal insulins, offering the advantage of its lesser antigenic capacity. One of the most clinically important problems with human NPH insulins is its tendency to flocculate. We present four diabetic patients who, after using flocculated human NPH insulin, encountered a deterioration in the metabolic control of their diabetes, and in two of them, there were bouts of diabetic Ketoacidosis "without any other apparent causal factors". Among those causes favoring flocculation are movement during transport, high temperatures, and probably leaving the vial open for an excessively long period of time, as with the extraction of multiple doses. Physicians, educators, diabetics, and their relatives should be informed of this phenomenon. Diabetics, especially those who carry insulin with them, should carefully inspect their vials before each injection to detect signs of flocculation.

Topics: Adult; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Flocculation; Humans; Insulin, Isophane; Male; Middle Aged

To evaluate the possible benefits of the addition of intermediate-acting insulin administered at bedtime to therapy with daytime sulfonylureas in patients with non-insulin-dependent diabetes mellitus for whom maximal doses of oral hypoglycemic agents have not been successful.. Study subjects were 16 consecutive obese patients aged from 44 to 78 years (mean age, 62 years) with histories of non-insulin-dependent diabetes mellitus for a mean of 9 years. None of the subjects had been able to control their diabetes with maximal doses of oral hypoglycemic agents. All patients received 20 mg glipizide or 10 mg glyburide twice a day, as well as education about the American Diabetes Association diet. Neutral protamine Hagedorn (NPH) insulin was empirically added in doses from 0.1 to 0.2 units/kg given at bedtime. The dose was adjusted on the basis of fasting blood glucose levels.. Mean fasting blood glucose decreased from 13.7 +/- 3.4 to 8.3 +/- 2.7 mmol/L at 3 months and 7.3 + 2.0 mmol/L at 1 year. Glycosylated hemoglobin decreased from 9.0% +/- 1.9% to 6.2% +2- 1.16% at 3 months and 6.3% +/- 1.22% at 1 year.. A late-night dose of NPH insulin was added to a regimen of daytime sulfonylureas in a group of obese patients with type II diabetes whose hyperglycemia was not controlled with maximal doses of oral hypoglycemic agents. This treatment proved to be beneficial and is a useful alternative to conventional insulin therapy in this group of patients.

Topics: Adult; Aged; Diabetes Mellitus; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glipizide; Glyburide; Humans; Insulin, Isophane; Middle Aged; Obesity; Prospective Studies; Time Factors

Topics: Administration, Oral; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Insulin; Insulin, Isophane

Premixing short- and intermediate-acting insulins in one syringe, with refrigerated storage before injection, is practised by some centres in the treatment of older patients with non-insulin-dependent diabetes. Because other studies have reported the loss of the short-acting insulin component after mixing with intermediate-acting insulins, we examined the clinical effect of mixing soluble insulin with lente or isophane insulins in subjects with non-insulin-dependent diabetes. When soluble and lente insulins were mixed in the same syringe and injected immediately, the peak level of insulin was very similar to the peak level after separate injections but occurred at five hours instead of three hours after the injection. As a result, the plasma free-insulin profile over three hours was lower with premixed insulin than after separate injections of the two insulins (incremental insulin area, 88 +/- 20 mU.L-1.h, and 129 +/- 37 mU.L-1.h, respectively; P less than 0.05). This delay in the absorption of soluble insulin caused a greater rise in plasma glucose levels such that the incremental glucose area over eight hours was 25.5 +/- 4.4 mmol.L-1.h for premixed insulin compared with 10.4 +/- 6.2 mmol.L-1.h for separate injections (P less than 0.05). Soluble and isophane insulins had similar absorption profiles whether injected separately or premixed (incremental insulin area, 0 to 3 h, 176 +/- 44 mU.L-1.h and 156 +/- 29 mU.L-1.h, respectively). Our results indicate that the absorption of soluble insulin is delayed when it is mixed with lente insulin but not with isophane insulin. Even in subjects with endogenous insulin secretion, this effect may have clinical importance and should be taken into account when insulin therapy is adjusted for patients with non-insulin-dependent diabetes.

Topics: Absorption; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Drug Combinations; Drug Evaluation; Female; Humans; Insulin; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Solubility; Time Factors

Mixtures of short-acting and intermediate-acting insulins often represent an effective regimen to achieve near-normal blood glucose values, yet controversy exists concerning the stability and predictability of such mixtures. In a study of diabetic patients, the biologic activity of a specific intermediate-acting insulin (insulatard) and a short-acting insulin (Velosulin) premixed in a 70:30 ratio was reproducible at three intervals and was stable for a period of up to three months. The serum levels of free insulin and the rate of onset and extent of the blood glucose lowering effects were not altered, showed two distinct peaks, and were comparable to those experienced with separate injections of equivalent doses of the intermediate-acting and short-acting insulins.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Combinations; Drug Evaluation; Drug Stability; Humans; Insulin; Insulin, Isophane; Middle Aged

Topics: Aged; Aged, 80 and over; Blood Glucose; Diabetes Mellitus, Type 2; DNA, Recombinant; Eating; Female; Humans; Insulin; Insulin, Isophane; Male; Middle Aged