insulin-detemir 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

Performing an updated meta-analysis to compare the safety and efficacy of insulin glargine and insulin detemir in adults with type 1 and type 2 diabetes.. Electronic databases were searched up to 18 August 2021. A random-effects model was applied to pool data from included studies to calculate the standardized mean differences (SMDs) for the continuous variables and relative risks (RRs) for the dichotomous variable.. Nine studies compared insulin detemir and insulin glargine in type 2 diabetes and three studies in patients with type 1 diabetes. The pooled SMD of weight gain was -0.59 (95% CI -1.05 to -0.14; P=0.01; I. It was found that there is no clinically considerable difference between the impacts of insulin detemir and insulin glargine in diabetic patients. The only statistically significant differences were less weight gain in type 2 diabetes and fewer episodes of severe hypoglycemia in type 1 diabetes with insulin detemir.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Weight Gain

The goal of this study was to compare the efficacy and tolerability of insulin degludec with those of other long-acting insulin analogues (insulin glargine and insulin detemir) in patients with type 1 or 2 diabetes mellitus (T1D or T2D).. Those randomized controlled trials comparing insulin degludec with other long-acting insulin analogues in the treatment of patients with T1D or T2D published on or before August 21, 2022, were retrieved from PubMed, Web of Science, the Cochrane Library, and EMBASE. The efficacy end points were the changes from baseline in hemoglobin A. Data from a total of 20 trials (19,048 patients) were included. The differences in the reductions in glycosylated hemoglobin between insulin degludec and other long-acting basal insulin analogues (insulin glargine and insulin detemir) used for the treatment of patients with T1D or T2D were not significant. However, the reduction in FPG was greater with insulin degludec (-0.370 mmol/L; 95% CI, -0.473 to -0.267 mmol/L; P ≤ 0.001). Throughout the treatment periods of all of the available trials, the estimated rate ratios of overall and nocturnal hypoglycemia were significantly decreased with insulin degludec compared with insulin glargine or insulin detemir in patients with T1D or T2D; the differences in the risks for severe hypoglycemia were not significant.. Compared with other long-acting insulin analogues (insulin glargine and insulin detemir), insulin degludec was associated with a significantly decreased FPG, with lower prevalences of overall and nocturnal hypoglycemia.

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

Many patients with type 2 diabetes will ultimately require the inclusion of basal insulin in their treatment regimen. Since most people with type 2 diabetes are managed in the community, it is important that primary care providers understand and correctly manage the initiation and titration of basal insulins, and help patients to self-manage insulin injections. Newer, long-acting basal insulins provide greater stability and flexibility than older preparations and improved delivery systems. Basal insulin is usually initiated at a conservative dose of 10 units/day or 0.1-0.2 units/kg/day, then titrated thereafter over several weeks or months, based on patients' self-measured fasting plasma glucose, to achieve an individualized target (usually 80-130 mg/dL). Through a shared decision-making process, confirmation of appropriate goals and titration methods should be established, including provisions for events that might alter scheduled titration (e.g. travel, dietary change, illness, hospitalization, etc.). Although switching between basal insulins is usually easily accomplished, pharmacokinetic and pharmacodynamic differences between formulations require clinicians to provide explicit guidance to patients. Basal insulin is effective long-term, but overbasalization (continuing to escalate dose without a meaningful reduction in fasting plasma glucose) should be avoided.Key messagesPrimary care providers often initiate basal insulin for people with type 2 diabetes.Basal insulin is recommended to be initiated at 10 units/day or 0.1-0.2 units/kg/day, and doses must be titrated to agreed fasting plasma glucose goals, usually 80-130 mg/dL. A simple rule is to gradually increase the initial dose by 1 unit per day (NPH, insulin detemir, and glargine 100 units/mL) or 2-4 units once or twice per week (NPH, insulin detemir, glargine 100 and 300 units/mL, and degludec) until FPG levels remain consistently within the target range. If warranted, switching between basal insulins can be done using simple regimens.The dose of basal insulin should be increased as required up to approximately 0.5-1.0 units/kg/day in some cases. Overbasalization (continuing to escalate dose without a meaningful reduction in fasting plasma glucose) is not recommended; rather re-evaluation of individual therapy, including consideration of more concentrated basal insulin preparations and/or short-acting prandial insulin as well as other glucose-lowering therapies, is suggested.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Primary Health Care

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

To review evidence comparing benefits and harms of long-acting insulins in patients with type 1 and 2 diabetes.. MEDLINE and two Cochrane databases were searched during February 2018. Two authors selected studies meeting inclusion criteria and assessed their quality. Comparative studies of adult or paediatric patients with diabetes treated with insulin degludec, detemir or glargine were included. Meta-analysis was used to combine results of similar studies, and the I. Of 2534 citations reviewed, 70 studies met the inclusion criteria. No statistically significant differences in HbA1c were seen between any two insulins or formulations. Hypoglycaemia was less probable with degludec than with glargine, including nocturnal hypoglycaemia in type 1 (rate ratio 0.68, 95% CI 0.56-0.81) and type 2 diabetes (rate ratio 0.73, 95% CI 0.65-0.82), and severe hypoglycaemia in type 2 diabetes (relative risk 0.72, 95% CI 0.54-0.96). Patients with type 2 diabetes had higher rates of withdrawal because of adverse events when treated with detemir compared with glargine (relative risk 2.1, 95% CI 1.4-3.3). Adults taking detemir gained about 1 kg less body weight than those taking degludec (type 1) or glargine (type 2).. No differences in glycaemic control were seen between insulin degludec, detemir and glargine. Hypoglycaemia was less probable with degludec than glargine, and patients taking detemir gained less body weight than those given degludec or glargine. In type 2 diabetes, withdrawals as a result of adverse events were more probable with detemir than glargine.

Topics: Blood Glucose; Comparative Effectiveness Research; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Treatment Outcome; Weight Gain

Since the introduction of insulin as a life-saving agent for patients with type 1 diabetes, insulin preparations have evolved to approximate physiologic insulin delivery profiles to meet prandial and basal insulin needs. While prandial insulins are designed to have quick time-action profiles that minimize postprandial glucose excursions, basal insulins are designed to have a protracted time-action profile to facilitate basal glucose control over 24 h. Given that all insulins have the same mechanism of action at the target tissue level, the differences in time-action profiles are achieved through different mechanisms of protraction, resulting in different behaviors in the subcutaneous space and different rates of absorption into the circulation. Herein, we evaluate the differences in basal insulin preparations based on their differential mechanisms of protraction, and the resulting clinical action profiles. Multiple randomized control trials and real-world evidence studies have demonstrated that the newer second-generation basal insulin analogs, insulin glargine 300 units/mL and insulin degludec 100 or 200 units/mL, provide stable glycemic control with once-daily dosing and are associated with a reduced risk of hypoglycemia compared with previous-generation basal insulin analogs insulin glargine 100 units/mL and insulin detemir. These advantages can lead to decreased healthcare resource utilization and cost. With this collective knowledge, healthcare providers and payers can make educated and well-informed decisions when determining which treatment regimen best meets the needs of each individual patient.Funding: Sanofi US, Inc.

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

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

Basal insulin analogues aim for protracted glycemic control with minimal adverse effects.. To assess the comparative efficacy and safety of basal insulin analogues for adults with type 2 diabetes mellitus (T2DM).. Several databases from inception to April 2018 without language restrictions, ClinicalTrials.gov to April 2018, references of reviews, and meeting abstract books.. Randomized trials lasting at least 12 weeks that compared efficacy (change in hemoglobin A1c [HbA1c] level from baseline [primary outcome]; percentage of patients with HbA1c level <7% at end of study and change in body weight [secondary outcomes]) and safety (hypoglycemia) of basal insulin analogues.. Two authors independently extracted data and assessed risk of bias for each outcome. All authors evaluated overall confidence in the evidence.. Thirty-nine trials (26 195 patients) assessed 10 basal insulin analogues. Low- to very-low-quality evidence indicated that thrice-weekly degludec (Deg-3TW) was inferior to most other regimens for reducing HbA1c level, with mean differences ranging from 0.21% (vs. degludec, 100 U/mL [Deg-100]) to 0.32% (vs. glargine, 300 U/mL [Glar-300]). High- to moderate-quality evidence suggested that detemir had a favorable weight profile versus all comparators, and Glar-300 was associated with less weight gain than glargine, 100 U/mL (Glar-100); Deg-100; degludec, 200 U/mL (Deg-200); Deg-3TW; and LY2963016. Low- and very-low-quality evidence suggested that Deg-100, Deg-200, and Glar-300 were associated with lower incidence of nocturnal hypoglycemia than detemir, Glar-100, LY2963016, and neutral protamine lispro (NPL). Incidence of severe hypoglycemia did not differ among regimens, except NPL, which was associated with increased risk versus Deg-100, detemir, Glar-100, and Glar-300.. Results are based mostly on indirect comparisons. Confidence in summary estimates is low or very low due to individual-study limitations, imprecision, or inconsistency.. Low-quality evidence suggests that basal insulin analogues for T2DM do not substantially differ in their glucose-lowering effect. Low- and very-low-quality evidence suggests some regimens may be associated with lower risk for nocturnal hypoglycemia (Deg-100, Deg-200, and Glar-300) or less weight gain (detemir and Glar-300).. None. (PROSPERO: CRD42016037055).

Topics: Adult; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Network Meta-Analysis; Risk Assessment

Since 2005, several glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been approved to treat people with type 2 diabetes. These agents are considered for use at the same point in the treatment paradigm as basal insulins. A comprehensive comparison of these drug classes, therefore, can help inform treatment decisions. This systematic review and meta-analysis assessed the clinical efficacy and safety of GLP-1 RAs compared with basal insulins.. MEDLINE, EMBASE, CENTRAL and PubMed databases were searched. Randomized clinical trials (RCTs) of ≥16 weeks' duration comparing GLP-1 RAs vs basal insulins in adults with type 2 diabetes inadequately controlled with oral antihyperglycemic drugs were included. Data on the change from baseline to 26 weeks (±10 weeks) of treatment in hemoglobin A1c (HbA1c) and weight, as well as the proportion of patients experiencing hypoglycaemia, were extracted. Fixed-effect pairwise meta-analyses were conducted where data were available from ≥2 studies.. Fifteen RCTs were identified and 11 were meta-analysed. The once-weekly GLP-1 RAs, exenatide long acting release (LAR) and dulaglutide, led to greater, statistically significant mean HbA1c reductions vs basal insulins (exenatide: -0.31% [95% confidence interval -0.42, -0.19], dulaglutide: -0.39% [-0.49, -0.29]) whilst once-daily liraglutide and twice-daily exenatide did not (liraglutide: 0.06% [-0.06, 0.18], exenatide: 0.01% [-0.11, 0.13]). Mean weight reduction was seen with all GLP-1 RAs while mean weight gain was seen with basal insulins. Interpretation of the analysis of hypoglycaemia was limited by inconsistent definitions and reporting. Because of the limited number of available studies sensitivity analyses to explore heterogeneity could not be conducted.. Although weight reduction is seen with all GLP-1 RA's, only the once-weekly agents, exenatide LAR and dulaglutide, demonstrate significant HbA1c reductions when compared to basal insulins.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Exenatide; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptides; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Immunoglobulin Fc Fragments; Incretins; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Liraglutide; Peptides; Recombinant Fusion Proteins; Venoms

Insulin requirements may change during pregnancy, and the optimal treatment for pre-existing diabetes is unclear. There are several insulin regimens (e.g. via syringe, pen) and types of insulin (e.g. fast-acting insulin, human insulin).. To assess the effects of different insulin types and different insulin regimens in pregnant women with pre-existing type 1 or type 2 diabetes.. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 October 2016), ClinicalTrials.gov (17 October 2016), the WHO International Clinical Trials Registry Platform (ICTRP; 17 October 2016), and the reference lists of retrieved studies.. We included randomised controlled trials (RCTs) that compared different insulin types and regimens in pregnant women with pre-existing diabetes.We had planned to include cluster-RCTs, but none were identified. We excluded quasi-randomised controlled trials and cross-over trials. We included studies published in abstract form and contacted the authors for further details when applicable. Conference abstracts were superseded by full publications.. Two review authors independently assessed trials for inclusion, conducted data extraction, assessed risk of bias, and checked for accuracy. We assessed the quality of the evidence using the GRADE approach.. The findings in this review were based on very low-quality evidence, from single, small sample sized trial estimates, with wide confidence intervals (CI), some of which crossed the line of no effect; many of the prespecified outcomes were not reported. Therefore, they should be interpreted with caution. We included five trials that included 554 women and babies (four open-label, multi-centre, two-arm trials; one single centre, four-arm RCT). All five trials were at a high or unclear risk of bias due to lack of blinding, unclear methods of randomisation, and selective reporting of outcomes. Pooling of data from the trials was not possible, as each trial looked at a different comparison.1. One trial (N = 33 women) compared Lispro insulin with regular insulin and provided very low-quality evidence for the outcomes. There were seven episodes of pre-eclampsia in the Lispro group and nine in the regular insulin group, with no clear difference between the two groups (risk ratio (RR) 0.68, 95% CI 0.35 to 1.30). There were five caesarean sections in the Lispro group and nine in the regular insulin group, with no clear difference between the two groups (RR 0.59, 95% CI 0.25 to 1.39). There were no cases of fetal anomaly in the Lispro group and one in the regular insulin group, with no clear difference between the groups (RR 0.35, 95% CI 0.02 to 8.08). Macrosomia, perinatal deaths, episodes of birth trauma including shoulder dystocia, nerve palsy, and fracture, and the composite outcome measure of neonatal morbidity were not reported.2. One trial (N = 42 women) compared human insulin to animal insulin, and provided very low-quality evidence for the outcomes. There were no cases of macrosomia in the human insulin group and two in the animal insulin group, with no clear difference between the groups (RR 0.22, 95% CI 0.01 to 4.30). Perinatal death, pre-eclampsia, caesarean section, fetal anomaly, birth trauma including shoulder dystocia, nerve palsy and fracture and the composite outcome measure of neonatal morbidity were not reported.3. One trial (N = 93 women) compared pre-mixed insulin (70 NPH/30 REG) to self-mixed, split-dose insulin and provided very low-quality evidence to support the outcomes. Two cases of macrosomia were reported in the pre-mixed insulin group and four in the self-mixed insulin group, with no clear difference between the two groups (RR 0.49, 95% CI 0.09 to 2.54). There were seven cases of caesarean section (for cephalo-pelvic disproportion) in. With limited evidence and no meta-analyses, as each trial looked at a different comparison, no firm conclusions could be made about different insulin types and regimens in pregnant women with pre-existing type 1 or 2 diabetes. Further research is warranted to determine who has an increased risk of adverse pregnancy outcome. This would include larger trials, incorporating adequate randomisation and blinding, and key outcomes that include macrosomia, pregnancy loss, pre-eclampsia, caesarean section, fetal anomalies, and birth trauma.

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin Lispro; Pregnancy; Pregnancy Complications; Pregnancy in Diabetics

Insulin is the mainstay of pharmacotherapy in pregnancy complicated by diabetes. This review covers the various insulin regimes and preparations, explaining how to use them, and decide appropriate doses in pregnancy. It approaches insulin treatment from a patient - centred, as well as physician and obstetrician friendly viewpoint, providing pragmatic guidance for management of diabetes in pregnancy.

Topics: Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Pregnancy; Pregnancy in Diabetics

Topics: Diabetes Mellitus, Type 2; Drug Substitution; Female; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male

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

Diabetes during pregnancy causes both fetal and maternal complications. Insulin is the most effective pharmacological treatment for controlling hyperglycemia during gestation and can limit adverse outcomes. Insulin detemir (IDet), a novel basal insulin, has already been used for this indication for several years. It was reclassified in 2012 by the FDA from category C to category B for the treatment of pregnant women with diabetes.. This article reviews published data regarding the use of IDet during pregnancy. We discuss pharmacokinetic and pharmacodynamic qualities of IDet and potential advantages for its use during pregnancy.. IDet is a viable option for the management of diabetes during pregnancy. Though data is limited, its safety and efficacy is probably comparable to human insulin, and in some aspects superior to it. More data, specifically for IDet in pregnancies complicated by gestational diabetes (GDM) or type 2 diabetes, is needed.

Topics: Animals; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Humans; Hypoglycemic Agents; Insulin Detemir; Pregnancy

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

Treat-to-target trial designs compare investigational insulins with a standard insulin. Treat-to-target trials force-titrate insulin dosages to achieve a prespecified treatment goal. With comparable glycaemic control, comparisons of safety endpoints such as hypoglycaemia can be made to establish the risk-benefit profile of the new insulin. Glargine versus NPH showed comparable A1C reductions; however, A1C <7% without associated nocturnal hypoglycaemia was reached in more patients on glargine and overall hypoglycaemia was lower. Detemir versus glargine showed non-inferiority between the groups; however, with less weight gain and more injection site reactions with detemir. Detemir/aspart versus glargine/aspart showed non-inferiority between the treatments, however, with less weight gain in the detemir group but comparable risk of hypoglycaemia. Degludec in combination with aspart versus glargine/aspart showed comparable A1C reductions. However, degludec-treated patients had less overall hypoglycaemia and less nocturnal hypoglycaemia. Because insulin titrations are guided by goal attainment with each treatment, treat-to-target trials enable clinicians to determine differences in non-glycaemic treatment effects, such as rates of hypoglycaemia and weight gain, at the same level of glycaemic control.

Topics: 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 Glargine; Insulin, Long-Acting; Male; Randomized Controlled Trials as Topic; Risk Assessment; Treatment Outcome

Integrating patient-centered diabetes care and algorithmic medicine poses particular challenges when optimized basal insulin fails to maintain glycaemic control in patients with type 2 diabetes. Multiple entwined physiological, psychosocial and systems barriers to insulin adherence are not easily studied and are not adequately considered in most treatment algorithms. Moreover, the limited number of alternatives to add-on prandial insulin therapy has hindered shared decision-making, a central feature of patient-centered care. This article considers how the addition of a glucagon-like peptide 1 (GLP-1) analogue to basal insulin may provide new opportunities at this stage of treatment, especially for patients concerned about weight gain and risk of hypoglycaemia. A flexible framework for patient-clinician discussions is presented to encourage development of decision-support tools applicable to both specialty and primary care practice.

Topics: Blood Glucose; Decision Support Systems, Clinical; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Exenatide; Fasting; Female; Glucagon-Like Peptide 1; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin, Long-Acting; Male; Meals; Patient Preference; Patient-Centered Care; Peptides; Venoms; Weight Gain

To review the available evidence regarding dosing conversion between glargine and detemir in an effort to assist clinicians in performing dosing conversion.. A MEDLINE literature search was performed using the search terms glargine and detemir for articles published through August 2013.. All English-language clinical trials were reviewed for inclusion of dosing and/or pharmacokinetic data.. A total of 7 large (n ≥ 258) randomized controlled trials (RCTs) comparing glargine and detemir in patients with type 1 and 2 diabetes had dosing equivalency data available. In these 7 RCTs, on average, a 38% higher detemir dose was required (range = 8.0%-77.2%) to achieve glucose control comparable to that achieved with glargine. A 24-hour isoglycemic clamp study conducted in 11 patients with type 1 diabetes demonstrated that the duration of action of detemir is dose dependent, with increasing doses of detemir resulting in increased duration of action of detemir. Pharmacokinetic studies conducted in patients with type 2 diabetes are conflicting, although the majority of evidence suggests that glargine provides a longer duration of glycemic control as compared with detemir.. When performing conversion between glargine and detemir, prescribers should be aware that higher doses of detemir as compared with glargine may be necessary to achieve the same glycemic control. Additionally, twice-daily injections of detemir should be considered in clinical situations in which glucose control appears to decline after 12 hours, especially with doses ≤0.4 units/kg/d in patients with type 1 diabetes.

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting

Diabetes mellitus is a common endocrine disorder in feline practice, affecting approximately 1 in 200 cats. The majority of diabetic cats have type 2 diabetes mellitus, which results from a combination of peripheral insulin resistance and a progressive reduction in insulin production.. While usually easy to diagnose, management of diabetes mellitus presents a number of challenges for practitioners and clients alike. Practitioners must decide on diet, insulin type and dose, monitoring method and intensity, and concomitant therapy, which will vary based on individual patient and client needs, and geographic location. Practitioners may also encounter patients with diabetic ketoacidosis or other diabetic complications, and patients with multiple concurrent diseases. Clients may be challenged by the substantial time and financial commitment involved in owning a diabetic cat.. Understanding the pathophysiology, optimal treatment protocols and current goals of diabetes management will benefit practitioners managing diabetic cats. This article reviews the most current management plans for feline diabetics. It places particular emphasis on best practice for achieving diabetic remission, which is an attainable goal in the majority of newly diagnosed diabetic cats.. The information in this article is drawn from the recent human and veterinary literature, including prospective and retrospective studies. The body of prospective clinical data on the use of newer, long-acting insulins (glargine and especially detemir) in cats is limited, but growing.

Topics: Animals; Cat Diseases; Cats; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Drug Administration Schedule; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting

Topics: Administration, Oral; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin, Long-Acting; Patient-Centered Care; Practice Guidelines as Topic

Lowering blood glucose with insulin therapy towards beneficial target levels while also avoiding hypoglycaemia is a challenging task. An important confounding factor, which might be under-appreciated in this scenario, is that of variable glucose readings causing difficulties with dose adjustment. Furthermore, this glucose variability is, to some extent, a reflection of variability in the glucose-lowering action of the insulin therapy itself. Not only is glucose variability a major confounding factor in disease management but it is possibly also of direct prognostic consequence and is increasingly recognized as an informative measurement in diabetes management. The scope for insulin-induced glucose variability is particularly great with basal insulins because of their prolonged absorption from high-dose depots. Pharmacodynamic (PD) variability manifests as both fluctuations in the level of glucose-lowering effect over time, and as inconsistencies in the response from one injection to another. Well-controlled pharmacokinetic (PK)/PD studies using repeated isoglycaemic clamp methodology clearly how that many injected basal insulin products have high variable absorption with correspondingly variable action. Incomplete resuspension and precipitation appear to be important issues with regard to unpredictability in this action, while an inadequate duration of action relative to the dosing interval results in a fluctuating action profile. There are some ultra-long-acting basal insulins with novel protraction mechanisms currently in clinical development for which clamp studies show markedly improved PK/PD profiles.

Topics: Analysis of Variance; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin, Long-Acting; Male; 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

Primary care practitioners are increasingly responsible for the management of the escalating numbers of patients with type 2 diabetes. The majority of these patients will require insulin replacement therapy as their disease progresses, because glycemic control is often unsustainable using oral antidiabetic drugs. This review explains the practicalities of initiating and optimizing basal insulin in clinical practice, emphasizing the need for regular glycated hemoglobin (A1c) monitoring to allow timely initiation of insulin when the A1c target is not met. The importance of patient education in overcoming barriers to insulin is discussed, as well as the choice of available basal insulins and the necessity to optimize basal insulin dosage by self-titration. The traditional view of insulin therapy as a last resort is challenged with the modern basal insulin analogues (insulin detemir and insulin glargine), which offer simple and effective glycemic control with a reduced risk of hypoglycemia compared with older insulin formulations such as neutral protamine Hagedorn.

Topics: Decision Making; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Patient Education as Topic; Primary Health Care

The progressive nature of type 2 diabetes (T2D) requires practitioners to periodically evaluate patients and intensify therapy when glycemic targets become unattainable with their current treatment regimen. Traditional first- and second-line antidiabetic agents such as metformin and the sulfonylureas do not prevent the characteristic decline in beta-cell function associated with T2D; insulin replacement therapy can therefore quickly become a necessity in some patients. Basal insulin initiation provides an excellent platform to which rapid-acting prandial insulin doses can easily be added, potentially in a stepwise manner, as disease progresses. Premix insulin regimens are another effective intensification option following basal insulin initiation, but are most effective in insulin-naïve patients. The use of insulin in combination with modern T2D agents, such as the incretin-based therapies, has the potential to improve glycemic control while limiting insulin-associated weight gain and hypoglycemia. Further clinical data and approval are required before practitioners can fully endorse this novel approach.

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

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

Insulin have been recommended to decrease glycosylated hemoglobin (HbA1c) level in type 2 diabetes mellitus (T2DM) patients whose blood glucose control are unsatisfactory by using oral hypoglycemic drugs.. To systematically estimate the therapeutic effect and security of insulin glargine and insulin detemir for treatment of type 2 diabetes mellitus.. We searched the Cochrane library, PubMed, EMBASE, etc databases. Quality evaluation of all randomized control tests (RCT) enrolled was conducted according to Cochrane manual, and meta-analysis was performed by using RevMan5.0 software.. Both insulin glargine and insulin detemir can effectively control T2DM patient's blood glucose.. Insulin detemir has evident superiority on reducing body weight than insulin glargine. As the doses are concerned, daily insulin dose of insulin detemir is higher than insulin glargine.

Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Insulin Detemir; Insulin Glargine; 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

This review addresses the apparent disconnect between international guideline recommendations, real-life clinical practice and the results of clinical trials, with regard to the initiation of insulin using basal (long-acting) or premixed insulin analogues in patients with type 2 diabetes (T2D). English language guidelines vary considerably with respect to recommended glycaemic targets, the selection of human vs analogue insulin, and choice of insulin regimen. Randomised trials directly comparing insulin initiation between basal and premixed analogues are scarce, and hard endpoint outcome data are inadequate. The evidence presented suggests that a major component of the HbA1c not being attained in every day clinical practice may be a result of factors that are not adequately addressed in forced titration trials of highly motivated patients, including failure to comply with complex treatment and monitoring regimens. Enforced intensification of unrealistic complex treatment regimens and glycaemic targets may theoretically worsen the psychological well-being in some patients. More simple and sustainable treatment regimens and guidelines are urgently needed. As for the use of insulin in T2D, there is limited evidence to convincingly support that initiation of insulin using basal insulin analogues is superior to initiation using premixed insulin analogues. While awaiting improved clinical efficacy and cost-effectiveness data, practical guidance from national and international diabetes organisations should consider more carefully the importance of: i) being clear and consistent; and ii) the early implementation of sustainable and cost-effective insulin treatment regimens with an emphasis on optimising treatment ease of use and patient compliance.

Topics: Clinical Trials as Topic; Diabetes Mellitus, Type 2; Drug Combinations; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Practice Guidelines as Topic

In people with type 2 diabetes mellitus (T2DM), the incretin effect is reduced, but the recent advent of dipeptidyl peptidase-4 inhibitors and glucagon-like peptide (GLP)-1 agonists/analogues has enabled restoration of at least some of the function of the incretin system, with accompanying improvements in glycaemic control. Two GLP-1 receptor agonists/analogues are currently approved for the treatment of T2DM-exenatide (Byetta®, Eli Lilly & Co., Indianapolis, IN, US) and liraglutide (Victoza®, Novo Nordisk, Bagsvaerd, Denmark); a once-weekly formulation of exenatide (Bydureon®, Eli Lilly & Co.) has also been approved by the European Medicines Agency. The National Institute for Health and Clinical Excellence (NICE) has recently published guidance on the use of liraglutide in T2DM, based on evidence from the Liraglutide Effect and Action in Diabetes (LEAD) Phase III trial programme, which compared liraglutide with existing glucose-lowering therapies, such as exenatide and insulin glargine. The LEAD programme reported HbA1c reductions from 0.8 to 1.5% with liraglutide (1.2 and 1.8 mg), accompanied by low rates of hypoglycaemia and some weight loss; side effects were primarily gastrointestinal in nature (e.g. nausea and diarrhoea). Based on the findings of the LEAD studies and the NICE recommendation, liraglutide now represents an important therapy widely available in the UK for certain patient groups, including those with a body mass index (BMI) ≥35.0 kg/m(2) , and patients with a BMI <35 kg/m(2) who are considered unsuitable for insulin and are failing to meet targets for glycaemic control with oral agents. NICE guidelines still suggest that most patients without considerable obesity (BMI <35 kg/m(2) ) are probably best managed using insulin therapy. Evidence also suggests a future role for GLP-1 mimetics in combination with basal insulin.

Topics: Algorithms; Diabetes Mellitus, Type 2; Drug Administration Schedule; Evidence-Based Medicine; Exenatide; Female; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Liraglutide; Male; Peptides; Randomized Controlled Trials as Topic; United Kingdom; Venoms; Weight Loss

Because of the progressive nature of type 2 diabetes, basal insulin alone may not be able to provide sufficient glycemic control over the long term, and thus insulin regimens will typically need to be intensified--especially for controlling postprandial glucose excursions. In patients with type 2 diabetes requiring more intensive intervention, insulin analog premix formulations can offer a simple, effective, and convenient option for tighter management of hyperglycemia in lieu of a traditional basal-bolus regimen.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin Lispro; Insulin, Long-Acting; Male; Metformin; Postprandial Period; Randomized Controlled Trials as Topic

Topics: Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Drug Costs; Drug Monitoring; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Insulin, Short-Acting; United Kingdom

Topics: Administration, Oral; Adult; Aged; Blood Glucose; Comorbidity; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Substitution; Drug Therapy, Combination; Female; Germany; Glycated Hemoglobin; Humans; Hypercholesterolemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin Detemir; Insulin Lispro; Insulin, Long-Acting; Male; Middle Aged; Obesity, Morbid; Young Adult

Insulin detemir (Levemir®) is a long-acting insulin analogue indicated for use as basal insulin therapy in patients with type 1 or 2 diabetes mellitus. The protracted action of insulin detemir is explained by increased self-association and reversible binding to albumin, which slows its systemic absorption from the injection site. In glucose-clamp studies, less within-patient variability in glucose-lowering effect was seen with insulin detemir than with neutral protamine Hagedorn (NPH) insulin or insulin glargine in patients with type 1 or 2 diabetes. The beneficial effect of insulin detemir on glycaemic control was shown in numerous randomized, open-label, multicentre trials, including when used as basal-bolus therapy in patients with type 1 or 2 diabetes and as basal therapy in addition to oral antidiabetic drugs in insulin-naive patients with type 2 diabetes. In terms of glycosylated haemoglobin (HbA(1c)).[primary endpoint in most trials], insulin detemir was generally at least as effective as NPH insulin, insulin glargine or insulin lispro protamine suspension in patients with type 1 or 2 diabetes, and at least as effective as biphasic insulin aspart in patients with type 2 diabetes. Less within-patient variability in blood glucose was also generally seen with insulin detemir than with NPH insulin in patients with type 1 or 2 diabetes. Significantly less weight gain was generally seen with insulin detemir than with NPH insulin in patients with type 1 diabetes or with insulin detemir than with NPH insulin, insulin glargine, insulin lispro protamine suspension or biphasic insulin aspart (in one study) in patients with type 2 diabetes (i.e. insulin detemir generally had a weight-sparing effect). The addition of insulin detemir to liraglutide plus metformin improved glycaemic control in insulin-naive patients with type 2 diabetes and inadequate glycaemic control, although a significantly greater reduction in bodyweight was seen in patients receiving liraglutide plus metformin than in those receiving add-on therapy with insulin detemir. Results of two trials in patients aged 2-16 or 6-17 years (and a subgroup analysis in children aged 2-5 years) indicate that a basal-bolus insulin regimen incorporating insulin detemir appears to be a suitable option for use in paediatric patients with type 1 diabetes. Less within-patient variation in self-measured fasting plasma glucose was seen with insulin detemir than with NPH insulin in one of the studies. Insulin detem

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin, Long-Acting; Randomized Controlled Trials as Topic; Treatment Outcome

We compared the effect of insulin lispro protamine suspension (ILPS) with that of insulin glargine and insulin detemir, all given as basal supplementation, in the treatment of patients with type 2 diabetes.. We conducted an electronic search until February 2012, including online registries of ongoing trials and abstract books. All randomized controlled trials comparing ILPS with insulin glargine or detemir with a duration of ≥12 weeks were included.. We found four trials lasting 24-36 weeks involving 1,336 persons: three studies compared ILPS with glargine, and one trial compared ILPS with detemir. There was no significant difference in change in HbA(1c) level between ILPS and comparators, in the proportion of patients achieving the HbA(1c) goals of ≤6.5 or <7%, in weight change, or in daily insulin doses. There was no difference in overall hypoglycemia, but nocturnal hypoglycemia occurred significantly more with ILPS than with comparator insulins (mean difference 0.099 events/patient/30 days [95% CI 0.03-0.17]). In a prespecified sensitivity analysis comparing data obtained in patients who remained on their once-daily insulin regimen, not significantly different event rates for nocturnal hypoglycemia were observed between ILPS and comparator insulins (0.063 [-0.007 to 0.13]), and ILPS was associated with lower insulin dose (0.07 units/kg/day [0.05-0.09]).. There is no difference between ILPS and insulin glargine or detemir for targeting hyperglycemia, but nocturnal hypoglycemia occurred more frequently with ILPS than with comparator insulins. Nocturnal hypoglycemia was not significantly different in people who injected insulin once daily.

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

Two basal insulin analogues, insulin glargine once daily and insulin detemir once or twice daily, are marketed in Canada.. To estimate the long-term costs of insulin glargine once daily (QD) versus insulin detemir once or twice daily (QD or BID) for type 1 (T1DM) and type 2 (T2DM) diabetes mellitus from a Canadian provincial government's perspective.. A cost-minimization analysis comparing insulin glargine (IGlarg) to insulin detemir (IDet) was conducted using a validated computer simulation model, the CORE Diabetes Model. Lifetime direct medical costs including costs of insulin treatment and diabetes complications were projected. T1DM and T2DM patients' daily insulin dose (T1DM: IGlarg QD 26.2 IU; IDet BID 33.6 IU; T2DM: IGlarg QD 47.2 IU; IDet QD 65.7 IU or IDet BID 80.4 IU) was derived from a meta-analysis of randomized trials. All patients were assumed to stay on the same treatment for life. Costs were discounted at 5% per annum and reported in 2010 Canadian Dollars.. The meta-analysis showed T1DM and T2DM patients had similar HbA(1c) change from baseline when receiving IGlarg compared to IDet (T1DM: 0.002%-points; p = 0.97; T2DM: -0.05%-points; p = 0.28). Treatment of T1DM patients with IGlarg versus IDet BID resulted in lifetime cost savings of $4231 per patient. Treatment of T2DM patients with IGlarg resulted in lifetime cost savings of $4659 per patient versus IDet QD and cost savings of $8709 per patient versus IDet BID.. Similar HbA(1c) change from baseline can be achieved with a lower IGlarg than IDet dose. From the perspective of a Canadian provincial government, treatment of T1DM and T2DM patients with IGlarg instead of IDet can generate long-term cost savings. Main limitations include trial data were derived from multi-country studies rather than the Canadian population and self-monitoring blood glucose costs were not included.

Topics: Cost-Benefit Analysis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Health Care Costs; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Markov Chains; Models, Economic; Risk

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

Chronically elevated blood glucose levels are associated with significant morbidity and mortality. Many diabetes patients will eventually require insulin treatment to maintain good glycaemic control. There are still uncertainties about the optimal insulin treatment regimens for type 2 diabetes, but the long-acting insulin analogues seem beneficial. Several reviews have compared either insulin detemir or insulin glargine to NPH insulin, but research directly comparing both insulin analogues is limited.. To assess the effects of insulin detemir and insulin glargine compared with each other in the treatment of type 2 diabetes mellitus.. We searched MEDLINE, EMBASE, The Cochrane Library, online registries of ongoing trials and abstract books. Date of last search was January 2011.. All randomised controlled trials comparing insulin detemir with insulin glargine with a duration of 12 weeks or longer were included.. Two authors independently selected the studies and extracted the data. Pooling of studies by means of random-effects meta-analysis was performed.. This review examined four trials lasting 24 to 52 weeks involving 2250 people randomised to either insulin detemir or glargine. Overall, risk of bias of the evaluated studies was high. Insulin glargine was dosed once-daily in the evening. Insulin detemir was initiated once-daily in the evening with the option of an additional dose in the morning in three studies and initiated twice-daily in one study. Of randomised patients 13.6% to 57.2% were injecting insulin detemir twice-daily at the end of trial.Glycaemic control, measured by glycosylated haemoglobin A1c (HbA1c) and HbA1c equal to or less than 7% with or without hypoglycaemia, did not differ statistically significantly between treatment groups.The results showed no significant differences in overall, nocturnal and severe hypoglycaemia between treatment groups.Insulin detemir was associated with less weight gain. Treatment with insulin glargine resulted in a lower daily basal insulin dose and a lower number of injection site reactions.There was no significant difference in the variability of FPG or glucose values in 24-hour profiles between treatment groups. It was not possible to draw conclusions on quality of life, costs or mortality. Only one trial reported results on health-related quality of life and showed no significant differences between treatment groups.. Our analyses suggest that there is no clinically relevant difference in efficacy or safety between insulin detemir and insulin glargine for targeting hyperglycaemia. However, to achieve the same glycaemic control insulin detemir was often injected twice-daily in a higher dose but with less weight gain, while insulin glargine was injected once-daily, with somewhat fewer injection site reactions.

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

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 prevalence of diabetes and cost of associated treatment are steadily increasing, as is the resulting burden on healthcare systems worldwide. Current treatment recommendations for Type 1 and Type 2 diabetes advise a prominent role for basal insulin. We examined the published health-economic literature pertaining to the basal insulin analog insulin detemir (IDet) to determine whether IDet is a cost-saving and/or cost-effective treatment for suboptimally controlled Type 1 or Type 2 diabetes. A total of 15 modeling studies were assessed, most of which found IDet to be cost effective compared with neutral protamine Hagedorn and as cost effective as insulin glargine. Those that did not find IDet to be cost effective set the disutility of hypoglycemic events to almost zero or assumed a higher dose of IDet with no difference in treatment effect, ignoring the clinical benefits and cost savings associated with IDet in studies demonstrating comparable or superior glycemic control with less hypoglycemia versus other basal insulins. The evidence suggests that IDet is cost effective versus neutral protamine Hagedorn and at least as cost effective as insulin glargine in the treatment of patients with suboptimally controlled Type 1 and Type 2 diabetes.

Topics: Blood Glucose; Cost Savings; Cost-Benefit Analysis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Costs; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin, Long-Acting; Models, Economic; Quality-Adjusted Life Years; Time Factors; Treatment Outcome

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

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

Basal insulin analogs are used to minimize unpredictable processes of NPH insulin. Modification of the human insulin molecule results in a slower distribution to peripheral target tissues, a longer duration of action with stable concentrations and thus a lower rate of hypoglycemia. Insulin detemir is a basal insulin analog that provides effective therapeutic options for patients with type 1 and type 2 diabetes. For glycemic control, no significant differences were found in HbA1c levels compared with NPH and insulin glargine. It is comparable with insulin glargine in significantly reducing rates of all types of hypoglycemia. Clinical studies have demonstrated that detemir is responsible for significantly lower within-subject variability and no or less weight gain than NPH insulin and glargine. Recent pharmacodynamic studies have shown that detemir can be used once daily in many patients with diabetes. Together with patient-friendly injection devices and dose adjustments, it provides a treatment option with the potential to lower the key barriers of adherence to insulin therapy in type 2 diabetes. Recent guidelines for treatment of type 2 diabetes suggest starting intensive therapy of hyperglycemia at an early stage of diabetes and recommend therapeutic options that provide the possibility of reaching HbA1c goals individually, with a low risk of hypoglycemia or other adverse effects of treatment. The properties of insulin detemir match these requirements.

Topics: Body Weight; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections; Insulin; Insulin Detemir; Insulin, Long-Acting; Male; Medication Adherence; Pregnancy; Treatment Outcome

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

A pooled analysis of randomized controlled trials of individuals with type 2 diabetes mellitus (T2DM) was conducted to compare dosing and impact of two basal insulin analogs, insulin glargine (glargine) and insulin detemir (detemir), on weight and hemoglobin A1c (A1c).. Twenty-two studies of at least 20 weeks in duration in individuals with T2DM initiating glargine/detemir were included. Results were combined using a weighted-average method and a bivariate random effect model. Outcomes included changes in weight, A1c, and insulin dose from study start to end.. One study was head-to-head comparison of glargine and detemir. Detemir (four studies) was administered once or twice daily, with 50% starting on detemir once daily but needing therapy intensification. Glargine was used once daily in all 22 studies. The Egger test was borderline significant for change in weight over the course of the treatment for glargine (0.29; 90% confidence interval [CI] -0.01, 0.58), and heterogeneity was not observed for detemir (-0.18; 90% CI -0.59, 0.23). Heterogeneity was observed for change in A1c over the course of the treatment (glargine, -1.19, 90% CI -1.74, -0.63; detemir, -2.65, 90% CI -4.86, -0.45). Nonheterogeneity for change in A1c over the course of the treatment was achieved by excluding five studies for glargine and one study for detemir; however, all studies were included in subsequent analyses. In the unadjusted model, glargine and detemir showed similar results for mean A1c change (-1.4% vs. -1.4%), weight gain (2.5 vs. 1.7 kg), and weight/A1c (1.8 vs. 1.2 kg/%). A significantly higher detemir dose was needed to achieve the same A1c change (51.5 vs. 38.8 U/day).. Although absolute weight gain was higher with glargine versus detemir, weight gain per A1c change was similar. A higher detemir dose was required to achieve a similar A1c reduction.

Topics: Body Weight; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Randomized Controlled Trials as Topic

Among the growing population of individuals with type 2 diabetes mellitus, many patients are failing to meet glycemic targets and are therefore at increased risk of complications.. Rapid-acting insulin analogs (ie, aspart, lispro, glulisine) have a pharmacokinetic profile that mirrors endogenous insulin more closely than regular human insulin. These insulin analogs can also be given closer to mealtimes and are less likely to cause hypoglycemia. Long-acting insulin analogs (ie, detemir, glargine) have relatively flat time-action profiles and last up to 24 hours, thus simulating endogenous basal insulin more precisely than neutral protamine Hagedorn insulin and producing less nocturnal hypoglycemia. The simplicity and efficacy of insulin analogs should help facilitate a patient's transition to insulin therapy. Current guidelines advocate starting insulin therapy in patients who have not achieved glycemic targets or those with glycated hemoglobin greater than 8.5% and adjusting doses as necessary. Two case studies illustrate the benefits of insulin analog therapy.. Insulin analogs offer many benefits over human insulins, including improved physiologic profile, greater convenience, reduced risk of hypoglycemia, and, in some instances, less weight gain. Combined, these elements may increase a patient's adherence to treatment, potentially increasing the level of glycemic control and improving the prognosis in patients with type 2 diabetes mellitus.

Topics: Algorithms; Amyloid; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Exenatide; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin Secretion; Insulin, Long-Acting; Islet Amyloid Polypeptide; Life Style; Male; Middle Aged; Pancreas; Patient Compliance; Peptides; Venoms

The recent evidence-based shift towards an algorithm of early initiation and aggressive titration of insulin therapy in the management of type 2 diabetes requires the use of an effective insulin formulation that is both safe and acceptable to patients and physicians alike. The advent of the long-acting insulin analogues, insulin detemir and glargine, in the last decade has revolutionized insulin therapy in type 2 diabetes. Their unique pharmacokinetic and pharmacodynamic properties have offered tangible advantage over the conventional intermediate and long-acting insulin preparations in terms of improving glucose control as well as reducing risk of hypoglycemia and weight gain. This review focuses on the pharmacodynamic properties of the long-acting insulin analogue detemir, the outcome of studies on its relative efficacy and safety as well as its proposed place in the management of type 2 diabetes.

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

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

The efficacy and tolerability of insulin detemir (detemir), a long-acting basal insulin analog, is already well documented for type 1 diabetes. This article reviews new evidence, in particular on the weight-sparing effect of detemir and its use in type 2 diabetes.. All clinical trials of detemir published since a 2006 drug evaluation and up to December 2007, including large real-life studies, are covered in this review. Earlier studies are cited when relevant.. In type 2 diabetes, detemir used once or twice daily achieves equivalent glycemic control to other basal insulins in treat-to-target trials but tends to improve control in patients switched from other basal insulins in basal-oral regimens. The risk of hypoglycemia (nocturnal, overall, or both) is substantially and significantly reduced with detemir compared with NPH insulin. Body weight increase is consistently significantly lower with detemir than with NPH in type 1 and type 2 diabetes. The results of both glucose clamp studies and clinical trials support initiation of detemir at a once-daily dosing regimen.

Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Evaluation; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Detemir; Insulin, Long-Acting

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

Intensive insulin therapy aimed at achieving normoglycaemia is becoming increasingly accepted in the treatment of type 2 diabetes (T2DM) to reduce the risk of diabetes-related complications. Insulin therapy is increasingly combined with oral antidiabetic drugs (OADs) to moderate insulin dosage, reduce weight gain and confer cardiovascular protection. However, traditional insulins are associated with limitations that may act as barriers to initiation, and intensive use of insulin therapy. The advent of newer, longer-acting, basal insulin analogues, such as insulin glargine (glargine) and insulin detemir (detemir), offer improved pharmacokinetic and pharmacodynamic profiles compared with neutral protamine Hagedorn insulin (NPH). This potentially provides concomitant improvements in safety, efficacy and variability of glycaemic control. This paper reviews the properties of these new long-acting, basal insulin analogues and their potential roles in facilitating the initiation and optimisation of insulin therapy. Studies that reported the use of insulin and insulin analogues for the treatment of T2DM were identified using Medline. Key search terms included: 'insulin glargine', 'insulin detemir', 'NPH insulin', 'basal insulin', 'long-acting insulin', 'insulin analogue', 'pharmacokinetics', 'pharmacodynamics', 'dose titration', 'algorithms' and 'type 2 diabetes'. Abstracts presented at the American Diabetes Association and the European Association for the Study of Diabetes annual congresses were also searched. The data show that the long-acting insulin analogues glargine and detemir both offer a low risk of hypoglycaemia and improved glycaemic control. Aggressive dose titration with glargine and detemir facilitates attainment of glycaemic control targets. The goal of achieving good glycaemic control with a low risk of hypoglycaemia may be more feasible with newer insulin therapies as part of a simple basal insulin regimen with continued OADs.

Topics: Administration, Oral; Amino Acid Sequence; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Molecular Sequence Data; Recombinant Proteins

Topics: Animals; Biological Availability; Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Injections, Subcutaneous; Insulin; Insulin Detemir; Insulin, Long-Acting; Protein Binding; Receptor, IGF Type 1; Receptor, Insulin; Solubility

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

Insulin is one of the fundamental tools for the management of diabetes mellitus. All type 1 diabetic patients and most of the type 2 require the appropriate support of insulin for good glycemic control, long term healthy outcome and also to overcome the acute crisis. It is almost impossible to mimic the endogenous physiological insulin secretion curve by external administration of short acting human insulin and conventional intermediate acting insulin, neutral protamin Hagedorn (NPH), the so called basal insulin. Short acting human insulin has got a delayed onset of action, late peak and a long tail leading to postprandial hyperglycemia and late hypoglycemia. The so called basal insulin (NPH) is not truly a basal or peakless insulin. Its onset of action takes about 2 - 4 hours with a peak action and a tail. It can not maintain a constant basal level leading to premeal and fasting hyperglycemia and chance of hypoglycemia during peak action, particularly after night injection. To overcome the limitations of human insulin, during the last decade, three ultrashort acting and two long acting basal analogues have been developed by modifications of primary molecule of human insulin. The ultrashort acting analogue insulins are insulin lispro, insulin aspart and insulin glulisine. The basal analogues are insulin glargin and insulin detemir. The pharmacokinetic profiles of novel analogue molecules provide a better opportunity to mimic a physiological pattern of insulin administration, better glycemic control, less chance of hypoglycemia, greater flexibility and a healthy longterm outcome.

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting

Weight gain is often perceived as inevitable with insulin therapy, particularly as we strive for tight glycaemic control and are using increasingly proactive insulin titration regimes. The United Kingdom Prospective Diabetes Study documented that weight gain occurs most rapidly soon after insulin therapy is first initiated. The timing of this side effect is particularly undesirable, as weight gain may interfere with patients' adjustment to insulin therapy and may undermine appropriate diabetes self-management behaviours. Until recently, many patients had little alternative other than to accept unwanted weight gain if they were to achieve sufficient glycaemic control to reduce risk of chronic complications of diabetes. Insulin detemir is a novel basal insulin analogue that has consistently been shown in randomized, controlled trials to have a weight-sparing effect (i.e. weight loss or reduced weight gain compared with other insulins) in both type 1 and type 2 diabetes. Indeed, unlike neutral protamine Hagedorn (NPH) insulin, the weight-sparing effect of insulin detemir appears to be most prominent in people who are the most obese. The mechanisms behind the weight-sparing effect of insulin detemir are still being clarified. Reduced risk of hypoglycaemia with insulin detemir, coupled with a more consistent and reliable delivery of the desired dose than is available with traditional basal insulin, such as NPH, has been proposed to minimize defensive snacking by patients, and help to limit weight gain. However, even if this was proven, it would be unlikely to fully explain the weight-sparing effect of insulin detemir. Two additional theories have been put forward. One suggests that due to its novel method of prolonging action via acylation and albumin binding, insulin detemir may differentially influence hepatocytes more than peripheral tissues, thus effectively suppressing hepatic glucose output without promoting lipogenesis in the periphery. The second theory suggests that insulin detemir may be more effective than human insulin in communicating satiety signals within the central nervous system. Further clarification of these hypotheses is required.

Topics: Blood Glucose; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Weight Gain

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 basal insulin analogues glargine and detemir have been subject to a series of trials comparing their clinical profiles to the conventional preparation, neutral protamine Hagedorn (NPH). Careful review of these trials provides opportunities to learn clinically useful lessons about these insulins.. MedLine-indexed trials comparing glargine or detemir to NPH were scrutinized for control, tolerability and dose data. Separate considerations were made for types 1 and 2 diabetes, and for basal-bolus and basal plus oral glucose-lowering drugs (OGLD) therapy. Attention was paid to dosing schedules and 24-h glycaemic profiles.. Collectively, the trials demonstrated an improved balance between glycaemic control and tolerability for both analogues compared to NPH, regardless of regimen and diabetes type. Neither once-daily glargine nor detemir reliably provides 24-h basal insulin replacement in all patients with type 1 diabetes; a waning of effect frequently obliges twice-daily administration. When added to OGLDs in type 2 diabetes, goal-titrated once-daily basal insulin generally lowered HbA(1c) by approximately 1.5%, whereas twice-daily administration tended to increase insulin dose disproportionately to improvement in control. Hence, adding bolus insulin may be a preferable intensification method to dividing the basal dose. Varying injection time or dividing the basal insulin dose predictably affects the pattern of hypoglycaemia and bolus dose requirements. Morning administration tends to require higher dosing than evening administration.. Scrutiny of trials involving glargine and detemir has increased our understanding of how best to dose basal insulins. An individualized approach is still necessary however, and several questions remain that require further research.

Topics: Controlled Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting

With the introduction of insulin detemir (Levemir [Novo Nordisk A/S, Bagsvaerd, Denmark]), a long-acting basal insulin analog, it is an opportune moment to reevaluate the use of basal insulin therapy and consider current treatment strategies, including the use of insulin detemir. This review examines the need for effective treatment options for diabetes and the economic burden of this disease. The importance of achieving glycemic control targets and the role of basal insulin therapy are discussed. Finally, the use of insulin detemir is briefly reviewed with a look at its clinical pharmacology, its use in basal insulin therapy, and its cost-effectiveness.

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

Insulin detemir (Levemir [Novo Nordisk A/S, Bagsvaerd, Denmark]) is a soluble, long-acting basal insulin analog. It differs from human insulin in that the amino acid threonine in position B30 has been removed and a 14-carbon fatty acid (myristic acid) has been acylated to lysine at B29. This modification increases self-association and enables albumin binding of insulin detemir. In this manuscript, the unique molecular properties and the resulting pharmacodynamics of insulin detemir are reviewed. The protracted duration of action, smooth activity profile, and low intrapatient variability of insulin detemir are presented as properties that may potentially help patients maximize glycemic control and minimize the long-term complications of diabetes.

Topics: Amino Acid Sequence; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Molecular Sequence Data

In the treatment of patients with diabetes, the tear of hypoglycemia is a major barrier to initiating, maintaining, and/or intensifying insulin therapy. Insulin detemir (Levemir [Novo Nordisk A/S, Bagsvaerd, Denmark]) is a novel, long-acting, basal insulin analog associated with a reduced risk of hypoglycemia that is available to improve glycemic control. This article discusses clinical trial data on the safety and efficacy of insulin detemir in patients with type 1 and type 2 diabetes. In additions, results from the German cohort of the Predictable Results and Experience in Diabetes through Intensification and Control to Target: An International Variability Evaluation (PREDICTIVE study, a large, multinational observational study examining the clinical effectiveness and safety of insulin detemir, are reviewed. Finally, an evaluation of these data serves to show how the highly predictable action of insulin detemir translates into effective glycemic control with a lower incidence of hypoglycemia.

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

Weight gain can be a significant barrier to the treatment of diabetes. Insulin detemir is a basal insulin analog that can help patients move safely toward glycemic targets with less weight gain. This review discusses the potential adverse effects of, and hypothesis for, weight gain resulting from intensive insulin management of diabetes. In addition, an assessment of all weight change data from clinical trials and observational studies involving insulin detemir are presented. Finally, we discuss how the ability of insulin detemir to closely mimic endogenous insulin secretion leads to more predictable glycemic control with reduced weight gain and provides patients with a more acceptable method of achieving glycemic control.

Topics: Body Weight; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting

Forty-three case reports of patients with type 2 diabetes who were treated with insulin detemir (Levemir, Novo Nordisk A/S, Bagsvaerd, Denmark) were collected from doctors' offices for the purpose of analyzing 4 parameters: (1) effectiveness of glycemic control (fasting blood glucose [FBG] readings and glycosylated hemoglobin [A1C]); (2) tolerability (hypoglycemic episodes and weight gain); (3) dosing regimen; and (4) treatment discontinuations. Patients in the Levemir Early Clinical Experience Case Series showed improvement of mean FBG readings, with a mean decrease of 63 mg/dL from baseline by the third follow-up visit (24-41) weeks from treatment initiation). Mean A1C values decreased during this time from a baseline average of 8.6% to a final average of 7.0%. Four patients on insulin detemir reported hypoglycemic episodes, none of which required special interventions or discontinuation of treatment. A mean weight loss of 5 lb was observed at the final follow-up visit. Twenty-four (55.8%) patients were insulin-naive, and 19 (44.2%) were already on insulin at the time they were started on insulin detemir. Almost 91% of patients were on a once-daily regimen of insulin detemir; 4 patients discontinued treatment during the observation period. Overall, the observations from the Levemir Early Clinical Experience Case Series are good indicators of the early experience with insulin detemir in the United States, and are consistent with findings from controlled trials and large observational studies.

Topics: Aged; Aged, 80 and over; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged; United States

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

Insulin detemir is a novel long-acting insulin analogue with a unique mechanism underlying its prolonged duration of action. Unlike neutral protamine Hagedorn (NPH) insulin (insulin suspension isophane) and insulin glargine, which precipitate after administration, insulin detemir remains soluble after it is injected. The prolonged duration of action of insulin detemir is a result of the ability to self-associate into hexamers and dihexamers, and to bind reversibly to albumin. This mechanism of protraction provides a more prolonged, consistent and predictable glycaemic effect in patients with type 1 or type 2 diabetes mellitus compared with NPH insulin. Clinical studies have demonstrated that insulin detemir administered once or twice daily is at least as effective as NPH insulin and insulin glargine in achieving glycaemic control. Most trials have also shown that insulin detemir exhibits less intrapatient variability in glycaemic control compared with NPH insulin and insulin glargine. One of the benefits of insulin detemir is its favourable effect on bodyweight. Insulin detemir has shown weight neutrality in patients with type 1 diabetes and is associated with less weight gain than NPH insulin in clinical studies. Patients with type 2 diabetes using insulin detemir gain less weight than patients using NPH insulin and insulin glargine. In addition, a reduced risk of hypoglycaemia, particularly nocturnal hypoglycaemia, has been reported with insulin detemir compared with NPH insulin in patients with type 1 and type 2 diabetes. A reduced risk of major and nocturnal hypoglycaemia compared with insulin glargine in patients with type 1 diabetes has also been observed. Together, these data indicate that insulin detemir is a valuable new option for basal insulin therapy in patients with type 1 or type 2 diabetes.

Topics: Clinical Trials as Topic; Cost-Benefit Analysis; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Humans; Insulin; Insulin Detemir; Insulin, Long-Acting

Insulin is an effective treatment for type 2 diabetes (T2D), a progressive condition in which insulin deficiency is one of the core defects. When patients with T2D are unable to achieve glycemic goals with diet and oral antihyperglycemic medications, a common starting insulin regimen consists of basal or premixed insulin added to oral antihyperglycemic medications. When glycemic goals are not achieved with the initial insulin regimen, a basal-bolus regimen is necessary.. This article reviews clinical-trial data on the efficacy and safety profile of prandial premixed insulin analogues (insulin aspart and insulin lispro) compared with basal insulin analogues (insulin glargine, insulin detemir, and insulin lispro protamine suspension), with or without a prandial insulin analogue, in the management of T2D.. A systematic search of Ovid, MEDLINE, and EMBASE (1995-2007) was performed to identify published randomized controlled trials comparing prandial premixed insulin analogues with basal insulin analogues, with or without prandial insulin, in patients with T2D. The search terms were premixed insulin analogues, premixed insulin, biphasic insulin aspart, insulin aspart 70/30, insulin aspart 50/50, premixed insulin lispro, insulin lispro 75/25, insulin lispro 50/50, glargine, and detemir. Abstracts presented at the 2005 and 2006 meetings of the American Diabetes Association and the European Association for the Study of Diabetes and bibliographies of the identified studies were also reviewed. Predetermined criteria for study inclusion were treatment duration of at least 12 weeks, T2D diagnosed using valid criteria, use of a basal insulin analogue (with or without rapid-acting insulin) as a study comparator, and use of well-accepted end points (eg, glycosylated hemoglobin [HbA(1c)], hypoglycemia, preprandial and postprandial blood glucose).. Of the identified randomized controlled trials, 3 studies compared premixed insulin analogues containing 70% or 75% basal and 30% or 25% rapid-acting insulin analogue with basal insulin analogues only, and 3 studies evaluated premixed insulin analogues containing 50% basal and 50% rapid-acting insulin analogue with basal insulin analogues only. Use of prandial premixed insulin analogues was associated with better overall and postprandial glycemic control. In the studies that compared twice-daily premixed insulin analogues with a basal insulin analogue, changes in HbA(1c) ranged from -1.00% to -2.79% and from -0.42% to -2.36%, respectively (P < 0.01). In the studies that compared thrice-daily premixed insulin analogues with a basal insulin analogue, changes in HbA(1c) ranged from -0.72% to -1.2% and from -0.3% to -0.75%, respectively (P < 0.01). These results were achieved with some increase in overall hypoglycemia, but not in nocturnal or severe hypoglycemia. Doses of the premixed insulin analogues were adjusted during the titration period to achieve glycemic goals.. The results of this systematic review suggest that regimens consisting of prandial premixed insulin analogues, which provide both basal and prandial insulin coverage, may be used as an initial insulin regimen in patients with T2D to enable better overall, preprandial, and postprandial glycemic control compared with a basal insulin analogue regimen alone. Premixed insulin analogues are an effective option for initiating and intensifying insulin therapy in patients with T2D.

Topics: Body Weight; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Evidence-Based Medicine; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Randomized Controlled Trials as Topic

Insulin is an effective treatment for type 2 diabetes (T2D), a progressive condition in which insulin deficiency is one of the core defects. When patients with T2D are unable to achieve glycemic goals with diet and oral antihyperglycemic medications, a common starting insulin regimen consists of basal or premixed insulin added to oral antihyperglycemic medications. When glycemic goals are not achieved with the initial insulin regimen, a basal-bolus regimen is necessary.. This article reviews clinical-trial data on the efficacy and safety profile of prandial premixed insulin analogues (insulin aspart and insulin lispro) compared with basal insulin analogues (insulin glargine, insulin detemir, and insulin lispro protamine suspension), with or without a prandial insulin analogue, in the management of T2D.. A systematic search of Ovid, MEDLINE, and EMBASE (1995-2007) was performed to identify published randomized controlled trials comparing prandial premixed insulin analogues with basal insulin analogues, with or without prandial insulin, in patients with T2D. The search terms were premixed insulin analogues, premixed insulin, biphasic insulin aspart, insulin aspart 70/30, insulin aspart 50/50, premixed insulin lispro, insulin lispro 75/25, insulin lispro 50/50, glargine, and detemir. Abstracts presented at the 2005 and 2006 meetings of the American Diabetes Association and the European Association for the Study of Diabetes and bibliographies of the identified studies were also reviewed. Predetermined criteria for study inclusion were treatment duration of at least 12 weeks, T2D diagnosed using valid criteria, use of a basal insulin analogue (with or without rapid-acting insulin) as a study comparator, and use of well-accepted end points (eg, glycosylated hemoglobin [HbA1c], hypoglycemia, preprandial and postprandial blood glucose).. Of the identified randomized controlled trials, 3 studies compared premixed insulin analogues containing 70% or 75% basal and 30% or 25% rapid-acting insulin analogue with basal insulin analogues only, and 3 studies evaluated premixed insulin analogues containing 50% basal and 50% rapid-acting insulin analogue with basal insulin analogues only. Use of prandial premixed insulin analogues was associated with better overall and postprandial glycemic control. In the studies that compared twice-daily premixed insulin analogues with a basal insulin analogue, changes in HbA1c ranged from -1.00% to -2.79% and from -0.42% to -2.36%, respectively (P < 0.01). In the studies that compared thrice-daily premixed insulin analogues with a basal insulin analogue, changes in HbA1c ranged from -0.72% to -1.2% and from -0.3% to -0.75%, respectively (P < 0.01). These results were achieved with some increase in overall hypoglycemia, but not in nocturnal or severe hypoglycemia. Doses of the premixed insulin analogues were adjusted during the titration period to achieve glycemic goals.. The results of this systematic review suggest that regimens consisting of prandial premixed insulin analogues, which provide both basal and prandial insulin coverage, may be used as an initial insulin regimen in patients with T2D to enable better overall, preprandial, and postprandial glycemic control compared with a basal insulin analogue regimen alone. Premixed insulin analogues are an effective option for initiating and intensifying insulin therapy in patients with T2D.

Topics: Diabetes Mellitus, Type 2; Evidence-Based Medicine; Humans; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Randomized Controlled Trials as Topic

A systematic review was undertaken to analyse pharmaco-economic issues in diabetes, with evidence selected on the basis of relevance and immediacy. Pharmaco-economics in diabetes primarily relates to making choices about antidiabetic pharmaceuticals, and this is being influenced by global trends. Trends include increasing numbers of patients with diabetes, with increasing costs of caring for people with diabetes, and an ever-present focus on the costs of pharmaceuticals which are predicted to increase as the pace of development of new medications parallels the increasing incidence of the condition. These developments have influenced the demand for health care in diabetes in the last decade, and will continue to determine this in the coming decade. Recent national experiences are cited to illustrate current issues and to focus specifically upon the challenges facing a raft of new diabetes treatment options now hitting the marketplace, although supported by fewer completed long-term trials. It can be anticipated that these newer agents will be appraised for their cost-effectiveness or value for money. Economic analyses for some of the new technologies are summarized; in general, the peer-reviewed publications using well-accepted and validated models have reported that these technologies are cost-effective. Endorsement of any technology in a national setting is not awarded simply because the incremental cost-effectiveness ratio (ICER) falls below the threshold regarded as value for money. In most national observations the reviewers expressed concerns about assumptions used in economic modelling which resulted in the ICERs being deemed optimistic at best, generally highly uncertain, and resulting in the cost-effectiveness appearing better than it really would be in clinical practice. This has often led to the authorities concluding that the price advantage of new technologies over comparators could not be justified, essentially leading to restrictions in use compared to their licence. In general, a paucity of robust evidence on longer-term outcome data together with a lack of health-related quality of life (HRQOL) data collected in a reliable manner in appropriate patients and amenable to utility (and hence quality adjusted life year or QALY) estimation have resulted in problems for these new drugs at the so-called fourth (cost-effectiveness) hurdle. In the light of these findings, the implications for generating credible fit-for-purpose cost-effectiveness an

Topics: Cost-Benefit Analysis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Economics, Pharmaceutical; Exenatide; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Peptides; Prediabetic State; Venoms

The initiation of insulin therapy is a significant event for patients with diabetes and the physicians who care for them. Reluctance to begin insulin is multifactorial, with major stumbling blocks being the perceived complexity of insulin and fear of hypoglycemia. Recent guidelines supporting earlier introduction of insulin to achieve glycemic goals in patients with type 2 diabetes mellitus will require that traditional approaches to insulin therapy be altered and a new paradigm be introduced into clinical practice. In particular, an understanding of the role of basal insulin in the regulation of glucose and the development of strategies to implement basal insulin therapy can provide a transition that is rational and highly effective in most patients. The strategy also offers a unique approach to diabetes education that permits a focused and patient-specific correction to glucose abnormalities.

Topics: Administration, Oral; Combined Modality Therapy; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting

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

Insulin detemir (Levemir, Novo Nordisk) is a novel, biologically engineered analogue of human insulin that has been successfully developed for clinical use in diabetes as a basal insulin. Its unique mechanism of prolongation of action, achieved through acylation to give reversible albumin binding and additional self-association, goes some way to addressing one of the fundamental limitations of previously available, subcutaneously administered basal insulins, a high level of within-person variability in time-action profile from one injection to another. The pharmacological profile of insulin detemir, characterised in a series of studies, suggested it had the potential to offer efficacy and tolerability advantages in the clinical setting. Such advantages, in comparison to NPH (neutral protamine Hagedorn) insulin, have subsequently been illustrated in trials. Despite glucose control targets that are identical to comparators, insulin detemir achieved levels of glycaemic control that, overall, were at least as good as NPH insulin in the Phase III development programme, with lower variability being a consistent finding. This was associated with consistent risk reductions in nocturnal hypoglycaemic events, which are closely linked with the basal component of insulin therapy. Another consistent finding has been a significantly reduced propensity for weight gain. An all-analogue regimen combining insulin detemir with the rapid-acting insulin aspart illustrated the potential benefits achievable when insulins that are designed to achieve defined pharmacokinetic profiles are employed clinically; blood glucose control, including hypoglycaemia, was significantly superior to a human insulin-based mealtime plus basal regimen. Insulin detemir is, therefore, a valuable addition to the range of exogenous insulins, as it should enable treatment regimens to be constructed that offer good outcomes of efficacy and tolerability.

Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Design; Drug Evaluation, Preclinical; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Randomized Controlled Trials as Topic; Receptor, Insulin

Achieving and maintaining glycemic control (glycated hemoglobin--HbA(1c)< or =7.0% according to American Diabetes Association and < or =6.5% according to International Diabetes Federation) is the primary goal in treating diabetes, which lowers the risk for diabetes-related complications. Insulin therapy is essential for type 1 diabetes treatment. Insulin therapy in type 2 diabetes is initiated when glycemic control is inadequate despite the combination of antihyperglycemic drugs. The type of insulin therapy is selected according to the patient's lifestyle and needs. Multiple insulin injection therapy and premixed insulin therapy are usually administered. In multiple insulin injection therapy, basal insulin is administered one or two times a day, and regular human insulin or rapid-acting insulin analog is administered with each meal. The duration of action of regular insulin is 6-8 hours; therefore, the risk for postprandial hypoglycemia is increased. The action of novel insulin analogs (rapid- and long-acting) closely mimics physiological insulin secretion. Three rapid-acting insulin analogs are currently available: insulin lispro, insulin aspart, and insulin glulisine. Insulin glulisine is the most recently approved rapid-acting insulin analog. It is safe, flexible, and effective in achieving target postprandial glycemic control. Moreover, the pharmacokinetics of insulin glulisine does not depend on the amount of subcutaneous fat. Basal insulins include intermediate-acting human insulins (neutral protamine Hagedorn) and long-acting insulin analogs (insulin glargine, insulin detemir). The latter are the optimal choice covering basal insulin requirement. Compared to neutral protamine Hagedorn insulin, long-acting insulin analogs have no pronounced concentration peak and reduce nocturnal hypoglycemia risk and weight gain.

Topics: Adolescent; Adult; Age Factors; Aged; Algorithms; Blood Glucose; Child; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Detemir; Insulin Glargine; Insulin Secretion; Insulin, Long-Acting; Life Style; Middle Aged; Risk Factors; Time Factors

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

Insulin detemir is a soluble long-acting human insulin analogue at neutral pH with a unique mechanism of action. Following subcutaneous injection, insulin detemir binds to albumin via fatty acid chain, thereby providing slow absorption and a prolonged metabolic effect. Insulin detemir has a less variable pharmacokinetic profile than insulin suspension isophane or insulin ultralente. The use of insulin detemir can reduce the risk of hypoglycemia (especially nocturnal hypoglycemia) in type 1 and type 2 diabetic patients. However, overall glycemic control, as assessed by glycated hemoglobin, is only marginally and not significantly improved compared with usual insulin therapy. The weight gain commonly associated with insulin therapy is rather limited when insulin detemir is used. In our experience, this new insulin analogue is preferably administrated at bedtime but can be proposed twice a day (in the morning and either before the dinner or at bedtime). Detemir is a promising option for basal insulin therapy in type 1 or type 2 diabetic patients.

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Treatment Outcome; Weight Gain

To review the pharmacology, pharmacokinetics, clinical trial data, adverse effects, and role in therapy of insulin detemir.. Articles and meeting abstracts were identified through searches of MEDLINE (1996-June 2004), EMBASE (1980-June 2004), and International Pharmaceutical Abstracts (1970-June 2004) databases, and unpublished information was provided by the manufacturer.. All available studies relating to insulin detemir's pharmacology were selected. Only human studies were used for pharmacokinetic, drug interaction, efficacy, and safety data.. Insulin detemir is a basal insulin analog that has been shown to improve glycemic control in patients with type 1 and type 2 diabetes.. Insulin detemir offers some benefits over NPH for use as basal insulin in patients with type 1 and type 2 diabetes.

Topics: Blood Glucose; Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Patient Compliance; Weight Gain

After many decades of relative therapeutic stagnation since the initial discovery of insulin, followed by some modifications on its structure and only having sulfonylureas and biguanides for many years, the last decade has seen a surge in new therapeutic options for the management of diabetes. The results of the United Kingdom Prospective Diabetes Study and Kumamoto study indicate the need for aggressive glycemic control and the slow inexorable clinical deterioration associated with type 2 diabetes overtime. The propensity for weight gain and hypoglycemia are the two major limitations that subcutaneous insulin and sulfonylureas have been particularly prone to. The newer antidiabetic medications and those on the horizon attempt to address these limitations. GLP-1 agonists and the DPP-IV inhibitors exploit the innate incretin system to improve glycemia while promoting satiety and weight management. Like GLP-1 related compounds, pramlintide offers the potential to address postprandial hyperglucagonemia associated with type 2 diabetes only limited by the multiple injections and gastrointestinal side effects. The glitazars offer the hope ofa new approach to diabetes care addressing not just glycemia, but dyslipidemia and other components of the metabolic syndrome, though the side effect profile remains a major unknown. The INGAP peptide represents the holy grail of diabetes care as it offers the potential of a new paradigm: that of islet regeneration and potential for a cure. But at this stage, with no human data available, it remains highly speculative. Beyond these and other novel agents being developed to meet the challenge of the worldwide epidemic of diabetes, the central place of insulin in diabetes care cannot be forgotten. In view of this the continued efforts of improvement in insulin delivery, kinetics and action have spurred such innovations as the various inhaled insulins and new insulin analogues. There is cause for guarded optimism and excitement about the years ahead. There is reason to expect that despite the growing burden of diabetes worldwide, we will be better equipped to manage it and its comorbidities and prevent its onset and possibly even cure it.

Topics: Amyloid; Antigens, Neoplasm; Biomarkers, Tumor; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Dipeptidyl Peptidase 4; Glucagon; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Islet Amyloid Polypeptide; Lectins, C-Type; Pancreatitis-Associated Proteins; Peptide Fragments; Polymers; Protein Precursors; Thiazolidinediones

Topics: Diabetes Mellitus, Type 2; Humans; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin Lispro; 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

Insulin detemir (Levemir) is a soluble long-acting human insulin analogue acylated with a 14-carbon fatty acid. The fatty acid modification allows insulin detemir to reversibly bind to albumin, thereby providing slow absorption and a prolonged and consistent metabolic effect of up to 24 hours in patients with type 1 or type 2 diabetes mellitus. Insulin detemir has a more predictable, protracted and consistent effect on blood glucose than neutral protamine Hagedorn (NPH) insulin, with less intrapatient variability in glycaemic control, compared with NPH insulin or insulin glargine. Insulin detemir, administered once or twice daily, is at least as effective as NPH insulin in maintaining overall glycaemic control, with a similar or lower risk of hypoglycaemia, especially nocturnal hypoglycaemia, compared with NPH insulin in patients with type 1 or type 2 diabetes. Insulin detemir also provides the added clinical benefit of no appreciable bodyweight gain in patients with type 1 diabetes and less bodyweight gain than NPH insulin in patients with type 2 diabetes. Insulin detemir is, therefore, a promising new option for basal insulin therapy in patients with type 1 or 2 diabetes.

Topics: Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting

Insulin detemir (NN-304) is a soluble, long-acting insulin analog being developed by Novo Nordisk for the potential treatment of type 1 and 2 diabetes. As of February 2003, Novo Nordisk was expecting both US and EU approval in the first half of 2004. In December 2002, Novo Nordisk submitted an NDA to the FDA and an NDS to the Canadian Biologics & Genetics Therapeutic Directorate for the approval of insulin detemir for the treatment of diabetes mellitus.

Topics: Animals; Carrier Proteins; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Structure-Activity Relationship

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 therapy is ultimately necessary for the control of blood glucose in a majority of patients with type 2 diabetes mellitus. Unfortunately, the pharmacokinetic characteristics of previously available rapid-, intermediate-, and long-acting preparations make sustained normoglycemia almost impossible. Advances in molecular genetic engineering have made possible the development of insulin analogues with pharmacokinetics that more closely mimic the needs of patients with type 2 diabetes. In the following article, we explore the insulin analogues currently available for clinical use, their pharmacokinetics, and the rationale for their use in the treatment of type 2 diabetes, and follow-up with a brief examination of future developments.

Topics: Administration, Inhalation; Administration, Oral; Carrier Proteins; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting

To explore the effect of active insulin titration versus usual titration on glycaemic control in patients with type 2 diabetes mellitus uncontrolled with oral antidiabetic drugs (OADs).. In a 24-week, prospective and randomized study, 172 patients with uncontrolled type 2 diabetes were randomly assigned to either active titration or usual titration. Efficacy and safety outcomes included changes in glycated haemoglobin (HbA1c) and fasting plasma glucose, percentage of individuals achieving HbA1c<53 mmol/mol, and hypoglycaemic events.. At Week 24, change in HbA1c was -1.08% ± 1.60% in the active titration group and -0.95% ± 1.34% in the usual titration group (P = 0.569). The percentages of individuals achieving HbA1c<53 mmol/mol were 29.4% and 16.1% in the active and usual titration groups, respectively (P = 0.037). There was no significant difference in the incidence of hypoglycaemia between the two groups. Multivariate logistic regression indicated that, with active titration, baseline HbA1c levels and postprandial glucose excursion were significantly associated with achieving HbA1c<53 mmol/mol.. Addition of basal insulin using active titration for 24 weeks provided a higher rate of HbA1c target achievement without significant hypoglycaemia compared to usual titration in individuals with uncontrolled type 2 diabetes.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Prospective Studies

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

This study was conducted to compare glycaemic control with insulin detemir administered according to two titration algorithms (3-0-3 and 2-4-6-8) after 20 weeks of treatment in subjects with type 2 diabetes mellitus inadequately controlled on metformin.. This was a 20-week, randomised, multicentre, open-labelled, treat-to-target trial. Forty-six patients were randomised in a 1:1 manner to either the 3-0-3 (G3,. Both treatment groups had numerically similar HbA1c reductions. A trend towards fewer hypoglycaemia episodes after dose stabilisation was seen with the simpler G3. Clinically, this may be an important observation, as a simpler titration algorithm may support self-management and maintenance of insulin therapy.

Topics: Adult; Aged; Algorithms; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Detemir; Male; Middle Aged; Prognosis

Type 2 diabetes (T2D) is a long-term metabolic disorder. A pilot trial was designed to investigate the effects of the long acting insulin Detemir on endogenous insulin secretion, to assess use in early T2D care. Provesn metabolic system models are used to identify patient-specific insulin sensitivity and endogenous insulin secretion from clinical data. Post-cardiac surgery patients with early T2D or pre-diabetes based on HbA1c were given a bolus of insulin Detemir on one day, and none on the second day in hospital. Blood glucose, insulin, C-Peptide, and all nutrition given are recorded. Early results from N=3 patients show 0.8-1.0U/hour insulin Detemir doses have no apparent suppression of endogenous insulin secretion, but does help lower glucose levels. The results show the model captures glucose-insulin dynamics in pre-diabetic post-surgical patients, and insulin Detemir may be useful to support individuals with pre-diabetes in reducing blood glucose levels. Tests with higher doses, need to be carried out to verify these results over a greater range of patients.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Male; Models, Theoretical; Pilot Projects

To compare the efficacy and safety of a glucagon-like peptide-1 receptor agonist (GLP1RA) plus basal insulin versus basal-bolus insulin treatment in patients with very uncontrolled type 2 diabetes.. The SIMPLE study was a 6-month pragmatic, randomized, open-label trial testing the effectiveness of two approaches to treat patients with type 2 diabetes and HbA1c ≥10%. We randomized patients to detemir plus liraglutide or detemir plus aspart (before each meal). The primary endpoint was change in HbA1c; changes in body weight, insulin dose, hypoglycaemia and diabetes-related quality-of-life were secondary outcomes.. In patients with HbA1c ≥10% treatment with GLP1RA plus basal insulin, compared with basal-bolus insulin, resulted in better glycaemic control and body weight, lower insulin dosage and hypoglycaemia, and improved quality of life. This treatment strategy is an effective and safe alternative to a basal-bolus insulin regimen.

Topics: Adult; Blood Glucose; Body Weight; Comparative Effectiveness Research; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin Detemir; Liraglutide; Male; Meals; Middle Aged; Treatment Outcome

A single insulin injection was shown to improve microcirculatory blood flow. Our aim was to examine the effects of 4weeks of insulin therapy by three randomly assigned insulin analog regimens (Detemir, Aspart, and their combination) on cutaneous blood flow (CBF) and microcirculatory endothelial function as an add-on to metformin in type 2 diabetic patients poorly controlled on oral antidiabetic treatment.. Fourty-two type 2 diabetic patients with no history of cardiovascular disease in secondary failure to oral antidiabetic agents had CBF measurements before and after acetylcholine (Ach) iontophoretic administration. CBF measurements were performed at fasting and after a standardized breakfast during the post-prandial period. Before randomization (Visit 1, V1) during the tests, participants took only metformin. The same tests were repeated after 4weeks of insulin treatment (Visit 2, V2).. Thirty-four patients had good quality recordings for both visits. During V1, CBF and CBF response to Ach increased in the post-prandial period. After 4weeks of insulin treatment, metabolic parameters improved. Compared to V1, CBF at fasting did not increase at V2 but there was an improvement in endothelial function at fasting after Ach iontophoresis, without difference across insulin regimens. Oxidative stress markers were not modified, and E-selectin and vascular cell adhesion molecule 1 levels decreased after insulin treatment, without differences between insulin groups.. A strategy of improving glycemic control for 4weeks with insulin analogs improves microcirculatory endothelial reactivity and reduces endothelial biomarkers at fasting, whatever the insulin regimen used. Insulin therapy associated to metformin is able to improve fasting microvascular endothelial function even before complete metabolic control.

Topics: Administration, Cutaneous; Adult; Aged; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Endothelium, Vascular; Female; France; Humans; Hypoglycemic Agents; Insulin Aspart; Insulin Detemir; Iontophoresis; Male; Metformin; Microcirculation; Middle Aged; Pilot Projects; Regional Blood Flow; Skin; Time Factors; Treatment Outcome; Vasodilator Agents

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

It is unclear if effects of glucagon-like peptide-1 (GLP-1) and clinically available GLP-1 agonists on the heart occur at clinical doses in humans, possibly contributing to reduced cardiovascular disease risk.. To determine whether liraglutide, at clinical dosing, augments myocardial glucose uptake (MGU) alone or combined with insulin compared with insulin alone in metformin-treated type 2 diabetes mellitus (T2D).. In a randomized clinical trial of patients with T2D treated with metformin plus oral agents or basal insulin, myocardial fuel use was compared after 3 months of treatment with insulin detemir, liraglutide, or combination detemir plus liraglutide added to background metformin.. Myocardial blood flow (MBF), fuel selection, and rates of fuel use were evaluated using positron emission tomography, powered to demonstrate large effects.. MBF was greater in the insulin-treated groups [median (25th, 75th percentile): detemir, 0.64 mL/g/min (0.50, 0.69); liraglutide, 0.52 mL/g/min (0.46, 0.58); detemir plus liraglutide, 0.75 mL/g/min (0.55, 0.77); P = 0.035 comparing three groups, P = 0.01 comparing detemir groups to liraglutide alone]. There were no evident differences among groups in MGU [detemir, 0.040 µmol/g/min (0.013, 0.049); liraglutide, 0.055 µmol/g/min (0.019, 0.105); detemir plus liraglutide, 0.037 µmol/g/min (0.009, 0.046); P = 0.68 comparing three groups]. There were no treatment-group differences in measures of myocardial fatty acid uptake or handling, and no differences in total oxidation rate.. These observations argue against large effects of GLP-1 agonists on myocardial fuel metabolism as mediators of beneficial treatment effects on myocardial function and ischemia protection.

Topics: Adult; Blood Glucose; Coronary Circulation; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Heart; Humans; Hypoglycemic Agents; Insulin Detemir; Liraglutide; Male; Metformin; Middle Aged; Myocardium; Treatment Outcome

Despite their widespread use in this population, data on the pharmacodynamic (PD) properties of the insulin analogs detemir and glargine in severely obese patients with type 2 diabetes are lacking.. The primary objective of the study was to compare the PD properties of two different doses of the basal insulin analogs detemir and glargine in patients with type 2 diabetes and a BMI > 35 kg/m2. PD data were derived from euglycemic clamp studies over 30 hours and each subject was studied for four times after the subcutaneous injection of a lower (0.8 U/kg body weight) and higher (1.6 U/kg body weight) dose of both detemir and glargine using a single-blind, randomised cross-over design.. Six male and four female patients with type 2 diabetes and a mean BMI of 43.2±5.1 kg/m2 (mean age 55.7±2 years, mean HbA1c 7.2±0.3%) completed the study. The total GIRAUC0-30 (mean difference 1224 mg/kg, 95%CI 810-1637, p = 0.00001), GIRAUC0-24 (mean difference 1040 mg/kg, 95%CI 657-1423; p = 0.00001), GIRAUC24-30 (mean difference 181 mg/kg, 95%CI 64-298; p = 0.004), GIRmax (mean difference 0.93 mg/kg/min, 95%CI 0.22-1.64, p = 0.01) and time to GIRmax (+1.9 hours, 95%CI 0.5-3.2; p = 0.009) were higher after the higher doses of both insulins, without significant differences between detemir and glargine. However, during the last 6 hours of the clamp the GIRAUC24-30 was significantly increased with glargine (mean difference 122 mg/kg, 95%CI 6-237, p = 0.043), reflecting a more pronounced late glucose lowering effect.. A clear dose-response relationship can be demonstrated for both insulin analogs, even at very high doses in severely obese patients with type 2 diabetes. Compared to detemir, glargine has a more pronounced late glucose lowering effect 24-30 h after its injection.. Controlled-Trials.com ISRCTN57547229.

Topics: Adult; Biomarkers; Blood Glucose; C-Peptide; Cross-Over Studies; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Glucose Clamp Technique; Humans; Insulin Detemir; Insulin Glargine; Male; Middle Aged; Obesity

Clinical outcome may differ owing to the distinct pharmacological characteristics of insulin sensitizers and insulin. This study was performed to compare the metabolic and renal function changes with add-on pioglitazone treatment versus basal insulin in patients with type 2 diabetes mellitus (DM) in whom sulfonylurea and metformin regimens failed.. Patients who were consecutively managed in the diabetes comprehensive program with add-on pioglitazone or detemir/glargine treatment for at least 2 years following sulfonylurea and metformin treatment failure were included.. A total of 1002 patients were enrolled (pioglitazone: 559, detemir: 264, glargine: 179). After propensity score matching, there were 105 patients with matchable baseline characteristics in each group. After a mean of 3.5 years of follow-up, the pioglitazone group showed a greater HbA1c reduction than the detemir group and the glargine group. Despite patients in all three groups exhibiting significant body weight gain, those in the pioglitazone group and the glargine group showed greater body weight increases than the patients in the detemir group (2.1, 1.6 and 0.8 kg, respectively, p < 0.05). Interestingly, Cox regression analysis indicated that patients under detemir or glargine treatment had a higher probability of CKD progression as compared with the pioglitazone group, with hazard ratios of 2.63 (95% CI 1.79-3.88) and 3.13 (95% CI 2.01-4.87), respectively.. Our study first showed that treatment with both pioglitazone and basal insulin improved glycemic control, while only pioglitazone treatment was observed to be advantageous in terms of preserving renal function when used as an add-on therapy for patients with type 2 DM in whom sulfonylurea and metformin regimens failed.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Drug Therapy, Combination; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Detemir; Kidney; Kidney Function Tests; Middle Aged; Pioglitazone; Thiazolidinediones; Treatment Outcome

To confirm glycaemic control superiority of mealtime fast-acting insulin aspart (faster aspart) in a basal-bolus (BB) regimen vs basal-only insulin.. In this open-label, randomized, 18-week trial (51 sites; 6 countries), adults (n = 236) with inadequately controlled type 2 diabetes (T2D; mean glycosylated haemoglobin [HbA1c] ± SD: 7.9% ± 0.7% [63.1 ± 7.5 mmol/mol]) receiving basal insulin and oral antidiabetic drugs underwent 8-week optimization of prior once-daily basal insulin followed by randomization 1:1 to either a BB regimen with faster aspart (n = 116) or continuation of once-daily basal insulin (n = 120), both with metformin. Primary endpoint was HbA1c change from baseline after 18 weeks of treatment. Secondary endpoints included: postprandial plasma glucose (PPG) change and overall PPG increment (all meals); weight; treatment-emergent adverse events; hypoglycaemic episodes.. HbA1c decreased from 7.9% (63.2 mmol/mol) to 6.8% (50.7 mmol/mol; BB group) and from 7.9% (63.2 mmol/mol) to 7.7% (60.7 mmol/mol; basal-only group); estimated treatment difference [95% confidence interval] -0.94% [-1.17; -0.72]; -10.3 mmol/mol [-12.8; -7.8]; P  < .0001. Reductions from baseline in overall mean 2-hour PPG and overall PPG increment for all meals (self-measured plasma glucose profiles) were statistically significant in favour of BB treatment ( P  < .0001). Severe/blood glucose confirmed hypoglycaemia rate (12.8 vs 2.0 episodes per patient-years of exposure), total daily insulin (1.2 vs 0.6 U/kg) and weight gain (1.8 vs 0.2 kg) were greater with BB than with basal-only treatment.. In T2D, faster aspart in a BB regimen provided superior glycaemic control as compared with basal-only insulin, but with an increase in the frequency of hypoglycaemia and modest weight gain.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Insulin Aspart; Insulin Detemir; Male; Middle Aged

The aim of the present study is to quantitatively assess the expression of selected regulatory molecules, such as leptin, leptin receptor, and adiponectin in the blood of obese patients with type 2 diabetes both before treatment and after six months of pharmacological therapy with the long-lasting insulin analogue, insulin detemir. A significant decrease in the analysed regulatory molecules, i.e., leptin receptor and adiponectin, was found in blood plasma of the patients with untreated type 2 diabetes. These changes were accompanied by an increase in plasma leptin concentrations. Insulin treatment resulted in the normalization of plasma leptin receptor and adiponectin concentrations. The circulating leptin level did not change following anti-diabetic therapy with insulin detemir. Gender was a significant factor modifying the circulating level of all the analysed regulatory active compounds. Bioinformatic analysis was performed using Matlab with the Signal Processing Toolbox. The conducted discriminant analysis revealed that the leptin receptor, Δw(19), and adiponectin, Δw(21), were the parameters undergoing the most significant quantitative changes during the six-month therapy with insulin detemir. The conducted examinations indicated the contribution of adipocytokines-the biologically-active mediators of systemic metabolism, such as leptin and adiponectin in the pathomechanism of disorders being the basis for obesity which leads to development of insulin resistance, which, in turn, results in the occurrence of type 2 diabetes.

Topics: Adiponectin; Adult; Aged; Diabetes Mellitus, Type 2; Female; Humans; Insulin Detemir; Leptin; Male; Middle Aged; Obesity; Receptors, Leptin; Sex Factors

Weight gain is an ongoing challenge when initiating insulin therapy in patients with type 2 diabetes mellitus (T2DM). However, if prediction of insulin-associated weight gain was possible on an individual level, targeted initiatives could be implemented to reduce weight gain. The aim of the present study was to identify predictors of weight gain in insulin-treated patients with T2DM.. In all, 412 individuals with T2DM were, in addition to metformin or placebo, randomized into 18-month treatment groups with three different insulin analog treatment regimens (biphasic, aspart, detemir). Participants with excessive weight gain were defined as the group with weight gain in the 4th quartile (>6.2 kg).We developed a pattern classification method to predict individuals prone to excessive weight gain.. Over the 18-month treatment period, median weight gain among all 412 patients was 2.4 kg (95% prediction interval [PI] -5.6, 12.4 kg), whereas median weight gain for those in the upper 4th quartile (n = 103) was 8.9 kg (95% PI 6.3, 15.2 kg). No clinical baseline data were strong predictors of excessive weight gain. However, the weight gain during the first 3 months of the trial and the subsequent dose of insulin yielded a useful predictor for weight gain at the 18-month follow-up. Combining these two predictors into a prediction model with other clinical available information produced a receiver operating characteristic area under the curve of 0.80.. We have developed a prediction model that could help identify a substantial proportion of individuals with T2DM prone to large weight gain during insulin therapy.

Topics: Aged; Biphasic Insulins; Blood Glucose; Chi-Square Distribution; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Aspart; Insulin Detemir; Logistic Models; Male; Metformin; Middle Aged; Prognosis; Time Factors; Treatment Outcome; Weight Gain

The aim of the study was to compare body composition and epicardial fat thickness changes in insulin-naïve inadequately controlled patients with type 2 diabetes following basal insulin initiation with detemir vs. glargine. Six-month, open-label, interventional randomized pilot study was conducted. Dual-energy X-ray absorptiometry and echocardiography were used to estimate the body composition and epicardial fat thickness respectively. Thirty-six patients in the detemir group and 20 in the glargine group completed the study. Study groups baseline characteristics were comparable. At 6 months, for similar glycemic control, those on detemir significantly gained less total weight (0.6±2.5 vs. 4.2±4.1 kg, p=0.004), total fat mass (0.9±2.2 vs. 2.9±2.4 kg, p=0.02), and truncal fat mass (0.8±1.5 vs. 2.1±1.7 kg, p=0.02), with a loss in truncal lean mass (- 0.8±1.9 kg vs. 0.3±1.7 kg; p=0.02). EFT significantly decreased from baseline in both group (detemir - 1.7±0.52-mm, glargine - 1.1±1.6-mm; p<0.05, without significant difference inter-groups). Within the detemir group, epicardial fat thickness change correlated with truncal fat and total fat mass changes (r=0.65, p=0.06 and r=0.60, p=0.07). In conclusion, detemir resulted in less fat mass gain, a trend for a more pronounced epicardial fat thickness reduction when compared with glargine.

Topics: Adiposity; Blood Glucose; Body Composition; Body Weight; Diabetes Mellitus, Type 2; Female; Humans; Insulin Detemir; Insulin Glargine; Male; Middle Aged; Pericardium

To evaluate the efficacy and safety of two insulin intensification strategies for patients with type 2 diabetes previously treated with basal insulin--insulin degludec (IDeg) and insulin aspart (IAsp)--administered as a co-formulation (IDegAsp) or as a basal-bolus regimen (IDeg and IAsp in separate injections).. This 26-week, open-label, treat-to-target, phase IIIb, non-inferiority trial randomized patients (1 : 1) to IDegAsp twice daily with main meals (n = 138; IDegAsp group) or IDeg once daily and IAsp 2-4 times daily (n = 136; IDeg+IAsp group).. After 26 weeks, the mean glycated haemoglobin (HbA1c) level was 7.0% (53 mmol/mol) for the IDegAsp group and 6.8% (51 mmol/mol) for the IDeg+IAsp group (Δ%HbA1c from baseline -1.31 and -1.50%, respectively). The non-inferiority of IDegAsp versus IDeg+IAsp was not confirmed for mean change in HbA1c [estimated treatment difference (ETD) 0.18, 95% confidence interval (CI) -0.04, 0.41; p = non-significant]. No significant differences were observed in the proportion of patients achieving HbA1c <7.0% (56.5 and 59.6%, respectively). IDegAsp treatment resulted in a significantly lower total daily insulin dose, a smaller change in body weight, numerically lower rates of confirmed hypoglycaemia (self-reported plasma glucose <3.1 mmol/l; rate ratio 0.81; p = non-significant), and nocturnal confirmed hypoglycaemic episodes (rate ratio 0.80; p = non-significant) versus IDeg+IAsp. Patient-reported outcome scores for social functioning were significantly higher for IDegAsp versus IDeg+IAsp (ETD 2.2; 95% CI 0.3, 4.1; p < 0.05).. Both intensification strategies effectively improved glycaemic control. Although non-inferiority was not confirmed, there were no significant differences between the groups that could affect clinical utility.

Topics: Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin Detemir; Insulin, Long-Acting; Male; Meals; Middle Aged

To compare the efficacy and safety of insulin glargine 300 U/ml (Gla-300) with glargine 100 U/ml (Gla-100) in Japanese people with type 2 diabetes using basal insulin plus oral antihyperglycaemic drug(s) [OAD(s)].. The EDITION JP 2 study (NCT01689142) was a 6-month, multicentre, open-label, phase III study. Participants (n = 241, male 61%, mean diabetes duration 14 years, mean weight 67 kg, mean body mass index 25 kg/m(2), mean glycated haemoglobin (HbA1c) 8.02 %, mean basal insulin dose 0.24 U/kg/day) were randomized to Gla-300 or Gla-100, while continuing OAD(s). Basal insulin was titrated to target fasting self-monitored plasma glucose 4.4-5.6 mmol/l. The primary efficacy endpoint was HbA1c change over 6 months. Safety endpoints included hypoglycaemia and weight change.. Gla-300 was non-inferior to Gla-100 for HbA1c reduction [least squares (LS) mean difference 0.10 (95% confidence interval [CI] -0.08, 0.27) %]. The mean HbA1c at month 6 was 7.56 and 7.52 % with Gla-300 and Gla-100, respectively. Nocturnal confirmed (≤3.9 mmol/l) or severe hypoglycaemia risk was 38% lower with Gla-300 versus Gla-100 [relative risk 0.62 (95% CI 0.44, 0.88)]; annualized rates were 55% lower at night [rate ratio 0.45 (95% CI 0.21, 0.96)] and 36% lower at any time [24 h; rate ratio 0.64 (95% CI 0.43, 0.96)]. Severe hypoglycaemia was infrequent. A significant between-treatment difference in weight change favoured Gla-300 [LS mean difference -1.0 (95% CI -1.5, -0.5) kg; p = 0.0003]. Adverse event rates were comparable between groups.. Japanese people with type 2 diabetes using basal insulin plus OAD(s) experienced less hypoglycaemia with Gla-300 than with Gla-100, while glycaemic control did not differ.

Topics: Administration, Oral; Aged; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Resistance, Multiple; Drug Therapy, Combination; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Japan; Male; Middle Aged; Risk

The prevention of cardiovascular disease, including diastolic cardiac dysfunction with its high prevalence and ominous prognosis, is a therapeutic challenge for patients with type 2 diabetes. Both short and long-acting insulin analogues (AI) have been shown to reduce glucose variability and provide potential benefit for cardiovascular disease although the effects on cardiac function have not yet been evaluated. This long-term, prospective, randomized controlled trial in patients with type 2 diabetes (T2D) tested the hypothesis that a multiple daily injection regimen (MDI) with AI improves postmeal glucose excursions in comparison to human insulin (HI) and that the effects of AI improve diastolic cardiac function.. For 36 months, MDI treatment in 109 T2D patients was adapted every 3 months (targets: fasting glucose ≤ 110 mg/dl, postmeal glucose ≤ 150 mg/dl) in both groups: AI (insulin detemir and insulin aspart, n = 61) and HI (NPH-insulin and regular HI, n = 48). Diastolic cardiac function (myocardial velocity E' using tissue Doppler imaging and the mitral inflow ratio E/A) and vascular function were assessed before and 2 h after a standardized breakfast (48 g carbohydrates). At baseline, both groups were comparable with regards to demographic, cardiac and metabolic data. Analysis of data included traditional statistics as well as the use of a multiple imputation technique shown in brackets [ ].. At 36 months, the primary endpoint, postmeal glucose, decreased by 20 ± 62 mg/dl, p = 0.038 [p = 0.021] with AI and increased insignificantly with HI (inter-group p = 0.032 [p = 0.047]) to postmeal glucose levels of 161 ± 39 with AI vs. 195 ± 54 mg/dl with HI (inter-group p = 0.002 [p = 0.010]) whereas the levels of fasting glucose and HbA1c were comparable. With AI, postmeal E' improved by 0.6 ± 1.4 cm/s, p = 0.009 [p = 0.002] and fasting E' by 0.4 ± 1.4 cm/s, p = 0.069 [p = 0.013], however, E' remained unchanged with HI. These changes were consistent with those of the traditional parameter E/A.. MDI with AI results in better postmeal glucose control compared to HI. The treatment with AI is associated with improved diastolic cardiac function. ClinicalTrials.gov (NTC00747409).

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Diastole; Drug Administration Schedule; Echocardiography, Doppler, Pulsed; Female; Germany; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Injections; Insulin Aspart; Insulin Detemir; Male; Middle Aged; Postprandial Period; Prospective Studies; Time Factors; Treatment Outcome; Ventricular Function, Left

Previous studies comparing insulin detemir versus insulin glargine showed conflicting results, and included only outpatients. This study compared the two insulin analogs once daily in hospitalized patients with type 2 diabetes (T2D).. A total of 55 patients aged 18-80 years with hyperglycemia admitted to the endocrinology wards were screened between June 2014 and February 2015. Forty-two enrolled patients were randomly assigned to receive either insulin detemir followed by insulin glargine once daily (n = 21), or vice versa (n = 21). The two insulin analogs were titrated 0.1 U/kg once daily based on fasting blood glucose (FBG). After achieving FBG <7.8 mmol/L (the first period), subjects were switched from one analog to the other (the second period) with no change in the dose. The second period lasted for 3 days. When hypoglycemia occurred in the second period, the observation was discontinued. Six-point blood glucose including FBG, 2 h after breakfast, lunch, dinner, bedtime, and at 3:00 am was tested every day. The glucose profiles of the final days in the two periods were compared.. At the end of the first period, days for achieving FBG target (4.0 ± 0.5 days vs. 3.3 ± 0.4 days, t = 1.079, P = 0.286) and total daily dose (30.1 ± 2.4 U vs. 30.1 ± 2.9 U, t = 0.002, P = 0.999) between insulin detemir and insulin glargine were similar. There was no significant difference in the 24-h glucose control between the two analogs. No hypoglycemia occurred with both analogs in the first period. However, in the second period, when insulin glargine was switched to insulin detemir, two, three and, one patients had hypoglycemia events on day 1, day 2 and day 3 of the second period, respectively. One patient had severe hypoglycemia on day 1.. When both basal insulin analogs were given once daily in T2D, insulin detemir achieved similar efficacy to insulin glargine. On the other hand, there may be differences in action of the compared basal insulins. Further studies with larger patient samples are necessary to support evidence and reveal possible mechanisms.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Female; Hospitalization; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Male; Middle Aged; Young Adult

This post-hoc sub-analysis investigated whether age (<65 years vs ≥65 years) affects glycemic control or hypoglycemic risk in patients with type 2 diabetes mellitus (T2DM) treated with once-daily insulin detemir.. This was a 26-week, randomized, open-label, phase IV trial involving 2812 patients at 1083 predominantly primary care sites throughout the United States, of which 541 were designated for investigator-led insulin titration. The main efficacy measure was change in HbA1c (A1C) from baseline to Week 26. Patients were stratified by age in the sites designated for the investigator-led titration of insulin detemir. Safety measures included adverse events and change in hypoglycemic event rates from baseline to Week 26.. At Week 26, mean A1C and fasting plasma glucose decreased in both groups, but mean differences in change from baseline were not significant between groups. Within the group ≥65 years, significant reductions occurred for all daytime hypoglycemia, but there was no significant change from baseline in the other categories. In the group <65 years, reductions from baseline were significant for all hypoglycemic event categories. Changes in hypoglycemia rates from baseline were not significantly different between the age groups and there was no weight increase in either age group.. This analysis demonstrates that insulin detemir has similar efficacy and safety profiles for patients with T2DM ≥65 years compared with <65 years when treated via an investigator-led algorithm.

Topics: Adult; Aged; Algorithms; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Male; Middle Aged; Treatment Outcome; United States

To investigate the effect of healthcare provider (HCP) type (primary vs. specialist) on glycaemic control and other treatment parameters.. Study of Once-Daily Levemir (SOLVE(™) ) is an international, 24-week, observational study of insulin initiation in people with type 2 diabetes.. A total of 17,374 subjects were included, comprising 4144 (23.9%) primary care subjects. Glycaemic control improved in both HCP groups from baseline to final visit [glycated haemoglobin (HbA1c) -1.2 ± 1.4% (-13.1 ± 15.3 mmol/mol) and -1.3 ± 1.6% (-14.2 ± 17.5 mmol/mol), respectively]. After adjustment for known confounders, there was no statistically significant effect of HCP group on final HbA1c [-0.04%, 95% confidence interval (CI) -0.09 to -0.01 (-0.4 mmol/mol, 95% CI -1.0-0.1 mmol/mol), p = 0.1590]. However, insulin doses at the final visit were higher in primary care patients (+0.06, 95% CI 0.06-0.07 U/kg, p < 0.0001). Logistic regression demonstrated a significant effect of HCP type (primary vs. specialist care) on hypoglycaemia risk [odds ratio (OR) 0.75, 95% CI 0.64-0.87, p = 0.0002]. Primary care physicians took more time to train patients and had more frequent contact with patients than specialists (both p < 0.0001).. Primary care physicians and specialists achieved comparable improvements in glycaemic control following insulin initiation.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Logistic Models; Male; Middle Aged; Primary Health Care; Prospective Studies; Treatment Outcome

To assess the effect of 3 insulin analogue regimens on change in carotid intima-media thickness (IMT) in patients with type 2 diabetes.. Investigator-initiated, randomised, placebo-controlled trial with a 2 × 3 factorial design, conducted at 8 hospitals in Denmark.. Participants with type 2 diabetes (glycated haemoglobin (HbA1c) ≥ 7.5% (≥ 58 mmol/mol), body mass index >25 kg/m(2)) were, in addition to metformin versus placebo, randomised to 18 months open-label biphasic insulin aspart 1-3 times daily (n=137) versus insulin aspart 3 times daily in combination with insulin detemir once daily (n=138) versus insulin detemir alone once daily (n=137), aiming at HbA1c ≤ 7.0% (≤ 53 mmol/mol).. Primary outcome was change in mean carotid IMT (a marker of subclinical cardiovascular disease). HbA1c, insulin dose, weight, and hypoglycaemic and serious adverse events were other prespecified outcomes.. Carotid IMT change did not differ between groups (biphasic -0.009 mm (95% CI -0.022 to 0.004), aspart+detemir 0.000 mm (95% CI -0.013 to 0.013), detemir -0.012 mm (95% CI -0.025 to 0.000)). HbA1c was more reduced with biphasic (-1.0% (95% CI -1.2 to -0.8)) compared with the aspart+detemir (-0.4% (95% CI -0.6 to -0.3)) and detemir (-0.3% (95% CI -0.4 to -0.1)) groups (p<0.001). Weight gain was higher in the biphasic (3.3 kg (95% CI 2.7 to 4.0) and aspart+detemir (3.2 kg (95% CI 2.6 to 3.9)) compared with the detemir group (1.9 kg (95% CI 1.3 to 2.6)). Insulin dose was higher with detemir (1.6 IU/kg/day (95% CI 1.4 to 1.8)) compared with biphasic (1.0 IU/kg/day (95% CI 0.9 to 1.1)) and aspart+detemir (1.1 IU/kg/day (95% CI 1.0 to 1.3)) (p<0.001). Number of participants with severe hypoglycaemia and serious adverse events did not differ.. Carotid IMT change did not differ between 3 insulin regimens despite differences in HbA1c, weight gain and insulin doses. The trial only reached 46% of planned sample size and lack of power may therefore have affected our results.. NCT00657943.

Topics: Blood Glucose; Body Weight; Carotid Intima-Media Thickness; Denmark; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Male; Metformin; Middle Aged; Treatment Outcome

To compare the effects of the basal insulin analogues glargine and detemir on endothelial function and adipocytokine levels in people with Type 2 diabetes.. We studied 32 people with Type 2 diabetes whose blood glucose control was unsatisfactory while receiving only oral hypoglycaemic drugs. Participants were randomized to either insulin glargine or detemir for 24 weeks and then crossed over to the other treatment without a washout period. Flow-mediated vasodilatation, adipocytokine levels (plasminogen activator inhibitor-1 and leptin/adiponectin ratio), and fasting ghrelin levels were monitored.. These results suggest that the effect on endothelial function and adipocytokine profiles may differ between glargine and detemir in people with diabetes (Trial registration ID: UMIN000004973).

Topics: Adipokines; Adiponectin; Adult; Aged; Ankle Brachial Index; C-Reactive Protein; Cross-Over Studies; Diabetes Mellitus, Type 2; Endothelium, Vascular; Female; Ghrelin; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Leptin; Male; Middle Aged; Obesity; Plasminogen Activator Inhibitor 1; Vasodilation; Young Adult

Topics: Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Glycated Hemoglobin; Humans; Insulin Aspart; Insulin Detemir

This study aims to compare the effectiveness of insulin glargine 300 U/mL (Gla-300) with its accompanying patient support program with that of other basal insulin and available patient support programs in patients with type 2 diabetes (T2D) in a real-world setting in terms of achieving HEDIS (Healthcare Effectiveness Data and Information Set) individualized glycemic targets without documented symptomatic hypoglycemia.. Achieve Control is a US-based, multicenter, randomized, open-label, active-controlled, parallel group pragmatic Phase IV trial in insulin-naïve patients with T2D uncontrolled on ≥2 oral antidiabetes drugs (OAD) and/or glucagon-like peptide-1 receptor antagonists (GLP-1 RA). Inclusion criteria include a diagnosis of T2D, age ≥18 years, and glycated hemoglobin (HbA1c) between 8.0% and 11.0%. Patients will be assigned to either the Gla-300 or other basal insulin group. The primary end point is the proportion of patients achieving HEDIS HbA1c targets (<8.0% [64 mmol/mol] in patients with comorbidities or aged ≥65 years; <7.0% [58 mmol/mol] in all other patients) without occurrence of symptomatic hypoglycemia (blood glucose ≤70 mg/dL) from baseline to 6 months. Secondary end points include rates of documented symptomatic nocturnal hypoglycemia and severe hypoglycemia; change from baseline in HbA1c, fasting glucose, and body weight; treatment persistence; patient-reported outcomes; and healthcare resource utilization. Planned enrollment is 3270 patients across approximately 400 clinical sites.. Pragmatic clinical trials offer the potential to assess comparative effectiveness in broadly based patient populations receiving care (with or without a corresponding educational support program) in real-world clinical settings. The results of Achieve Control should elucidate the benefits of management of T2D with Gla-300 versus other basal insulins in terms of patient outcomes, experiences, and perceptions, and its impact on healthcare resource utilization and cost.. www.clinicaltrials.gov identifier is NCT02451137.

Topics: Aged; Blood Glucose; Body Weight; Comorbidity; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Health Services; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Male; Patient Reported Outcome Measures; United States

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

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

This study aimed to compare the efficacy and safety of liraglutide versus insulin detemir plus sitagliptin in Japanese patients with type 2 diabetes treated with a basal-bolus insulin regimen. In this multicenter, open-label trial, 90 patients whose diabetes had been controlled well or moderately (glycated hemoglobin [HbA1c ] ≤ 7.3%) with basal-bolus insulin regimen were randomly assigned to a liraglutide group or a detemir group and were followed up for 24 weeks. The primary end point was HbA1c change from baseline to 24 weeks. Of the 90 enrolled patients, 82 completed this trial. At 24 weeks, the mean changes in HbA1c from baseline were 0.1% ± 0.9% versus 0.3% ± 0.8% in the liraglutide versus detemir groups, respectively (P = .46). The "overall" satisfaction score for the Diabetes Treatment Satisfaction Questionnaire changed from 25.2 ± 7.4 to 29.9 ± 5.3 (P < .001) and from 26.4 ± 6.1 to 28.3 ± 6.4 (P = .12) in the liraglutide and detemir groups, respectively. Although the mean change difference in HbA1c between both groups was not significant, switching from a basal-bolus insulin regimen to liraglutide once daily improved patient satisfaction levels without loss of glycemic control.

Topics: Aged; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Injections; Insulin Detemir; Japan; Liraglutide; Male; Middle Aged; Patient Satisfaction; Sitagliptin Phosphate; Surveys and Questionnaires; Treatment Outcome

Hypoglycemia is a barrier to the achievement of glycemic targets and limits the beneficial effects of improved glucose control on cardiovascular outcomes in type 2 diabetes (T2D). Circulating endothelial progenitor cells (EPCs) participate in cardiovascular homeostasis and predict future cardiovascular events. Therefore, we herein analyzed the association between occurrence of hypoglycemia and EPC changes in T2D patients after optimization of glucose control with basal insulin therapy.. In the NCT00699686 trial, 42 T2D insulin-naïve patients received a 3 + 3-month cross-over therapy with glargine and detemir. There were 43 minor and 2 severe hypoglycemic episodes in 19 patients (45.2 %, 0.54 episodes/patient/year). Changes in EPCs were analyzed in relation to the occurrence of hypoglycemia during the trial.. Patients with hypoglycemia had a higher final HbA1c at 6 months than patients without, although absolute HbA1c changes were not significantly different. Though PCs increased at study end, in patients experiencing at least 1 hypoglycemic episode, the changes in CD34(+), CD133(+) progenitor cells and CD34(+)KDR(+) EPCs were significantly lower than the respective changes in patients without incident hypoglycemia, even after correcting for confounders. During treatment with detemir, which induced >twofold less hypoglycemia than glargine, CD34(+)KDR(+) EPCs increased significantly more than during treatment with glargine.. In naïve T2D patients initiating basal insulin, hypoglycemia prevents the increase in vasculoprotective PCs. Clinically, these data strengthen the importance of avoiding hypoglycemia to improve cardiovascular outcomes during the treatment of T2D.

Topics: Aged; Cross-Over Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Endothelial Progenitor Cells; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Male; Middle Aged

To evaluate the safety and efficacy of insulin injections in patients using 8 mm 31 gauge vs. 5 mm 31 gauge pen needles, as determined by A1C results and to measure individual patient satisfaction and compare overall satisfaction regarding the use of the 2 needles.. The study was completed as a substudy of a single-site, open-label, randomized, 6-month comparative study consisting of 66 obese patients. Prior to the study, all individuals had treated their diabetes with either long-acting insulin glargine or insulin detemir. At the onset of the study, patients were randomized 1:1 to either insulin glargine or neutral protamine Hagedorn insulin. All patients used an 8 mm pen needle for the first 3 months and a 5 mm pen needle for the remaining 3 months. At the conclusion of the trial, patients completed a questionnaire regarding pen needle satisfaction.. The 5 mm needle was preferred by 41.8% of study subjects, while the 8 mm needle was preferred by 27.9% of subjects. For other attributes (i.e. overall injection comfort, pain when inserting the needle into the skin and length of needle), the 5 mm needle scored higher than the 8 mm needle and higher also than the percentage of individuals who indicated no preference.. In patients with insulin-treated type 2 diabetes with a mean single-injection volume dose of basal insulin of 50.2 units, the 5 mm needle was generally preferred over the 8 mm needle. The shorter needle was more comfortable and easier to use while being equally effective in delivering insulin.

Topics: Canada; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Injections, Subcutaneous; Insulin; Insulin Detemir; Insulin Glargine; Needles; Patient Preference; Patient Safety; Patient Satisfaction; Surveys and Questionnaires; Treatment Outcome

To investigate the efficacy and tolerability of empagliflozin added to basal insulin-treated type 2 diabetes.. Patients inadequately controlled [glycated haemoglobin (HbA1c) >7 to ≤10% (>53 to ≤86 mmol/mol)] on basal insulin (glargine, detemir, NPH) were randomized to empagliflozin 10 mg (n = 169), empagliflozin 25 mg (n = 155) or placebo (n = 170) for 78 weeks. The baseline characteristics were balanced among the groups [mean HbA1c 8.2% (67 mmol/mol), BMI 32.2 kg/m(2) ]. The basal insulin dose was to remain constant for 18 weeks, then could be adjusted at investigator's discretion. The primary endpoint was change from baseline in HbA1c at week 18. Key secondary endpoints were changes from baseline in HbA1c and insulin dose at week 78.. At week 18, the adjusted mean ± standard error changes from baseline in HbA1c were 0.0 ± 0.1% (-0.1 ± 0.8 mmol/mol) for placebo, compared with -0.6 ± 0.1% (-6.2 ± 0.8 mmol/mol) and -0.7 ± 0.1% (-7.8 ± 0.8 mmol/mol) for empagliflozin 10 and 25 mg, respectively (both p < 0.001). At week 78, empagliflozin 10 and 25 mg significantly reduced HbA1c, insulin dose and weight vs placebo (all p < 0.01), and empagliflozin 10 mg significantly reduced systolic blood pressure vs placebo (p = 0.004). Similar percentages of patients had confirmed hypoglycaemia in all groups (35-36%). Events consistent with urinary tract infection were reported in 9, 15 and 12% of patients on placebo, empagliflozin 10 and 25 mg, and events consistent with genital infection were reported in 2, 8 and 5%, respectively.. Empagliflozin for 78 weeks added to basal insulin improved glycaemic control and reduced weight with a similar risk of hypoglycaemia to placebo.

Topics: Aged; Benzhydryl Compounds; Blood Glucose; Blood Pressure; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Glucosides; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Male; Middle Aged; Treatment Outcome; Urinary Tract Infections; Weight Loss

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

Hyperglucagonemia is a characteristic feature of type 2 diabetes (T2DM) that has been postulated to be due to β-cell dysfunction and the resultant loss of insulin-mediated α-cell suppression. When administered in early T2DM, short-term intensive insulin therapy (IIT) can improve β-cell function, resulting in reduced glycemic variability.. To evaluate the impact of IIT on hyperglucagonemia and its associations with β-cell function and glycemic variability. Design/Setting/Participants/Intervention: Sixty-two patients with T2DM of mean 3.0 ± 2.1 years duration and glycated hemoglobin of 6.8 ± 0.7% underwent 4 weeks of IIT, consisting of basal detemir and premeal insulin aspart.. Glucagon response was measured by area under the glucagon curve (AUCglucagon) on oral glucose tolerance test at baseline and 1 day post-IIT. β-Cell function before and after IIT was assessed by Insulin Secretion-Sensitivity Index-2 and ΔISR0-120/Δglucose0-120*Matsuda index (where ISR is the prehepatic insulin secretion rate determined by C-peptide deconvolution). Glucose variability was assessed in both the first and last weeks by the coefficient of variation of capillary glucose on daily six-point self-monitoring profiles.. Both Insulin Secretion-Sensitivity Index-2 and ΔISR0-120/Δglucose0-120*Matsuda index demonstrated improvement in β-cell function after IIT (both P ≤ .02), accompanied by reduced glycemic variability (P = .05). There was a marked reduction in AUCglucagon after IIT, as compared to baseline (P < .001). However, the decrease in AUCglucagon was not associated with the change in either β-cell measure (both P ≥ .34) or glucose variability (P = .37).. Short-term IIT can reduce post-challenge hyperglucagonemia in early T2DM, but this effect does not appear to be due to improved β-cell function.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glucagon; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin, Long-Acting; Insulin, Regular, Human; Male; Middle Aged; Pancreatic Diseases; Up-Regulation

We performed a non-inferiority trial comparing insulin detemir (Levemir) and biphasic insulin (NovoMix70) to standard care during Ramadan fast in insulin treated type 2 diabetes mellitus (T2DM) patients. This was an open label, controlled, multicentre, cluster randomised non-inferiority study. Insulin treated T2DM patients from 12 randomly selected primary clinics received Levemir and NovoMix 70 (intervention, n = 127) or standard care according to the American Diabetes Association recommendations (control, n = 118). Insulin dose (intervention) was 60% of the usual, of this 40% was dosed as Levemir at sunrise and 60% as NovoMix 70 before dinner. Insulin was titrated according to daily 4 point self-measured blood glucose (4P-SMBG) levels. The primary outcome was the difference in mean daily 4P-SMBG during days 23-30 of treatment. Mean age was 60.1 (SD 8.9) and 59.4 (SD 10.1) years in the intervention and control respectively. Mean HbA1c was 8.38% (68 mmol/mol) (SD 0.96) and 8.45% (69 mmol/mol) (SD 1.08). Mean BMI was 32.99 (SD 7.05) and 33.08 (SD 7.24), respectively. The intervention was non-inferior to standard care as assessed by mean 4P-SMBG during days 23-30 of treatment [155 (SD 30.76) mg% and 159 (SD 33.24) mg% respectively, p = 0.269]. Adverse event rate was significantly lower in the intervention group [0.04 (SD 0.06) vs. 0.07 (SD 0.11), p = 0.010]. In particular, hypoglycaemia event rate was lower in the intervention group [0.00 (SD 0.01) vs. 0.01 (SD 0.03), p ≤ 0.001]. To conclude, treatment with Levemir and NovoMix 70 was non-inferior to standard care in this heterogeneous group of patients and was associated with less adverse events.

Topics: Adult; Aged; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Detemir; Islam; Male; Middle Aged; Prospective Studies; Quality of Life

Weight gain upon insulin initiation is opposite to clinical goals in diabetes management. This trial aimed to determine the impact of modest dietary intervention on weight change and examine weight change in baseline body mass index strata when initiating once-daily insulin detemir (IDet) in overweight or obese insulin-naïve individuals with type 2 diabetes (T2D).. DIET (Impact of Dietary Intervention on Weight Change in Subjects With Type 2 Diabetes) was a 26-week, randomized, treat-to-target, stratified, controlled, open-label, multinational trial. Subjects were randomized 1 : 1 to either the IDet group, which received basic dietary and physical exercise advice at baseline, or the Diet+IDet group, which had additional dietary consultations with a certified dietician (three face-to-face meetings, three phone contacts).. Mean estimated change in body weight from baseline ± standard error (SE) was -1.05 ± 0.23 kg for Diet+IDet and -0.56 ± 0.23 kg for IDet alone. Estimated mean difference was 0.49 kg (95% confidence interval: -0.15; 1.13, p = 0.132). Glycaemic control, measured by haemoglobin A1c (HbA1c) and fasting plasma glucose, improved similarly in both groups. Both groups reported variable reductions in caloric intake and overall physical activity levels. No difference in hypoglycaemia rates between groups was observed.. This study suggests that a modest dietary intervention plus basic lifestyle advice, compared with basic lifestyle advice alone, resulted in similar weight change, efficacy, safety and tolerability when initiating IDet once daily in overweight or obese insulin-naïve individuals with T2D.

Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Directive Counseling; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin, Long-Acting; Male; Obesity; Risk Reduction Behavior; Treatment Outcome; Weight Loss

There are acknowledged benefits to continuing metformin when initiating insulin, but there appears to be growing concern over the role of sulphonylureas and thiazolidinediones when used in combination with insulin. This analysis investigates the effects of continuing or discontinuing oral antidiabetic drugs (OADs) following the initiation of once-daily insulin detemir.. SOLVE is a 24-week, multinational observational study of insulin detemir initiation in patients with type 2 diabetes mellitus treated with one or more OADs.. In the total cohort (n = 17 374), there were significant improvements in HbA1c (-1·3%, 95% CI -1·34; -1·27%) and weight (-0·6 kg, 95% CI -0·65; -0·47 kg), with an increase in the incidence rate of minor hypoglycaemia (+0·256 events ppy, P < 0·001), but not severe hypoglycaemia (-0·038 events ppy, P < 0·001). Study participants had information on OAD use either prior to (n = 17 086) or during insulin initiation (n = 16 346). HbA1c reductions were significantly greater in patients continuing treatment with metformin (-1·3% vs. -1·1%, P < 0·01), thiazolidinediones (-1·3% vs. -1·0%, P < 0·01) and DPP-IV inhibitors (-1·3% vs. -0·9%, P < 0·001). Final insulin doses were significantly greater in patients discontinuing treatment with sulphonylureas (0·29 vs. 0·26 IU/kg, P < 0·001), glinides (0·28 vs. 0·26 IU/kg, P < 0·01), thiazolidinediones (0·31 vs. 0·26 IU/kg, P < 0·001) and DPP-IV inhibitors (0·35 vs. 0·29 IU/kg, P < 0·001) compared with patients continuing these respective agents. All patient subgroups had a mean weight loss irrespective of OAD continuation, apart from those continuing thiazolidinediones (+0·2 kg). The largest improvements in weight were seen following the withdrawal of sulphonylureas and thiazolidinediones (-1·1 and -1·1 kg, respectively).. Discontinuation (or switching) of OADs at the time of insulin initiation appears to be governed principally by concerns about hypoglycaemia and weight. HbA1c improvements were smaller in patients discontinuing OADs at the time of insulin initiation and may be associated with insufficient insulin titration.

Topics: Administration, Oral; Aged; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin, Long-Acting; Male; Metformin; Middle Aged; Prospective Studies; Sulfonylurea Compounds; Thiazolidinediones

Pharmacokinetic and pharmacodynamic profiles of exogenous insulin may be affected by intrinsic factors, such as age, ethnicity/race, and hepatic and renal function. Insulin degludec (IDeg) is a basal insulin with an ultralong duration of action and a flat and stable glucose-lowering effect profile.. The purpose of this study was to investigate whether the pharmacokinetic and pharmacodynamic responses to IDeg at steady state vary according to patient race/ethnicity.. This randomized, single-center, double-blind, 2-period crossover trial investigated responses to IDeg in 59 patients with type 2 diabetes mellitus from 3 groups: African American, Hispanic/Latino, and white. Patients were allocated randomly to a sequence of 2 treatment periods, separated by a 7- to 21-day washout period, with once-daily IDeg or insulin detemir dosing for 6 days at a predefined fixed dose level (0.6 U/kg). Differences in pharmacokinetic and pharmacodynamic variables among groups were analyzed using an ANOVA with treatment period, an interaction between race/ethnicity, and treatment as fixed factors, subject as a random effect, and residual variance, depending on treatment.. Total exposure to IDeg during one dosing interval at steady state (AUCIDeg,τ,SS) was similar among the racial/ethnic groups (ratio [95% CI]: African American vs white, 1.10 [0.91-1.31]; African American vs Hispanic/Latino, 1.13 [0.95-1.34]; and Hispanic/Latino vs white, 0.97 [0.82-1.16]). The total glucose-lowering effect of IDeg (AUCGIR,τ,SS) was also similar among the groups, with no statistically significant difference in pairwise comparisons (1940, 1735, and 2286 mg/kg in African American, white, and Hispanic/Latino patients, respectively). Steady state was reached in all groups after 2 to 3 days of dosing. In all groups, both exposure and glucose-lowering effect for IDeg were evenly distributed between the first and second 12 hours of the 24-hour dosing interval at steady state (mean AUCIDeg,0-12h,SS/AUCIDeg,τ,SS = 53%-54%; AUCGIR,0--12h,SS/AUCGIR,τ,SS = 47%-52%).. The similar pharmacokinetic and pharmacodynamic responses to IDeg in 3 racial/ethnic groups of patients with type 2 diabetes mellitus suggest that the flat, stable, and ultralong pharmacokinetic and pharmacodynamic profiles of IDeg are preserved irrespective of race/ethnicity. Although insulin doses must be adjusted on an individual basis, similar pharmacokinetic and pharmacodynamic responses to IDeg are observed in patients with differing race/ethnicity.

Topics: Adult; Aged; Analysis of Variance; Apathy; Black or African American; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Hispanic or Latino; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin, Long-Acting; Liver; Male; Middle Aged; White People

To compare once- versus twice-daily insulin detemir added on OADS therapy in insulin-naive type 2 diabetes patients in terms of efficacy and safety.. An open-label study performed at a single center, comprised a randomized, crossover 24 week with insulin-naive type 2 diabetes patients. Insulin detemir was initiated with mean 0.12 U/kg in all patients (Group I once-daily, Group II twice-daily) and titrated for 24 week.. A total of 50 patients completed the study (Group I n:25, Group II n:25). With use of once- and twice-daily insulin, HbA1c values were decreased by 1.8% (±2.0) and 1.5% (±1.4) within the first 12 weeks (p<0.01), whereas increased by 0.21% (±0.7) and 0.14% (±0.8) in the second 12 weeks (p>0.05). The increases in the insulin doses were found as 0.22 U/kg and 0.35 U/kg with once- and twice-daily insulin use, respectively (p:0.04). Although minor hypoglycemic events were similar in both groups in the first 12 weeks, 2-fold increase was found in the patients shifting from once- to twice-daily dose. Within the first and second periods, the body weight of the patients was observed an increase of 0.4 and 1.6 kg with once-daily dose, whereas a decrease of 0.1 and 2.1 kg in the twice-daily dose, in the same period.. Once-daily use of insulin detemir up to 0.4 U/kg was found to have similar efficacy and safety as twice-daily use. Twice dose use of insulin did not provide a prominent glycemic control advantage on 1.5-fold higher use of insulin.

Topics: Administration, Oral; Biomarkers; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged; Time Factors; Treatment Outcome; Turkey; Weight Gain

Hemodialyzed patients with diabetes face an increased cardiovascular risk. Optimal glycemic control can reduce morbidity and mortality, but it is difficult to achieve because of the alternation between dialysis and non-dialysis periods. This study evaluated the contribution of continuous glucose monitoring (CGM) to the management of insulin regimen.. In this pilot prospective multicenter study, we performed CGM (Navigator®, Abbott, Rungis, France) for a total of 54 hours at baseline and for a 3-month follow-up period in a group of 28 hemodialyzed patients with type 2 diabetes treated by a basal-bolus detemir plus aspart insulin regimen. Insulin therapy was adapted to the CGM values. HbA1c and CGM parameters collected over the 3-month treatment period were compared using MANOVA for repeated measures.. After 3 months, HbA1c significantly decreased from 8.4 ± 1.0% (65 ± 1 mmol/mol) to 7.6 ± 1.0% (60 ± 11 mmol/mol; p < 0.01). Similarly, mean CGM glucose values significantly decreased from 9.9 ± 1.9 to 8.9 ± 2.1 mmol/L (p = 0.05). The frequency of glucose values > 10 mmol/L significantly decreased from 41.3 ± 21.9% to 30.1 ± 22.4% (p < 0.05), without a significant increase in the frequency of glucose values < 3.3 mmol/L. Insulin requirements significantly increased from 70 ± 51 IU/d to 82 ± 77 IU/d (p < 0.001), without significant changes in body weight.. CGM-adapted insulin regimen improves glycemic control without increasing hypoglycemic events in hemodialyzed diabetic patients. CGM could be a useful tool for the management of insulin therapy in these patients. These results need to be confirmed by long-term studies with larger sample sizes.

Topics: Adolescent; Adult; Aged; Blood Glucose; Blood Glucose Self-Monitoring; Body Weight; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Male; Middle Aged; Monitoring, Ambulatory; Pilot Projects; Prospective Studies; Renal Dialysis; Risk Factors; Young Adult

To compare the efficacy and safety of new insulin glargine 300 units/mL (Gla-300) with glargine 100 units/mL (Gla-100) in people with type 2 diabetes using basal insulin (≥42 units/day) plus oral antihyperglycemic drugs (OADs).. EDITION 2 was a multicenter, open-label, two-arm study. Adults receiving basal insulin plus OADs were randomized to Gla-300 or Gla-100 once daily for 6 months. The primary end point was change in HbA1c. The main secondary end point was percentage of participants with one or more nocturnal confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycemic events from week 9 to month 6.. Randomized participants (n = 811) had a mean (SD) HbA₁c of 8.24% (0.82) and BMI of 34.8 kg/m(2) (6.4). Glycemic control improved similarly with both basal insulins; least squares mean (SD) reduction from baseline was -0.57% (0.09) for Gla-300 and -0.56% (0.09) for Gla-100 (mean difference -0.01% [95% CI -0.14 to 0.12]), with 10% higher dose of Gla-300. Less nocturnal confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycemia was observed with Gla-300 from week 9 to month 6 (relative risk 0.77 [95% CI 0.61-0.99]; P = 0.038) and during the first 8 weeks. Fewer nocturnal and any time (24 h) hypoglycemic events were reported during the entire 6-month period. Weight gain was lower with Gla-300 than with Gla-100 (P = 0.015). No between-treatment differences in safety parameters were identified.. Gla-300 was as effective as Gla-100 and associated with a lower risk of hypoglycemia during the night and at any time of the day.

Topics: Administration, Oral; Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged

This study assessed the efficacy and safety of once-daily insulin initiation using insulin detemir (detemir) or insulin glargine (glargine) added to existing metformin in type 2 diabetes (T2D).. This 26-week, multinational, randomized, treat-to-target trial involved 457 insulin-naïve adults with T2D (HbA1c 7-9%). Detemir or glargine was added to current metformin therapy [any second oral antidiabetic drug (OAD) discontinued] and titrated to a target fasting plasma glucose (FPG) ≤90 mg/dl (≤5.0 mmol/l). Primary efficacy endpoint was change in HbA1c.. Mean (s.d.) HbA1c decreased with detemir and glargine by 0.48 and 0.74%-points, respectively, to 7.48% (0.91%) and 7.13% (0.72%) [estimated between-treatment difference, 0.30 (95% CI: 0.14-0.46)]. Non-inferiority for detemir at the a priori level of 0.4%-points was not established. The proportions of patients reaching HbA1c ≤ 7% at 26 weeks were 38% and 53% (p = 0.026) with detemir and glargine, respectively. FPG decreased ∼43.2 mg/dl (∼2.4 mmol/l) in both groups [non-significant (NS)]. Treatment satisfaction was good for both insulins. Hypoglycaemia, which occurred infrequently, was observed less with detemir than glargine [rate ratio 0.73 (95% CI 0.54-0.98)]. The proportions of patients reaching HbA1c ≤ 7% without hypoglycaemia in the detemir and glargine groups were 32% and 38% (NS), respectively. Weight decreased with detemir [-0.49 (3.3) kg] and increased with glargine [+1.0 (3.1) kg] (95% CI for difference: -2.17 to -0.89 kg).. While both detemir and glargine, when added to metformin therapy, improved glycaemic control, glargine resulted in greater reductions in HbA1c, while detemir demonstrated less weight gain and hypoglycaemia.

Topics: Argentina; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Middle Aged; Patient Satisfaction; Republic of Korea; Thailand; Treatment Outcome; United States

In type 2 diabetes mellitus, treatment with insulin is initiated when HbA1c is reduced inadequately with oral antidiabetic drugs or incretin mimetics. Whether insulin analogues vs. regular human insulin have favorable effects in terms of efficacy and metabolism is under discussion.. 29 patients with type 2 diabetes mellitus (19 males, 10 females) with a mean age 59±11(mean±SD) years (range 24-75) and treated with oral drugs for at least 6 months and a HbA1c >7.0% were included in an open, randomised, prospective, controlled, multicenter parallel-group study over a period of 24 months.. 11 patients were randomized in the regular human insulin-group (RHI-group) and 18 patients in the insulin aspart group (IA-group). Insulin aspart or regular human insulin should be treated to <140 mg/dl postprandial and insulin detemir should be treated to <110 mg/dl in the morning (fasting) after a previous dose titration of insulin aspart or regular human insulin over 6 months of treatment. Adiponectin, HbA1c, fasting plasma glucose, BMI, triglycerides and cholesterol levels were determined every 3 months.. 7/11 of the RHI-group received additional insulin detemir and 13/18 of the IA-group. HbA1c levels decreased significantly in both groups (8.7±1.6 to 7.2±0.9 in the RHI-group (p<0.05) vs. 8.7±1.6 to7.3±0.9 in the IA-group (p<0.05)) without significant difference between the groups. No significant changes were seen between the 2 groups during the 24 months period in terms of BMI, fasting plasma glucose, lipids. Adiponectin serum levels decreased over the time without difference between the groups (7.9±4.0 to 5.0±2.0 in the RHI-group (p<0.03) vs. 7.3±3.4 to 4.8±2.8 in the IA-group (p<0.0001)). During the first 9 months, the insulin dosage to reach the postprandial blood glucose <140 mg/dl, were significantly lower in the IA-group, but approached the following the RHI-group without significant changes after 24 months.. After stopping oral antidiabetic drugs in type 2 diabetes mellitus, insulin aspart in comparison to human regular insulin decreased effectively HbA1c levels without significant difference. Moreover, insulin aspart in comparison to human regular insulin does not have any substantial benefits concerning metabolic effects and adipocytokines in type 2 diabetes mellitus over a 24 months treatment period.

Topics: Adiponectin; Adult; Aged; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Fasting; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Aspart; Insulin Detemir; Insulin, Long-Acting; Lipids; Male; Middle Aged; Prospective Studies; Treatment Outcome

Short-term intensive insulin therapy (IIT) can improve pancreatic β-cell function when administered early in the course of type 2 diabetes mellitus (T2DM). However, the degree of improvement in response to this therapy varies between patients. Thus, we sought to characterize the determinants of improvement in β-cell function in response to short-term IIT in early T2DM. Sixty-three patients with mean 3.0 ± 2.1 yr duration of T2DM and Hb A1c of 6.8 ± 0.8% underwent 4 wk of IIT consisting of basal insulin detemir and premeal insulin aspart, with oral glucose tolerance test administered at baseline and 1 day post-IIT. β-Cell function before and after IIT was assessed by Insulin Secretion Sensitivity Index-2 (ISSI-2). Reversibility of β-cell dysfunction was defined as percentage change in ISSI-2 of ≥25%. Overall, the study population experienced an increase in ISSI-2 from baseline to post-IIT (P = 0.01), with one-third of participants achieving ≥25% improvement in ISSI-2. Compared with their peers, those with increases in ISSI-2 of ≥25% had greater decrements in fasting glucose (P < 0.0001), Hb A1c (P = 0.001), ALT (P = 0.04), AST (P = 0.02), and HOMA-IR (P < 0.0001). On logistical regression analysis, baseline Hb A1c (OR = 2.83, 95% CI 1.16-6.88, P = 0.02) and change in HOMA-IR (OR = 0.008, 95%CI 0.0004-0.16, P = 0.001) emerged as independent predictors of reversibility of β-cell dysfunction. Indeed, reversibility of β-cell dysfunction was achieved in only those participants in whom IIT yielded an improvement in HOMA-IR. In conclusion, decline in HOMA-IR may be a key determinant of improvement of β-cell function in response to short-term IIT, suggesting a fundamental contribution of insulin resistance to the reversible component of β-cell dysfunction in early T2DM.

Topics: Adult; Diabetes Mellitus, Type 2; Disease Progression; Drug Administration Schedule; Female; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin-Secreting Cells; Insulin, Long-Acting; Insulin, Regular, Human; Male; Middle Aged; Prognosis; Treatment Outcome

The pharmacodynamic properties of a single dose of 0.5 U/kg insulin detemir and insulin glargine were compared during two 24-h isoglycaemic clamps, one week apart.. The order of treatments was randomised. At approximately 0830 h, persons with T2DM received subcutaneous administration of a 0.5 U/kg dose of either insulin detemir or insulin glargine into the anterior abdominal wall. Plasma glucose was measured at 10-min intervals throughout the 24-h clamp period and isoglycaemia was maintained by variable infusion of 20% glucose. Glucose infusion rates (GIR) and plasma C-peptide were determined throughout each 24-h period.. Eleven persons with type 2 diabetes (8 male) with mean (SD) age 58.5 years (8.5), BMI 30.8 kg/m² (2.8) and HbA1c 7.5% (0.6) were studied. Plasma glucose remained constant during the clamp (CV: insulin detemir 3.7%; insulin glargine 3.8%). Following injection of insulin detemir, GIR increased, reaching a mean peak of 2.29 mg/kg/min (95% CI 1.64, 2.94) at 11.6h (range 8.9 to 14.3) compared to 1.71 mg/kg/min (95% CI 1.4, 2.0) at 10.2 h (8.1 to 12.3) for insulin glargine (P=0.025 for GIR(max)). Plasma C-peptide decreased during the study period, remaining significantly lower than the fasting level at the study end after both analogues, insulin detemir (P=0.01) and insulin glargine (P=0.02).. In persons with T2DM, no difference in duration of action following a single subcutaneous dose of insulin detemir and insulin glargine could be observed. Insulin detemir showed greater between subject variability and achieved a significantly higher maximum GIR than insulin glargine.

Topics: Adolescent; Adult; Aged; Area Under Curve; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Glucose Clamp Technique; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Young Adult

This multicenter, open-label, parallel-arm study compared the efficacy and safety of exenatide once weekly (EQW) with titrated insulin detemir in patients with type 2 diabetes inadequately controlled with metformin (with or without sulfonylureas).. Patients were randomized to EQW (2 mg) or detemir (once or twice daily, titrated to achieve fasting plasma glucose ≤5.5 mmol/L) for 26 weeks. The primary outcome was proportion of patients achieving A1C ≤7.0% and weight loss ≥1.0 kg at end point, analyzed by means of logistic regression. Secondary outcomes included measures of glycemic control, cardiovascular risk factors, and safety and tolerability.. Of 216 patients (intent-to-treat population), 111 received EQW and 105 received detemir. Overall, 44.1% (95% CI, 34.7-53.9) of EQW-treated patients compared with 11.4% (6.0-19.1) of detemir-treated patients achieved the primary outcome (P < 0.0001). Treatment with EQW resulted in significantly greater reductions than detemir in A1C (least-square mean ± SE, -1.30 ± 0.08% vs. -0.88 ± 0.08%; P < 0.0001) and weight (-2.7 ± 0.3 kg vs. +0.8 ± 0.4 kg; P < 0.0001). Gastrointestinal-related and injection site-related adverse events occurred more frequently with EQW than with detemir. There was no major hypoglycemia in either group. Five (6%) patients in the EQW group and six (7%) patients in the detemir group experienced minor hypoglycemia; only one event occurred without concomitant sulfonylureas (detemir group).. Treatment with EQW resulted in a significantly greater proportion of patients achieving target A1C and weight loss than treatment with detemir, with a low risk of hypoglycemia. These results suggest that EQW is a viable alternative to insulin detemir treatment in patients with type 2 diabetes with inadequate glycemic control using oral antidiabetes drugs.

Topics: Aged; Diabetes Mellitus, Type 2; Exenatide; Female; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin, Long-Acting; Male; Metformin; Middle Aged; Peptides; Sulfonylurea Compounds; Treatment Outcome; Venoms

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 newly diagnosed type 2 diabetes mellitus (T2DM) patients, short-term insulin therapy might improve β-cell function and glycemic control. This study aimed to compare the effects of basal insulin monotherapy with continuous subcutaneous insulin infusion (CSII) treatment.. Fifty-nine cases of newly diagnosed T2DM patients with fasting plasma glucose of 9.0-16.7 mmol/L were recruited into this study. They were hospitalized and randomly assigned to a basal insulin monotherapy group (n=27) or a CSII group (n=32). Insulin dosage was titrated according to fasting capillary blood glucose levels, and treatment was stopped after 2 weeks. Intravenous glucose tolerance tests were performed, and blood glucose, insulin, C-peptide, and lipid profiles were measured before therapy and 2 days after therapy withdrawal.. Both treatments reduced fasting and postprandial blood glucose levels (after treatment vs. baseline, both P<0.05). Fasting glycemic control target was achieved in 52 cases (88.14%) with 2 weeks of insulin treatment, and there were no significant differences between the glargine and CSII groups (P=0.059). The time to achieve fasting glycemic target in the CSII group was shorter than that in the glargine group (P<0.01). Plasma lipid profiles such as triglycerides and total cholesterol also decreased significantly after the intervention. Overall β-cell function improved significantly after insulin intervention (P<0.01). Variation did not differ between two groups, nor did the effects on insulin and C-peptide secretion (P>0.05).. The effect of basal insulin monotherapy was similar to that of CSII, and thus basal insulin monotherapy might be a reasonable alternative to CSII for initial insulin therapy in newly diagnosed T2DM patients.

Topics: Blood Glucose; China; Diabetes Mellitus, Type 2; Female; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Infusions, Subcutaneous; Insulin Detemir; Insulin Infusion Systems; Insulin, Long-Acting; Male; Middle Aged; Postprandial Period; Treatment Outcome

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

Conventionally, biphasic human insulin (30/70, BHI) is used twice daily for the management of patients with diabetes. However, this regimen is suboptimal to control post-lunch and/or pre-dinner hyperglycaemia in some patients. This study was undertaken to compare the efficacy and safety of thrice-daily biphasic human insulin (30/70, BHI) versus basal detemir and bolus aspart (BB) in patients with poorly controlled type 2 diabetes mellitus (T2DM).. In this open labelled randomized pilot study, 50 patients with uncontrolled T2DM on twice-daily BHI and insulin sensitizers were randomized either to BHI thrice-daily or BB regimen. HbA1c, six point plasma glucose profile, increment in insulin dose, weight gain, hypoglycaemic episodes and cost were compared between the two treatment groups at the end of 12 wk.. Mean HbA l c (± SD) decreased from 9.0 ± 0.9 per cent at randomization to 7.9 ± 0.8 per cent in BHI (P<0.001) and from 9.4 ± 1.3 to 8.2 ± 1.0 per cent in BB regimen (P<0.001) after 12 wk of treatment. The mean (± SEM) weight gain in patients in the BHI regimen was 1.5 ± 0.33 kg compared to 1.4 ± 0.34 kg in the BB regimen. Insulin dose increment at 12 wk was significantly more in the BB regimen 0.46 ± 0.32 U/kg/day compared to 0.15 ± 0.21 U/kg/day in the BHI regimen (P<0.001). The incidence of major as well as minor hypoglycaemic episodes was not different in both the regimen. The BB regimen was more expensive than the BHI regimen (P<0.001).. The thrice daily biphasic human insulin regimen is non-inferior to the basal bolus insulin analogue regimen in terms efficacy and safety in patients with poorly controlled T2DM. However, these data require further substantiation in large long term prospective studies.

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

Chronic diabetic complications result from an imbalance between vascular damage and regeneration. Several circulating lineage-committed progenitor cells have been implicated, but no data are available on pericyte progenitor cells (PPCs). Based on the evidence that PPCs increase in cancer patients after chemotherapy, we explored whether circulating PPC levels are affected by glucose control in type 2 diabetic patients, in relation to the presence of chronic complications. We enumerated peripheral blood PPCs as Syto16+CD45-CD31-CD140b+ events by flow cytometry at baseline and after 3 and 6 months of glucose control by means of add-on basal insulin therapy on top of oral agents in 38 poorly controlled type 2 diabetic patients. We found that, in patients with microangiopathy (n = 23), the level of circulating PPCs increased about 2 fold after 3 months and then returned to baseline at 6 months. In patients without microangiopathy (control group, n = 15), PPCs remained fairly stable during the whole study period. No relationship was found between change in PPCs and macroangiopathy (either peripheral, coronary, or cerebrovascular). We conclude that glucose control transiently mobilizes PPCs diabetic patients with microangiopathy. Increase in PPCs may represent a vasoregenerative event or may be a consequence of ameliorated glucose control on microvascular lesions.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Flow Cytometry; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Middle Aged; Pericytes; Stem Cells; Treatment Outcome

The aim of this study was to report outcomes using detemir and a protocol aimed at intensive blood glucose control with home monitoring in diabetic cats, and to compare the results with a previous study using the same protocol with glargine. Eighteen cats diagnosed with diabetes and previously treated with other insulins were included in the study. Data was provided by owners who joined the online German Diabetes-Katzen Forum. The overall remission rate was 67%. For cats that began the protocol before or after 6 months of diagnosis, remission rates were 81% and 42%, respectively (P = 0.14). No significant differences were identified between the outcomes for the glargine and detemir studies, with the exception of three possibly interrelated factors: a slightly older median age of the detemir cohort at diabetes diagnosis, a higher rate of chronic renal disease in the detemir cohort and lower maximal dose for insulin detemir.

Topics: Animals; Blood Glucose Self-Monitoring; Cat Diseases; Cats; Cohort Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Treatment Outcome

We evaluated the addition of liraglutide to metformin in type 2 diabetes followed by intensification with basal insulin (detemir) if glycated hemoglobin (A1C) ≥7%.. In 988 participants from North America and Europe uncontrolled on metformin ± sulfonylurea, sulfonylurea was discontinued and liraglutide 1.8 mg/day added for 12 weeks (run-in). Subsequently, those with A1C ≥7% were randomized 1:1 to 26 weeks' open-label addition of insulin detemir to metformin + liraglutide (n = 162) or continuation without insulin detemir (n = 161). Patients achieving A1C <7% continued unchanged treatment (observational arm). The primary end point was A1C change between randomized groups.. Of 821 participants completing the run-in, 61% (n = 498) achieved A1C <7% (mean change -1.3% from 7.7% at start), whereas 39% (n = 323) did not (-0.6% from 8.3% at start). During run-in, 167 of 988 (17%) withdrew; 46% of these due to gastrointestinal adverse events. At week 26, A1C decreased further, by 0.5% (from 7.6% at randomization) with insulin detemir (n = 162) versus 0.02% increase without insulin detemir (n = 157) to 7.1 and 7.5%, respectively (estimated treatment difference -0.52 [95% CI -0.68 to -0.36]; P < 0.0001). Forty-three percent of participants with insulin detemir versus 17% without reached A1C <7%. Mean weight decreased by 3.5 kg during run-in, then by 0.16 kg with insulin detemir or 0.95 kg without insulin detemir. In the randomized phase, no major hypoglycemia occurred and minor hypoglycemia rates were 0.286 and 0.029 events per participant-year with and without insulin detemir (9.2 vs. 1.3%).. Supplementation of metformin with liraglutide and then insulin detemir was well tolerated in the majority of patients, with good glycemic control, sustained weight loss, and very low hypoglycemia rates.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Diabetes Mellitus, Type 2; Female; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin, Long-Acting; Liraglutide; Male; Metformin; Middle Aged

Hypoglycemic risk and improved glycemic control have to be weightened when a decision on intensification of treatment of type 2 diabetes mellitus with basal insulin is made. Findings from randomized studies are available in this respect, and should be complemented by data from routine treatment.. The international, prospective, open-label, observational study SOLVE (Study of Once-Daily Levemir) investigated add-on treatment with basal insulin in type 2 diabetes mellitus using once daily insulin detemir in patients currently receiving oral antidiabetic drugs (OAD). Data were collected between initiation of insulin treatment and the final visit after approximately 24 weeks. The primary objective of the study was to evaluate the incidence of serious adverse drug reactions (SADR), including major hypoglycemic events.. In Germany, 2,090 patients were eligible for the full analysis set and 1,671 patients for the effectiveness analysis set. The mean age was 64.9 years, mean duration of diabetes 9.36 years, and mean duration of OAD treatment 7.29 years. Three patients (0.14%) experienced a SADR (1 fall resulting in death, 2 major hypoglycemic events). At the final visit, there was a significant reduction in major hypoglycemic events if compared with the period before starting insulin treatment (0.002 versus 0.120 events per patient year, p < 0.001), as were minor hypoglycemic events (0.880 versus 1.588 events per patient year, p = 0.006). The mean body weight and BMI decreased by -0.9 kg (p < 0.001) and-0.35 kg/m2 (p < 0.001) respectively and the mean HbA(1c) level improved from 8.45 +/- 1.19% to 7.30 +/- 0.92% (-1.15 +/- 1.08%; p < 0.001). The mean fasting plasma glucose level and plasma glucose variability were significantly reduced.. Baseline data of the study underline the need for earlier intensification of antidiabetic therapy in type 2 diabetes in Germany. Study results show that within the German diabetes care system, initiation of basal insulin therapy with insulin detemir is able to result in significant HbA(1c) improvements without increased risk of hypoglycemia and/or weight gain.

Topics: Adult; Aged; Aged, 80 and over; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged; Prospective Studies

The aim of this trial was to evaluate the efficacy and safety of the combination of once-daily insulin detemir (IDet) and sitagliptin (SITA) versus SITA ± sulphonylurea (SU), both in combination with metformin (MET) in insulin-naive subjects.. In a 26-week, open-label, randomized, parallel-group study in type 2 diabetes, insulin-naive subjects concomitantly treated with MET ± second oral antidiabetic drug (OAD) were randomized 1 : 1 to IDet + SITA + MET or SITA + MET ± SU. All continued with MET treatment, and those treated with SU continued if randomized to SITA + MET ± SU. Efficacy endpoints included glycosylated haemoglobin (HbA1c), fasting plasma glucose (FPG), 9-point self-measured plasma glucose (SMPG), weight, body mass index (BMI). Safety endpoints included adverse events (AEs) and hypoglycaemia.. Significantly higher reductions in HbA1c, FPG and SMPG were achieved with IDet + SITA + MET compared with SITA + MET ± SU. Estimated HbA1c decreased by 1.44% in the IDet + SITA + MET group versus 0.89% in SITA + MET ± SU, p < 0.001. FPG decreased by 3.7 mmol/l (66.3 mg/dl) versus 1.2 mmol/l (22.2 mg/dl), p < 0.001, respectively. Small decreases in weight and BMI were observed in both arms, with no significant differences. AEs were mild or moderate and were more common in the SITA + MET ± SU arm than in the IDet + SITA + MET arm. There was no major hypoglycaemia. Observed rates of hypoglycaemia were very low (1.3/1.7 episodes/patient year) in both arms. The subgroup treated with MET and SUs prior to the trial achieved similar results.. The combination of once-daily IDet with SITA showed a clinically and significantly better improvement in glycaemic control than SITA in combination with or without SUs. Both regimens were associated with a low rate of hypoglycaemia and slight weight reduction.

Topics: Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Male; Metformin; Middle Aged; Pyrazines; Sitagliptin Phosphate; Treatment Outcome; Triazoles; Weight Loss

In diabetes, endothelial damage promotes macroangiopathy and endothelial regeneration is impaired, owing to reduced endothelial progenitor cells (EPCs). Given that insulin influences endothelial biology, we compared the effects of add-on basal insulin analogues on endothelial damage and regeneration in type 2 diabetes (T2D).. This was a 6-month randomized crossover trial comparing add-on insulin detemir versus glargine in poorly controlled T2D with macroangiopathy. At baseline, crossover (3 months) and study end (6 months), we measured HbA1c, EPCs, circulating endothelial cells (CECs), VCAM-1, ICAM-1 and E-selectin. Body weight and hypoglycaemic episodes were also recorded.. Forty-two patients completed the study, randomly assigned to the glargine-detemir (n = 21) or the detemir-glargine (n = 21) schedule. At crossover, EPC levels did not change compared with baseline, but significantly increased at study end. CECs decreased over time and were significantly reduced at study end. ICAM-1, VCAM-1 and E-selectin were significantly reduced at crossover and further decreased at study end. No differences were seen in these effects between detemir and glargine. HbA1c showed a carryover effect and its reduction was similar with detemir and glargine in the first arm. Incidence of hypoglycaemia and weight gain was lower with detemir than with glargine in both arms.. Optimized glycaemic control by add-on basal insulin improved indexes of endothelial damage and regeneration. Compared to glargine, detemir achieved similar endothelial protection with lower weight gain and less hypoglycaemia. These results might have implications for therapy of aging T2D patients with cardiovascular disease.

Topics: Aged; Cross-Over Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Dose-Response Relationship, Drug; Drug Administration Schedule; Endothelial Cells; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Treatment Outcome

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

Trial research has predominantly focused on patient and staff understandings of trial concepts and/or motivations for taking part, rather than why treatment recommendations may or may not be followed during trial delivery. This study sought to understand why there was limited attainment of the glycaemic target (HbA(1c) ≤6.5%) among patients who participated in the Treating to Target in Type 2 Diabetes Trial (4-T). The objective was to inform interpretation of trial outcomes and provide recommendations for future trial delivery.. In-depth interviews were conducted with 45 patients and 21 health professionals recruited from 11 of 58 trial centres in the UK. Patients were broadly representative of those in the main trial in terms of treatment allocation, demographics and glycaemic control. Both physicians and research nurses were interviewed.. Most patients were committed to taking insulin as recommended by 4-T staff. To avoid hypoglycaemia, patients occasionally altered or skipped insulin doses, normally in consultation with staff. Patients were usually unaware of the trial's glycaemic target. Positive staff feedback could lead patients to believe they had been 'successful' trial participants even when their HbA(1c) exceeded 6.5%. While some staff felt that the 4-T automated insulin dose adjustment algorithm had increased their confidence to prescribe larger insulin doses than in routine clinical practice, all described situations where they had not followed its recommendations. Staff regarded the application of a 'one size fits all' glycaemic target during the trial as contradicting routine clinical practice where they would tailor treatments to individuals. Staff also expressed concerns that 'tight' glycaemic control might impose an unacceptably high risk of hypoglycaemia, thus compromising trust and safety, especially amongst older patients. To address these concerns, staff tended to adapt the trial protocol to align it with their clinical practices and experiences.. To understand trial findings, foster attainment of endpoints, and promote protocol fidelity, it may be necessary to look beyond individual patient characteristics and experiences. Specifically, the context of trial delivery, the impact of staff involvement, and the difficulties staff may encounter in balancing competing 'clinical' and 'research' roles and responsibilities may need to be considered and addressed.

Topics: Aged; Attitude of Health Personnel; Biomarkers; Clinical Protocols; Diabetes Mellitus, Type 2; Drug Dosage Calculations; Female; Glycated Hemoglobin; Guideline Adherence; Health Knowledge, Attitudes, Practice; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin, Long-Acting; Male; Medication Adherence; Middle Aged; Practice Guidelines as Topic; Qualitative Research; Research Design; Treatment Outcome; United Kingdom

We examined the impact of an aspart insulin protocol for treatment of hyperglycemia in the emergency department (ED) coupled with rapid initiation of a detemir-aspart insulin protocol for patients admitted to the hospital.. ED patients with type 2 diabetes mellitus and a blood glucose (BG) ≥ 200 mg/dL were randomized to intervention (INT) or usual care (UC). INT patients (n = 87) received aspart every 2 hours when BG > 200 mg/dL, and if admitted, began daily detemir in the ED. UC patients (n = 89) were treated per hospital physicians.. The initial ED BG was 304 ± 76 mg/dL. The final ED BG differed: 217 ± 71 mg/dL for INT patients versus 257 ± 89 mg/dL for UC patients (P < .01). No INT patients and 3 UC patients had a BG < 50 mg/dL (P = .5). ED length of stay (LOS) was similar: 5.4 ± 1.8 hours for INT patients versus 4.9 ± 1.9 hours for UC patients (P = .06). Sixty-nine percent from each group were admitted. Admission BG was 184 ± 74 mg/dL for INT patients versus 224 ± 93 mg/dL for UC patients (P < .01). Patient-day weighted mean glucose was 163 ± 39 mg/dL for INT patients versus 202 ± 39 mg/dL for UC patients (P < .01). One INT patient and 6 UC patients had a BG < 50 mg/dL (P = .11). Hospital LOS was similar: 2.7 ± 2.0 versus 3.1 ± 1.9 days, respectively (P = .58).. An aspart insulin protocol safely lowers BG levels in the ED without prolonging LOS. During hospitalization, a detemir-aspart protocol achieves significantly better glycemic control compared with guideline-driven use of NPH-aspart or glargine/detemir-aspart (usual care) without increasing hypoglycemia. Standardization of insulin protocols in the ED and hospital settings leads to improvement in overall glycemic control with greater safety and efficacy than usual care.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Emergency Medical Services; Emergency Service, Hospital; Female; Hospitalization; Humans; Hyperglycemia; Insulin Aspart; Insulin Detemir; Insulin, Long-Acting; Length of Stay; Male; Middle Aged; Treatment Outcome

Sporadic reports on immediate and delayed cutaneous reactions to insulin detemir, a modern insulin analogue, have raised unsupported claims of allergy of type I, III and IV. The purpose of this experimental study using a provocative design was to elucidate the potential mechanisms behind such skin reactions.. A total of 40 patients with type 1 diabetes or insulin-requiring type 2 diabetes, all naïve to insulin detemir, were injected on the thigh with 0.l mL of insulin detemir (Levemir(®)) administered with an 8 mm needle at three different depths, i.e. intradermal, subdermal and subcutaneously. Saline was injected as control. Any cutaneous reactions were assessed after 10 and 30 min, after 24 and 48 h and after 7 days. Histopathology of positive reactions on day 7 was obtained. The study was randomized, controlled, double-blinded, and conducted in accordance with ICH-GCP guidelines. Blood flow was recorded with the Periflux PF5010, and skin colour (a*) with the DSMII colorimeter.. Clinical reading, flowmetry and colorimetry consistently showed delayed reactions after intradermal insulin injection (35 of 40 patients reacted with mainly weak reactions, P<0.05), peaking after 48 h, contrasting no special reaction immediately after injection, except for reactions attributed to needle trauma. A total of 22 patients reacted on subdermal injection and 21 on subcutaneous injection. Histopathology on day 7 from 22 reactions in 15 patients showed a consistent pattern of inflammation with eosinophilia as typically observed in adverse skin reactions to a variety of medicines. Reactions were interpreted as non-specific biologic responses to the insulin different from direct toxic actions and classical allergic reaction patterns. Only one person registered itch/discomfort. A prick test vs. histamine reference excluded insulin detemir to be a pharmacological histamine releaser. Thus, provocative testing with insulin detemir produced delayed skin reaction but no immediate reaction. Measurement of circulating insulin detemir-specific antibodies by RIA before and after 3 months showed no increase.. Non-allergic delayed skin reactions from intradermal and, to a minor degree, subdermal and subcutaneous injections of insulin detemir were frequent in this experimental study and showed a consistent histology pattern of inflammation with eosinophilia. Immediate reactions were not produced. The reactions are unlikely to be specific for insulin detemir, and other insulins should be studied in a similar provocative design.

Topics: Adult; Antibodies; Colorimetry; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Eruptions; Female; Histamine; Humans; Hypersensitivity, Delayed; Hypersensitivity, Immediate; Hypoglycemic Agents; Injections, Intradermal; Insulin Detemir; Insulin, Long-Acting; Laser-Doppler Flowmetry; Male; Middle Aged; Skin

To determine whether an insulin algorithm could be used in a similar manner in the setting of diabetes and stress hyperglycaemia following cessation of intravenous (IV) insulin after cardiac surgery.. Subjects who were clinically stable, requiring ≥ 1 unit/h of IV insulin 48 h after surgery, were randomized to once daily detemir at 50, 65 or 80% of IV insulin requirements and received aspart according to carbohydrate intake. Diabetes was defined as any history of diabetes or preoperative HbA1c 6.5%.. The morning glucose in patients with diabetes was 143 mg/dl (n = 61) vs. 124 mg/dl in those with stress hyperglycaemia (n = 21,p = 0.05) on day 1 and 127 vs. 110 mg/dl over 72 h (p = 0.01). This was unaffected by adjustment for initial dosing group. At 72 h, 56% of patients with stress hyperglycaemia reached AM (80-130 mg/dl) and 87% reached overall (80-180 mg/dl) glucose targets, compared to 90 and 100% of patients with stress hyperglycaemia, respectively. There was no difference in hypoglycaemia in patients with stress hyperglycaemia or diabetes. The percentage of patients with diabetes receiving insulin was 46% on admission and 77% at discharge, compared to 0 and 42% of patients with stress hyperglycaemia.. Following cardiac surgery, patients with stress hyperglycaemia may be converted from IV insulin to detemir with a 50% conversion factor, while patients with diabetes may require a higher conversion factor. Stress hyperglycaemia may be prolonged; the intensity and duration of insulin therapy required for optimal outcomes warrants further examination.

Topics: Algorithms; Body Mass Index; Cardiac Surgical Procedures; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; Infusions, Intravenous; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged; Postoperative Period; Stress, Physiological; Treatment Outcome

PREDICTIVE (Predictable Results and Experience in Diabetes through Intensification and Control to Target: an International Variability Evaluation) is a large, multinational, open-label, prospective, observational study addressed to assess the efficacy and safety of insulin detemir in clinical practice. This paper reports 26 weeks of follow-up data, from 1298 type 2 diabetes patients from Italy.. In this observational study, the primary end point was the incidence of serious adverse drug reactions (SADRs), including major hypoglycemia. Secondary end points were: hemoglobin A1c (HbA1c), mean self-monitored fasting glucose, within-patient fasting glucose variability and body weight change.. Insulin detemir significantly improved glycemic control, with a decrease in mean HbA1c, fasting glucose and within-patient fasting glucose variability. Interestingly, the improvements in glycemic control occurred in association with a small, but significant reduction in weight. The safety results of this study showed that 26 weeks of treatment with insulin detemir was associated with a very low rate of SADRs (only 14 events), which mainly consisted of hypoglycemia (78%, of which 42% were major hypoglycemia).. Insulin detemir improves glycemic control, with low risk of hypoglycemia, no weight gain and an excellent safety profile; these data support the overall findings of PREDICTIVE.

Topics: Adult; Aged; Blood Glucose Self-Monitoring; Body Weight; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin, Long-Acting; Italy; Male; Middle Aged; Young Adult

The aim of this study was to evaluate the weight change from baseline while using insulin detemir in subjects with type 2 diabetes mellitus under normal clinical practice conditions. It was a multicentre, open label, non-randomised, non-interventional, observational, safety and efficacy study in subjects using insulin detemir for the treatment of type 2 diabetes mellitus. In this study, the mean body weight decreased marginally by -0.8 kg at the end of week 26 from baseline. Change in mean body weight during the study was not statistically significant (p > 0.05). There was a statistically significant (p < -0.05) change in waist circumference (-0.7 cm) from baseline at week 26. Mean fasting plasma glucose reduced significantly (p < 0.0001) from 199.1 mg/dl at initiation of insulin detemir to 141.3 mg/dl at week 13 and 115.8 mg/dl at week 26. Mean HbA1c reduced significantly (p < 0.0001) from 9.2% at initiation of insulin detemir to 7.8% at week 13 and 7.2% at week 26. Insulin dose changed marginally from the baseline (15.1 units) to week 26 (15.3 units). Majority of the subjects (89%) were on once daily insulin detemir. Before initiating insulin detemir proportion of subjects experiencing at least one episode of hypoglycaemia during the past four weeks was 8.8% (n = 884). It was reduced 2.4% (n = 241) at week 13 and 1.6% (n = 164) at week 26 following initiation of insulin detemir. There were no major nocturnal hypoglycaemic episodes during 26 weeks of insulin detemir therapy. In conclusion, this study indicates that insulin detemir is safe, effective and weight neutral.

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

The efficacy of either detemir or glargine is comparable in subjects with type 2 diabetes when combined with insulin aspart in a basal-bolus regimen. Subjects randomized to detemir used slightly higher daily insulin doses, but gained less weight on average than glargine-treated subjects.

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

In a previous publication we reported no difference in the 24-hour glucose response between two basal analog insulins, detemir and glargine, when taken once a day in type 2 diabetes mellitus (T2DM). We now report the dose comparison observed within this randomized, double-blind, crossover study.. Of 36 patients on basal insulin and other noninsulin treatments, 29 completed the study. Both insulins were given once a day at 8 pm and no food was taken between 6 pm and the following morning. The dose was titrated daily by continuous glucose monitoring (CGM) until the basal glucose (between 12 and 6 am) was <120 mg/dl but not >5% of CGM readings <70 mg/dl. Subjects were then crossed over to the other insulin and titrated similarly.. Glucose goals were achieved in all subjects. The mean dosage was 0.26 U/kg with very few subjects requiring >0.4 U/kg. Only 2 required an absolute dose less than 10 U/day and all others required more, some considerably higher. Of the 29 subjects, 7 required a greater, 6 a smaller, and 16 the same dose of detemir compared to glargine.. When given once daily in T2DM and titrated using CGM to the same fasting glucose, there was no difference in the glucose response between basal insulins during the basal titration period (4-10 hours after injection) nor during the entire 24-hour period following the injection. Further, the mean dosage to achieve this glucose goal was the same with both insulins.

Topics: Aged; Blood Glucose Self-Monitoring; Cross-Over Studies; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Middle Aged; Monitoring, Ambulatory

To determine whether glargine is noninferior to detemir regarding the percentage of patients reaching A1C <7% without symptomatic hypoglycemia

Topics: Administration, Oral; Diabetes Mellitus, Type 2; Drug Administration Schedule; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Treatment Outcome; Weight Gain

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

Insulin lispro protamine suspension (ILPS) and insulin detemir were compared in insulin-naive patients with Type 2 diabetes poorly controlled by oral glucose-lowering agents (OGLAs) to demonstrate non-inferior overall glycaemic control.. This was a 24-week, multinational, open-label, parallel-group, treat-to-target trial. Adults taking two or more OGLAs were randomized to ILPS (n = 223) or detemir (n = 219) once daily at bedtime. Doses were titrated to target fasting blood glucose (FBG) 5.0-7.2 mmol/l. A pre-breakfast dose was added up to week 8 per prespecified criteria. The primary objective was comparison of glycated haemoglobin (HbA(1c)) change from baseline (non-inferiority margin 0.4%).. At end-point, HbA(1c) decreased from 8.8 +/- 0.7% in both groups to 7.3 +/- 0.9% (ILPS) and 7.5 +/- 1.1% (detemir). Least-squares mean difference (95% confidence interval) for HbA(1c) [-0.21% (-0.39, -0.03)] and glycaemic variability [0.10 mmol/l (-0.02, 0.23)] demonstrated non-inferiority. End-point mean FBG was 7.0 vs. 6.9 mmol/l (P = 0.85), and percentages of patients achieving H < 7.0% were 34.9% vs. 31.2% for ILPS vs. detemir. More ILPS patients used twice-daily dosing (59% vs. 49%). Mean daily insulin dose was 0.39 vs. 0.46 U/kg (P = 0.005) and weight gain was 1.88 vs. 0.36 kg (P < 0.001) for ILPS vs. detemir. Overall hypoglycaemia (episodes patient(-1) year(-1)) (24.2 +/- 33.0 vs. 16.2 +/- 26.1, P = 0.001) and nocturnal (6.3 +/- 12.1 vs. 3.8 +/- 13.2, P < 0.001) rates were higher for ILPS.. At end-point, ILPS was non-inferior to detemir in HbA(1c) change from baseline. Patients using ILPS achieved lower end-point HbA(1c) with lower insulin doses but greater hypoglycaemia and weight gain.

Topics: Aged; Body Weight; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Lispro; Insulin, Long-Acting; Male; 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

Costs for diabetes treatment burden statutory health care systems. Aim of the LIVE-COM study (Long Acting Insulin Glargine versus Insulin Detemir Cost Evaluation Comparison) was to assess resource utilization and costs of diabetes care as well as patient reported outcomes in a random sample of type 2 diabetes patients treated with either insulin glargine (GLA) or detemir (DET) as part of a basal-bolus regimen in a primary care setting.. LIVE-COM is a non-interventional, cross-sectional study performed between April and September 2008 in 138 randomly selected centers of primary care physicians in Germany. From 1731 type 2 diabetes patients (GLA: n = 1150; DET: n = 581) with statutory health insurance status and pretreatment with either GLA or DET for at least 6 months as part of a basal-bolus therapy, total direct costs of diabetes care (for insulins, oral antidiabetic drugs, test strips, needles, lancets, Hypokits®) were calculated from total recorded expenditures, for a period of six months, from the perspective of statutory health insurance. Patient-reported outcomes were assessed using validated questionnaires (SF-12, DTSQs, ITEQ).. Mean total costs per patient over six months were lower with GLA based therapy compared with DET based therapy (972 euro ± 374 euro vs. 1135 euro ± 477 euro, p < 0.001). Adjusted by ANCOVA: 932 euro (95% CI: 905, 957 euro) vs. 1.061 euro (95% CI: 1025, 1099 euro, p < 0.001). The adjusted mean single costs for basal insulin (223 euro vs. 246 euro), bolus insulin (241 euro vs. 289 euro), test strips (347 euro vs. 393 euro) and needles (67 euro vs. 80 euro) were significantly lower in the GLA group (p < 0.001, each), whereas costs of OAD (36 euro vs. 35 euro), lancets (14 euro vs. 15 euro) and Hypokits® (1.9 euro vs. 1.0 euro) did not differ significantly. Glycemic parameters (HbA1c, fasting blood glucose) were better on GLA based therapy (p < 0.01) and associated with lower daily total insulin doses (68 U vs. 79 U). Furthermore, slightly better results in patient-reported outcomes were found in GLA patients.. In a head-to-head comparison over six months a glargine vs. detemir based basal-bolus therapy in type 2 diabetes patients was associated with lower total costs of diabetes care Δ: -128 euro/patient) mainly caused by savings of consumables. Further health services research with larger sample sizes should be conducted to obtain a more comprehensive analysis of economic aspects of insulin analogs or other innovative drugs in routine practice.

Topics: Aged; Ambulatory Care; Cost-Benefit Analysis; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Germany; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; National Health Programs; Patient Satisfaction; Primary Health Care

Topics: Administration, Oral; Adult; Aged; Cost Savings; Diabetes Mellitus, Type 2; Drug Costs; Drug Therapy, Combination; Female; Germany; Health Care Costs; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; National Health Programs

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

Once-daily dosing with insulin detemir and insulin glargine were compared in a double-blind, randomised, crossover study in type 2 diabetes subjects previously treated with other antihyperglycaemic medications. Blood glucose was measured through continuous glucose monitoring (CGM). Insulin dose was adjusted daily during the titration phase to achieve target blood glucose values of (70-120 mg/dL) during the basal period, defined as 2400-0600 hours. The last meal of the day started at 1800 h and basal insulin was injected at 2000 h. The CGM data for a 24-h period on the second consecutive day after achieving target blood glucose levels were compared between treatments. Twenty-nine subjects completed the study. Over a 24-h measurement period, once-daily dosing with insulin detemir provided glycaemic control very similar to that of once-daily insulin glargine in patients with type 2 diabetes after both had been titrated to the same glucose target. Insulin detemir- and insulin glargine-treated subjects had similar mean 24-h glucose values (133 +/- 21 mg/dL compared with 126+/-20 mg/dL respectively, p = 0.385) and similar glucose values during the basal period (105 +/- 23 mg/dL compared with 98 +/- 19 mg/dL, respectively p = 0.204).Target basal glycaemic control was achieved in all subjects in a mean of 3.8 days for detemir and 3.5 days for glargine (p = 0.360). The mean dose of detemir was similar to that of glargine (26.3 and 26.6 units/day, respectively, p = 0.837). In this study, once-daily dosing of insulin detemir provided 24-h glycaemic control similar to that of insulin glargine in patients with type 2 diabetes.

Topics: Adult; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Glucose Clamp Technique; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome; Young Adult

The aim of this study was to compare a simplified patient-driven algorithm (303 Algorithm) to physician-driven adjustments in a subset of 193 patients with type 2 diabetes from the PREDICTIVE 303 study who were using basal-bolus insulin therapy.. PREDICTIVE 303 was a 26-week, randomized, phase 4 study, in which subjects were either instructed to adjust their insulin detemir dose every 3 days by +/-3 units if mean fasting plasma glucose (FPG) values were above 110 mg/dL or below 80 mg/dL (303 Algorithm), or had physicians adjust the insulin detemir dose according to usual practice (Standard-of-care).. Patients in both groups achieved similar reductions in glycated hemoglobin (-0.2% and -0.3% for 303 Algorithm and Standard-of care groups, respectively; between groups P=0.60). 303 Algorithm group patients achieved a greater reduction in FPG (-21.3 mg/dL vs. 0.2 mg/dL; between groups P=0.03). Both 303 Algorithm and Standard-of care groups experienced a similar rate of overall hypoglycemia, and similar weight reduction (-1.7 kg and -0.4 kg, respectively; between groups P=0.07). Over 82% of patients in both groups used insulin detemir once daily.. Adjustments of a once-daily detemir dose by patients using the 303 Algorithm in a basal-bolus setting is equally effective in improving glycemic control in patients with type 2 diabetes compared with physician-directed basal dose adjustments.

Topics: Aged; Algorithms; Blood Glucose; Blood Glucose Self-Monitoring; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Monitoring; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Detemir; Insulin, Long-Acting; Linear Models; Male; Middle Aged; Physician's Role; Practice Guidelines as Topic; Safety; Self Administration; Treatment Outcome; United States

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

The aim was to compare clinical outcomes by different dosing frequencies of insulin detemir (detemir) used over 52 weeks in various regimens.. This analysis involved French patients enrolled in PREDICTIVE (a large-scale, multinational, observational study of empirical use of detemir in everyday clinical practice) for whom data have been collected over 52 weeks. Three cohorts were considered: patients with type 1 diabetes; patients with type 2 diabetes using detemir in a basal insulin plus oral antidiabetic drug (OAD) regimen; patients with type 2 diabetes using detemir as part of basal-bolus insulin therapy. In each cohort, data were stratified according to detemir dosing frequency at the beginning and end of 52 weeks: once daily (o.d.) at the beginning and end; twice daily (b.i.d.) at the beginning and end; o.d. at the beginning, but b.i.d. at the end. Endpoints assessed included glycated hemoglobin, fasting plasma glucose, hypoglycemia, weight, and insulin dose.. There were improvements in glycemic control and tolerability in all subgroups. Patients completing on o.d. dosing tended to have better outcomes than those completing on b.i.d. dosing in all cohorts, and o.d. administration was associated with lower insulin dosing. There was little evidence that switching from o.d. to b.i.d. dosing influenced outcomes other than insulin dose. However, there were some baseline differences between subgroups selected for o.d. and b.i.d. dosing that might have influenced outcomes: many patients appeared to have been continued on previous basal dosing frequencies; for others, b.i.d. detemir dosing seemed to be used to intensify previous therapy.. With the caveat that empirical choices of dose frequency were made, this analysis shows that empirical use of o.d. detemir produces results at least as good as empirical use of b.i.d. detemir in basal-bolus-treated type 1 and type 2 diabetes, and in basal plus OAD-treated type 2 diabetes.

Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged; Prospective Studies; Treatment Outcome

To compare efficacy and safety of two fasting plasma glucose (FPG) titration targets [4.4-6.1 mmol/l (80-110 mg/dl) and 3.9-5.0 mmol/l (70-90 mg/dl)] using a patient-directed, treat-to-target algorithm for once-daily basal insulin in insulin-naïve subjects with type 2 diabetes suboptimally treated with oral antidiabetes drugs (OADs).. In this 20-week, randomized, controlled, open-label, multicentre, treat-to-target study, 244 insulin-naïve subjects with type 2 diabetes, HbA(1c)>or=7.0 and

Topics: Algorithms; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged; Patient Participation; Treatment Outcome

This treat-to-target study compared the efficacy and safety of insulin detemir (IDet) and insulin glargine (IGla) in a basal-bolus (insulin aspart) regimen in type 2 diabetes.. 385 patients were randomized 2 : 1 (IDet : IGla). Non-inferiority of IDet to IGla was determined by HbA(1c) 95% CI upper limit <0.4.. IDet and IGla showed similar efficacy in HbA(1c) reduction at 26 weeks, as the non-inferiority criterion was met at 26 weeks (LS mean [Det-Gla]: 0.207; 95% CI: 0.0149,0.3995). It appeared that IGla in some cases did better than IDet in terms of HbA(1c), but the difference (0.207%) was not clinically meaningful. Based on the CONSORT guideline, non-inferiority analysis using the LOCF approach was inconclusive regarding possible inferiority of delta 0.4 (LS mean of [Det-Gla]: 0.307; 95% CI: 0.1023, 0.5109). HbA(1c) decreased significantly from baseline in IDet (-1.1% [26 weeks], -0.9% [LOCF], p < 0.001) and in IGla (-1.3% [26 weeks, LOCF], p < 0.001). Final HbA(1c) were 7.1% (26 weeks) and 7.3% (LOCF) in IDet, and 6.9% (26 weeks) and 7.0% (LOCF) in IGla. Final FPG were 130 mg/dL (26 weeks) and 135 mg/dL (LOCF) in IDet, and 134 mg/dL (26 weeks) and 137 mg/dL (LOCF) in IGla. There was significantly less weight gain in IDet-treated patients (1.2 +/- 3.96 kg versus 2.7 +/- 3.94 kg, p = 0.001). Hypoglycemia risk was comparable between groups. The majority of IDet-treated patients (87.4%) remained on a once-daily basal insulin regimen throughout the study.. IDet and IGla were both effective and safe treatments for glycemic control in a basal-bolus regimen for type 2 diabetes. Clinically significant reductions in HbA(1c) were achieved in both groups, but with significantly less weight gain in the IDet group at comparable basal insulin dosage.

Topics: Adult; Blood Glucose; Body Mass Index; Confidence Intervals; Diabetes Mellitus, Type 2; Edema; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Poisson Distribution; Respiratory Tract Infections; Time Factors; Treatment Outcome; Weight Gain

The primary aim was to evaluate duration of action of a single 0.8 U/kg dose of insulin lispro protamine suspension (ILPS) in type 2 diabetes (T2DM) patients; secondarily to compare onset and duration of action of ILPS, glargine (G), and detemir (D) (0.8 U/kg) and evaluate pharmacokinetic (PK) and pharmacodynamic (PD) dose responses of ILPS.. In a single-center, double-blind, five-arm crossover study, 34 patients were randomized to a treatment sequence which included a single subcutaneous 0.8 U/kg dose of G and D and three doses of ILPS (0.4 U/kg, 0.8 U/kg, and 1.2 U/kg) and were studied using 24-hour euglycemic glucose clamps.. Duration of action was determined as the time to the last measurable glucose infusion rate (tR(last)) during glucose clamps.. The duration of insulin action (tR(last)) for ILPS at 0.8 U/kg was >23 hours and was similar to G (p = 0.114) and D (p = 0.570). Post-hoc analysis demonstrated the probability of achieving 24 hours of glucose-lowering activity after a 0.8 U/kg dose: 48% (ILPS), 43% (G), and 26% (D). G(tot) and R(max) were significantly greater for ILPS versus G or D. The median ILPS time-dependent values demonstrated a significantly earlier maximum PD response (tR(max) and early 50% tR(max)) versus either G or D. ILPS demonstrated dose-dependent increases in PK and PD measures across the dose range.. Following a single 0.8 U/kg dose in T2DM patients, ILPS, G, and D demonstrated similar durations of glucose-lowering activity and ILPS demonstrated significantly greater glucose-lowering activity (R(max) and G(tot)) and earlier maximum PD response. These results potentially support once-daily dosing of ILPS in T2DM.. The observed number of 24-hour censored observations was higher than expected and the wash-out period for basal insulin treated patients may have been too short to definitively rule out a carry-over effect; however, such an effect, if present, would potentially only affect onset of action and not the primary outcome measure.

Topics: Adult; Aged; Cross-Over Studies; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Male; Middle Aged; Protamines; Suspensions

The intuitiveness, instruction time, and handling of the Levemir (insulin detemir) FlexPen and the Lantus OptiClik pen (with insulin glargine) were investigated.. This randomized open-label crossover study involved two groups of insulin-device-naive Japanese patients with type 2 diabetes [mean (SD) age 61.9 +/- 12.3 years, 57% male]. Patients were evaluated on the ease-of-use of each insulin pen without instruction [intuitiveness group (n = 32)], or with instruction [instruction time group (n = 29)]. Patient preferences for the respective devices were assessed by questionnaire.. FlexPen required significantly less instruction time (p < .001) and was objectively more intuitive to use (p < .001) than OptiClik. Nevertheless, few patients in the intuitiveness group felt confident injecting either pen prior to instruction (FlexPen, 31%; OptiClik, 16%). No patients in the instruction time group found FlexPen difficult to learn, whereas 45% of patients found OptiClik difficult or very difficult to learn. FlexPen was rated simpler to use (77% versus 12%; p < .001), easier to inject (67% versus 13%; p < .001), and more convenient (71% versus 12%; p < .001) compared with OptiClik. More patients would trust FlexPen to deliver insulin injections (p < .01) and would prefer to use FlexPen compared with OptiClik (82% versus 13%; p < .001).. FlexPen was faster to teach, simpler to use, and more trusted by patients compared with OptiClik. Mean injection time was significantly shorter for FlexPen than OptiClik, with or without instruction. This study highlights not only how easy it is for patients to learn to use FlexPen, but also how easily health care providers can teach patients to use it.

Topics: Aged; Asian People; Cross-Over Studies; Diabetes Mellitus, Type 2; Female; Humans; Injections, Subcutaneous; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Patient Education as Topic; Patient Preference

The PREDICTIVE project was an international multicentric, open observation study evaluating the safety and efficiency of insulin detemir in clinical practice. 1,695 type 1 or 2 diabetes mellitus (DM) patients were enrolled in the study in the Czech Republic. The patients were treated by insulin detemir for the period of 26 weeks in accordance with the standard scheme implemented by the treating doctor. The primary objective of the study was to monitor the incidence of serious adverse events including severe hypoglycaemias. The secondary objective of the study (the number of adverse events, the incidence of all and nocturnal hypoglycaemic episodes, the variability of fasting glycaemia, the change in HbA1c at the end of the study, the change in the patients' weight) focused on the safety and efficiency of diabetes treatment.. Insulin detemir therapy resulted in a statistically significant decrease in all nocturnal episodes (from 26.8 to 10.4 episodes/patient/year in type 1 DM; from 9.2 to 2.6 in persons with type 2 DM), in severe nocturnal episodes (from 2.5 to 0.1 episode/patient/year in type 1 DM, and from 0.6 to 0 in type 2 DM), and also in hypoglycaemic nocturnal episodes (from 7.2 to 1.8 episode/patient/year in type 1 DM and from 1.7 to 0.3 in type 2 DM) as compared with the period preceding the therapy. In addition, detemir therapy resulted in a statistically significant improvement of diabetes compensation characterised by a decrease in the average HbAlc from 7.6% to 6.7% in type 1 DM patients, and from 7.9% to 7.0% in type 2 DM patients. Average fasting glycaemia recorded a significant decrease by 2.4 mmol/l in type 1 DM patients, and by 2.3 mmol/l in type 2 DM patients. Also the variability of fasting glycaemia recorded a significant decrease at the end of the study in both patient groups. No major change in weight was recorded in the course of the study in persons with type 1 DM, while a significant decrease in weight was recorded for type 2 DM patients.. The results of the study PREDICTIVE confirmed the data from randomised studies on the safety and efficiency of insulin detemir treatment in the conditions of standard clinical practice in the Czech Republic.

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged

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

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

This trial compared the efficacy and safety profiles of the insulin analogues detemir and glargine as the basal insulin component of a basal-bolus regimen in patients with type 2 diabetes mellitus (T2DM) who were being treated with oral antidiabetic drugs (OADs) or insulin with or without OADs.. This was a multinational, 52-week, openlabel, parallel-group, noninferiority, treat-to-target trial. Patients with a diagnosis of T2DM for > or = 12 months who had been receiving an OAD or insulin, with or without OADs, for > 4 months were randomized in a 2:1 ratio to receive detemir or glargine. According to the approved labeling, detemir could be administered once or twice daily, and glargine was administered once daily. Insulin aspart was given at mealtimes. Insulin secretagogues and a-glucosidase inhibitors were discontinued at study entry, and existing OADs were continued. Doses of detemir and glargine were titrated to achieve a prebreakfast (and predinner for detemir administered twice daily) plasma glucose target of < or = 6.0 mmol/L. Patients monitored their plasma glucose levels before breakfast and dinner on the 3 days before each of 13 scheduled visits, recorded their insulin doses on 1 of these 3 days, and recorded their 10-point self-monitored plasma glucose (SMPG) at baseline and after 24 and 52 weeks. The primary efficacy end point was glycosylated hemoglobin (HbA(1c)) at 52 weeks; secondary efficacy end points included changes in fasting plasma glucose (FPG), postprandial plasma glucose, insulin doses, and weight change at 52 weeks. Safety end points included the frequency of hypoglycemia and adverse events (AEs).. The intention-to-treat population included 319 patients (58.0% male, 42.0% female; 78.4% white; mean age, 58 years; mean weight, 92.8 kg; mean duration of diabetes, 13.6 years). At study entry, 46.1% of patients were receiving insulin and > or = 1 OAD, 35.4 were receiving insulin only, and 18.5% were receiving > or = 1 OAD only. At 52 weeks, there was no significant difference between detemir and glargine in terms of mean HbA(1c) (7.19% and 7.03%, respectively; mean difference, 0.17% [95% CI, -0.07 to 0.40]) or the mean decrease in HbAlc from baseline (-1.52% and -1.68%). The reduction in HbA(1c) was not significantly affected by whether detemir was administered once or twice daily. There were no significant differences between groups in terms of mean FPG (7.05 and 6.68 mmol/L) or the mean change in FPG from baseline (-2.56 and -2.92 mmol/L; mean difference, 0.36; 95% CI, -0.26 to 0.99). The overall shape of the 10-point SMPG profiles was not significantly different between groups. Mean weight gain at 52 weeks was significantly lower with detemir than with glargine (2.8 vs 3.8 kg; mean difference, -1.04; 95% CI, -2.08 to -0.01; P < 0.05). Doses of basal and prandial insulins at the end of the study were not significantly different between groups. Major hypoglycemic episodes were reported by 4.7% and 5.7% of patients in the respective treatment groups. There was no significant difference in the risk of hypoglycemia between groups. The proportion of patients with AEs and the number of AEs per patient were comparable between groups (185/214 patients [86.4%] reporting 743 AEs and 88/105 patients [83.8%] reporting 377 AEs).. when used as indicated as part of a basal-bolus regimen in patients with T2DM who had previously received other insulin and/or OAD regimens, detemir was noninferior to glargine in its effects on overall glycemic control. Both basal insulins were associated with clinically relevant reductions in hyperglycemia. Both were well tolerated, with no significant difference in the frequency of hypoglycemia or AEs.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; International Cooperation; Male; Middle Aged; Patients; Postprandial Period; Time Factors; Treatment Outcome

PREDICTIVE 303 was a 26-week, prospective, randomized, open-label, multi-center study in patients with type 2 diabetes that investigated whether patient-driven adjustments of insulin detemir doses using the 303 Algorithm achieved similar glycemic control compared to standard-of-care, physician-driven adjustments in doses. This post hoc sub-analysis evaluates insulin naïve patients on oral anti-diabetic drugs (OADs) who were directed to start on once-daily insulin detemir as add-on therapy to any other glucose-lowering regimens.. Patients in the 303 Algorithm group were instructed to adjust their detemir dose every 3 days based on mean fasting plasma glucose (FPG) values using a simple algorithm: mean FPG < 80 mg/dL, reduce dose by 3 units; between 80-110mg/dL, no change; > 110mg/dL, increase by 3 units. Physicians adjusted the detemir dose for patients in the Standard-of-care group according to their usual practice. No control insulin was used for comparison to insulin detemir.. Reductions in glycosylated hemoglobin (HbA(1c)) from baseline were similar between those patients in the 303 Algorithm and Standard-of-care groups (-1.1 and -1.0%, respectively; between group p = 0.0933); patients in the 303 Algorithm group achieved a greater reduction in FPG. Patients in both groups experienced a similar, low rate of hypoglycemia. Over 95% and 92% of patients, respectively, used detemir once daily.. These data indicate that patients with type 2 diabetes naïve to insulin can effectively implement the 303 Algorithm to initiate and adjust a once-daily dose of insulin detemir to achieve improvements in glycemic control.

Topics: Aged; Algorithms; Blood Glucose; Body Weight; Circadian Rhythm; Diabetes Mellitus, Type 2; Drug Dosage Calculations; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged; United States

This 52-week multinational, randomised, open-label, parallel-group, non-inferiority trial compared clinical outcomes following supplementation of oral glucose-lowering drugs with basal insulin analogues detemir and glargine in type 2 diabetic patients.. Insulin-naive adults (n=582, HbA(1c) 7.5-10.0%, BMI 7.0 mmol/l after achieving FPG <7.0 mmol/l. Due to labelling restrictions, no second glargine dose was allowed.. Baseline HbA(1c) decreased from 8.6 to 7.2 and 7.1% (NS) with detemir and glargine, respectively. FPG improved from 10.8 to 7.1 and 7.0 mmol/l (NS), respectively. With detemir, 45% of participants completed the study on once daily dosing and 55% on twice daily dosing, with no difference in HbA(1c). Overall, 52% of participants achieved HbA(1c)

Topics: Aged; Blood Glucose Self-Monitoring; Body Mass Index; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged

Weight gain during insulin therapy can be a challenging problem in already overweight type 2 diabetes mellitus patients, affecting treatment compliance and long-term prognosis. The analogue insulin detemir has been reported to have a weight-sparing effect compared with other basal insulins. This pooled analysis investigated whether this potential advantage is related to body mass index (BMI) when insulin detemir is used as the basal component of basal-bolus therapy.. Data were pooled from two randomised, parallel group trials of 22 and 24 weeks' duration, in which 900 insulin-treated patients with type 2 diabetes mellitus had their treatment intensified to basal-bolus therapy. Patients received once- or twice-daily insulin detemir or neutral protamine Hagedorn (NPH) insulin in conjunction with insulin aspart or human soluble insulin at meal times.. Patients treated with insulin detemir had minimal weight gain (mean <1 kg), regardless of their BMI at entry (estimated slope -0.032), whereas, in patients treated with NPH insulin, weight gain increased as baseline BMI increased (estimated slope 0.075, p = 0.025). Indeed, NPH insulin-treated patients with the largest BMI (>35 kg/m(2)) gained the most weight (mean of ~2.4 kg). In contrast, insulin detemir-treated patients with a BMI >35 kg/m(2) lost weight (mean of ~ -0.5 kg). Glycaemic control was similar with the two treatments.. Insulin detemir may provide a clinical advantage in terms of reduced weight gain in the treatment of overweight patients with type 2 diabetes.

Topics: Aged; Body Mass Index; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Humans; Insulin; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged; Weight Gain

This study compared the time-action profiles of the novel albumin-bound basal insulin analogue NN344 with those of insulin detemir and insulin glargine in individuals with type 2 diabetes.. Twenty-seven insulin-treated men with type 2 diabetes [body mass index 30.8 +/- 2.6 kg/m(2) (mean +/- s.d.), haemoglobin A(1c) 7.6 +/- 1.1%] were enrolled in this randomized, double-blind trial and participated in six euglycaemic glucose clamp experiments [target blood glucose (BG) 5 mmol/l] each. Participants received NN344 in three experiments at a dose of 0.8, 1.6 and 2.8 dosing units (DU) (1 DU corresponds to 6 nmol NN344) per kilogram of body weight. In the other three experiments, the participants received 0.4, 0.8 and 1.4 U/kg of either insulin detemir or insulin glargine. The insulin preparations were characterized with regards to their effects on glucose infusion rates (GIRs) (in particular duration of action and within-subject and between-subject variabilities), BG, C-peptide, free fatty acids (FFA), endogenous glucose production (EGP) and peripheral glucose uptake (PGU) over 24 h post-dose.. The mean GIR profiles for all three preparations were similar in shape/flatness and showed increasing effect (area under the curve for GIR: AUC-GIR(total)) with increasing dose [low dose: 647 +/- 580, 882 +/- 634, 571 +/- 647 mg/kg (insulin detemir vs. NN344 vs. insulin glargine]; medium dose: 1203 +/- 816, 1720 +/- 1109, 1393 +/- 1203 mg/kg and high dose: 2171 +/- 1344, 3119 +/- 1549, 2952 +/- 2028 mg/kg; p = 0.48]. The duration of action increased with rising doses of all insulin preparations, without major differences between treatments. BG remained below 7 mmol/l in nearly all the experiments. Within-subject variability was lower for the albumin-bound insulin analogues, insulin detemir and NN344, than for insulin glargine (p < 0.0001). Between-subject variability did not differ between treatments, nor did the effects on BG, C-peptide, FFA, EGP or PGU.. In individuals with type 2 diabetes, the time-action profiles and the duration of action of the albumin-bound insulin analogues, insulin detemir and NN344, were comparable with those of insulin glargine, whereas within-subject variability in the metabolic effect was significantly lower. Therefore, insulin detemir and NN344 seem to be as well suited as insulin glargine for once-daily administration in type 2 diabetes. The better predictability may be an important characteristic of the albumin-bound analogues as insulin detemir has already been shown to improve hypoglycaemia.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Fatty Acids, Nonesterified; Glucose; Glucose Clamp Technique; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged

Adding insulin to oral therapy in type 2 diabetes mellitus is customary when glycemic control is suboptimal, though evidence supporting specific insulin regimens is limited.. In an open-label, controlled, multicenter trial, we randomly assigned 708 patients with a suboptimal glycated hemoglobin level (7.0 to 10.0%) who were receiving maximally tolerated doses of metformin and sulfonylurea to receive biphasic insulin aspart twice daily, prandial insulin aspart three times daily, or basal insulin detemir once daily (twice if required). Outcome measures at 1 year were the mean glycated hemoglobin level, the proportion of patients with a glycated hemoglobin level of 6.5% or less, the rate of hypoglycemia, and weight gain.. At 1 year, mean glycated hemoglobin levels were similar in the biphasic group (7.3%) and the prandial group (7.2%) (P=0.08) but higher in the basal group (7.6%, P<0.001 for both comparisons). The respective proportions of patients with a glycated hemoglobin level of 6.5% or less were 17.0%, 23.9%, and 8.1%; respective mean numbers of hypoglycemic events per patient per year were 5.7, 12.0, and 2.3; and respective mean weight gains were 4.7 kg, 5.7 kg, and 1.9 kg. Rates of adverse events were similar among the three groups.. A single analogue-insulin formulation added to metformin and sulfonylurea resulted in a glycated hemoglobin level of 6.5% or less in a minority of patients at 1 year. The addition of biphasic or prandial insulin aspart reduced levels more than the addition of basal insulin detemir but was associated with greater risks of hypoglycemia and weight gain. (Current Controlled Trials number, ISRCTN51125379 [controlled-trials.com].).

Topics: Administration, Oral; Aged; Blood Glucose; Data Interpretation, Statistical; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin, Long-Acting; Metformin; Middle Aged; Probability; Sulfonylurea Compounds; Treatment Outcome; Weight Gain

The Predictable Results and Experience in Diabetes through Intensification and Control to Target: An International Variability Evaluation 303 (PREDICTIVE 303) Study (n = 5604) evaluated the effectiveness of insulin detemir, a long-acting basal insulin analogue, using a simplified patient self-adjusted dosing algorithm (303 Algorithm group) compared with standard-of-care physician-driven adjustments (Standard-of-care group) in a predominantly primary care setting, over a period of 6 months. Insulin detemir was to be started once-daily as add-on therapy to any other glucose-lowering regimens or as a replacement of prestudy basal insulin in patients with type 2 diabetes. Investigator sites rather than individual patients were randomized to either the 303 Algorithm group or the Standard-of-care group. Patients from the 303 Algorithm group sites were instructed to adjust their insulin detemir dose every 3 days based on the mean of three 'adjusted' fasting plasma glucose (aFPG) values (capillary blood glucose calibrated to equivalent plasma glucose values) using a simple algorithm: mean aFPG < 80 mg/dl (<4.4 mmol/l), reduce dose by 3 U; aFPG between 80 and 110 mg/dl (4.4-6.1 mmol/l), no change; and aFPG > 110 mg/dl (>1.1 mmol/l), increase dose by 3 U. The insulin detemir dose for patients in the Standard-of-care group was adjusted by the investigator according to the standard of care. Mean A1C decreased from 8.5% at baseline to 7.9% at 26 weeks for the 303 Algorithm group and from 8.5 to 8.0% for the Standard-of-care group (p = 0.0106 for difference in A1C reduction between the two groups). Mean FPG values decreased from 175 mg/dl (9.7 mmol/l) at baseline to 141 mg/dl (7.8 mmol/l) for the 303 Algorithm group and decreased from 174 mg/dl (9.7 mmol/l) to 152 mg/dl (8.4 mmol/l) for the Standard-of-care group (p < 0.0001 for difference in FPG reduction between the two groups). Mean body weight remained the same at 26 weeks in both groups (change from baseline 0.1 and -0.2 kg for the 303 Algorithm group and the Standard-of-care group respectively). At 26 weeks, 91% of the patients in the 303 Algorithm group and 85% of the patients in the Standard-of-care group remained on once-daily insulin detemir administration. The rates of overall hypoglycaemia (events/patient/year) decreased significantly from baseline in both groups [from 9.05 to 6.44 for the 303 Algorithm group (p = 0.0039) and from 9.53 to 4.95 for the Standard-of-care group (p < 0.0001)]. Major hypoglycaemi

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome

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

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

This trial compared the efficacy and safety of basal-bolus therapy using either the soluble basal insulin analogue insulin detemir (IDet) in combination with meal-time rapid-acting analogue insulin aspart (IAsp), or NPH insulin (NPH) in combination with meal-time regular human insulin (HSI). This was a 22-week, multinational, open-labelled, symmetrically randomised, parallel group trial including 395 people with type 2 diabetes (IDet + IAsp: 195, NPH + HSI: 200). At 22 weeks, HbA1c was comparable between treatments (IDet + IAsp: 7.46%, NPH + HSI: 7.52%, P = 0.515) with decreases from baseline of 0.65% and 0.58%, respectively. Treatment with IDet + IAsp was associated with a significantly lower within-person variation in self-measured fasting plasma glucose (FPG) (SD:1.20 versus 1.54 mmol/L, p < 0.001), as well as a lower body weight gain (0.51 versus 1.13 kg, p = 0.038) than with NPH + HSI. The risk of nocturnal hypoglycaemia was 38% lower with IDet + IAsp than with NPH + HSI, but statistical significance was not attained (P = 0.14). The overall safety profile was similar between the two treatments. Basal-bolus treatment with IDet + IAsp is an effective and well tolerated insulin regimen in people with type 2 diabetes, resulting in glycaemic control comparable to that of NPH + HSI, but with the advantages of less weight gain and a lower day-to-day within-person variation in FPG.

Topics: Adult; Aged; Blood Glucose; Body Weight; Circadian Rhythm; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Therapy, Combination; Fasting; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin, Long-Acting; Male

Insulin remains a mainstay of treating hyperglycemia in an acute setting. Insulin glargine 300 units/mL (Toujeo, iGlar300) has a different pharmacokinetic profile than 100 units/mL basal insulins, such as insulin detemir (iDet100) and iGlar100. While conversion from iGlar300 to iGlar100 requires a 20% dose decrease, there is currently no recommended interchange from iGlar300 to iDet100.. Compare the incidence of hypoglycemia in patients who received a 1:1 unit interchange from home iGlar300 or iGlar100 to iDet100 while admitted.. A retrospective study was conducted to evaluate adults within a multi-site network admitted between May and December 2019. Patients were included if they received at least one dose of iDet100 following interchange from home iGlar300 or iGlar100. The primary endpoint was the incidence of hypoglycemic events following a 1:1 interchange of iGlar300 vs. iGlar100 to inpatient iDet100. Secondary outcomes include overall hypoglycemic events, time to hypoglycemia, and doses given before hypoglycemia.. Of 615 patients, 394 received a 1:1 unit interchange to iDet100 (52 from iGlar300 and 342 from iGlar100). Incidence of hypoglycemic events was significantly higher in those with a 1:1 interchange from iGlar300 versus iGlar100 (36.5% vs. 18.7%, p = 0.007). Significant differences were observed in overall hypoglycemic events, time to hypoglycemia, and number of doses given before hypoglycemic event.. A 1:1 unit interchange from iGlar300 to iDet100 led to a higher incidence of hypoglycemic events compared to those interchanged from iGlar100. Dose reduction should be considered when transitioning from home iGlar300 to iDet100 in the inpatient setting.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Inpatients; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Retrospective Studies

This study evaluated the use of detemir for treating diabetic dogs with comorbidities that were poorly controlled with intermediate-acting insulins.. 7 insulin-treated diabetic dogs.. Retrospective pilot study. Dogs were treated with detemir for at least 3 months, and glycemia was assessed by the owners at home initially 2 to 4 times daily for 6 to 8 weeks and twice daily thereafter. Clinical evaluations occurred on days 7 to 14, day 30, and then every 60 to 90 days, and dosage adjustments of detemir occurred as needed to control glycemia.. The mean, peak, nadir, morning, and evening preinsulin daily blood glucose concentrations were significantly lower after dosing with detemir for 1, 3, or 6 months and during the last month of treatment compared to the final month of treatment with intermediate-acting insulin. Intermediate-acting insulins resulted in significantly worse glycemic control than detemir in all 3 categories of control. The odds of a biochemical hypoglycemic measurement with detemir were not significantly different compared to intermediate-acting insulins. Clinical hypoglycemia did not occur following detemir treatment. When insulin was withheld because of low morning preinsulin blood glucose concentration < 6.7 mmol/L (≤ 120 mg/dL) and dogs were fed, mean blood glucose concentration was significantly higher 1 hour later. Glucose concentrations were also significantly higher 12 hours later on days when insulin was withheld in the morning or evening for either 1 or 12 hours.. Detemir is useful in diabetic dogs with other comorbidities and can be considered an alternative treatment in poorly controlled diabetic dogs.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Type 2; Dog Diseases; Dogs; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Pilot Projects; Retrospective Studies

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 aimed to compare the rate of hypoglycemic events from all spontaneously reported adverse events (AEs) between insulin detemir and insulin degludec using the Korea Adverse Event Reporting System (KAERS) database.. We analyzed data on the reported hypoglycemia events retrieved from adverse drug reactions (ADR) on the use of different insulin types from 2016 to 2017 in the Korea Institute of Drug Safety & Risk Management-Korea Adverse Event Reporting System Database (KIDS-KD). After defining hypoglycemic events as the AE of interest, we performed a disproportionality analysis by calculating the reporting odds ratio (ROR) to identify the disproportionality of AEs following treatment with insulin degludec (IDeg) and insulin detemir (IDet). Because spontaneously reported hypoglycemic events were not distinguished between insulin glargine 100 U/mL (Gla-100) and insulin glargine 300 U/mL (Gla-300) due to same ATC code by KIDS-KD, direct comparisons of Gla-100 and Gla-300 or comparisons of each analog of insulin glargine vs. IDet or IDeg, respectively, could not be achieved.. Of the 3,220 AEs caused by the use of long-acting basal insulin, 739 and 296 were caused by IDeg and IDet, respectively. Among these, 172 (23.3%) of the 739 and 83 (28.0%) of the 296 AEs were reported to be hypoglycemic events caused by IDeg and IDet, respectively. The rate of reported hypoglycemic events caused by IDeg was lower than that of IDet (ROR (95% CI): 0.78 (0.71 - 0.86)). Further, IDeg consistently caused lower hypoglycemia events than IDet in the sensitivity analysis (ROR (95% CI): 0.41 (0.37 - 0.46)).. When we compared the proportionality of hypoglycemic events among the total number of reported AEs for each of the two basal insulins through disproportionality analysis using the spontaneous ADR reporting system, IDeg showed a relatively lower rate of reported hypoglycemic events than IDet.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Republic of Korea

In comparative randomized studies, use of insulin detemir has been consistently demonstrated to be associated with less weight gain than the industry standard, insulin glargine. However, the magnitude of the relative reduction in weight gain with use of insulin determir vs insulin glargine in regulatory studies (reported values ranged from 0.77 kg to 3.6 kg) may not be generalizable to patients in real-world practice conditions. A study was conducted to substantiate detemir's purported weight-sparing advantage over insulin glargine in newly treated patients with type 2 diabetes mellitus under the conditions found in a clinical practice setting.. A retrospective longitudinal cohort study design was applied in reviewing electronic medical records to identify insulin-naive, overweight patients with type 2 diabetes who received insulin detemir or insulin glargine therapy continued for up to 1 year. Patient weights at baseline and at each subsequent clinic visit after treatment initiation were identified. The primary outcome was the maximum weight increase from baseline after exposure to insulin detemir or glargine. The difference-in-differences (DiD) mean total body weight change was tested by analysis of covariance (ANCOVA).. One hundred nine patient records (56 of patients who received insulin glargine and 53 of patients who received insulin detemir) met study criteria and underwent full abstraction. The covariate-adjusted estimated mean change in body weight associated with use of insulin detemir vs insulin glargine was -1.5 kg (95% CI, -2.89 to -0.12 kg; P = 0.04).. The mean weight gain associated with detemir use was significantly less than the mean weight change observed with glargine use. The magnitude of weight change was consistent with that demonstrated in randomized controlled trials. These results further substantiate detemir's purported comparative weight-sparing properties under conditions found in a real-world practice setting.

Topics: Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Longitudinal Studies; Retrospective Studies; Weight Gain

We aimed to compare the (1) clinical outcomes including composite cardiovascular outcomes, cardiovascular death, and all-cause death, and (2) healthcare costs of using liraglutide and basal insulin as an initial treatment for patients with type 2 diabetes mellitus (T2DM) and high cardiovascular diseases (CVD) risk. This is a retrospective cohort study using Taiwan's Health and Welfare Database. A total of 1057 patients treated with liraglutide were identified and matched with 4600 patients treated with basal insulin. The liraglutide group had a lower risk of a composite CVD outcome (hazard ratio (HR) 0.65; 95% confidence interval (CI) 0.50-0.85; p < 0.01), all-cause mortality (HR 0.40; 95% CI 0.28-0.59; p < 0.0001), and nonfatal stroke (HR 0.54; 95% CI 0.34-0.87; p = 0.01). Compared to the basal insulin group, the liraglutide group had lower median per-patient-per-month (PPPM) inpatient, emergency room (ER), and total medical costs, but higher median PPPM outpatient, total pharmacy, and total costs (all p < 0.0001). In conclusion, compared to basal insulin, liraglutide was found to be associated with reduced risk of a composite CVD outcome, nonfatal stroke, and all-cause mortality among high CVD risk patients with T2DM. In addition, liraglutide users had lower inpatient, ER, and total medical costs, but they had higher outpatient and total pharmacy costs.

Topics: Aged; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Health Care Costs; Humans; Insulin Detemir; Liraglutide; Male; Middle Aged; Retrospective Studies; Risk Factors; Taiwan

Topics: Antibodies, Monoclonal, Humanized; Benzhydryl Compounds; Candida glabrata; Candidiasis, Invasive; Dermatologic Agents; Diabetes Mellitus, Type 2; Female; Glucosides; Humans; Hypoglycemic Agents; Insulin Detemir; Liraglutide; Middle Aged; Psoriasis; Pyelonephritis; Recurrence; Sepsis; Sodium-Glucose Transporter 2 Inhibitors; Urinary Tract Infections

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

The cardiovascular outcomes of insulin detemir in patients with type 2 diabetes mellitus (T2DM) after acute coronary syndrome (ACS) or acute ischemic stroke (AIS) are unclear. The aim of our real-life cohort study was to evaluate the cardiovascular outcomes of insulin detemir (IDet) versus insulin glargine (IGlar) in T2DM patients after ACS or AIS.. A retrospective cohort study was conducted between June 1, 2005, and December 31, 2013, utilizing the Taiwan National Health Insurance Research Database. A total of 3,129 ACS or AIS patients were eligible for the analysis. Clinical outcomes were evaluated by comparing 1,043 subjects receiving IDet with 2,086 propensity score-matched subjects who received IGlar. The primary composite outcome included cardiovascular (CV) death, nonfatal myocardial infarction (MI) and nonfatal stroke.. The primary composite outcome occurred in 322 patients (30.9%) in the IDet group and 604 patients (29.0%) in the IGlar group (hazard ratio [HR], 1.12; 95% confidence interval [CI], 0.95 to 1.32) with a mean follow-up of 2.4 years. No significant differences were observed for CV death (HR, 1.09; 95% CI, 0.86 to 1.38), nonfatal MI (HR, 0.88; 95% CI, 0.66 to 1.19), and nonfatal stroke (HR, 1.15; 95% CI, 0.97 to 1.35). There were similar risks of all-cause mortality, hospitalization for heart failure and revascularization between the IDet group and the IGlar group (P = .647, .115, and .390 respectively).. Compared with IGlar, in T2DM patients after ACS or AIS, IDet was not associated with increased risks of CV death, nonfatal MI, or nonfatal stroke.. ACS = acute coronary syndrome; AIS = acute ischemic stroke; ASCVD = atherosclerotic cardiovascular disease; CI = confidence interval; CV = cardiovascular; DKA = diabetic ketoacidosis; HHF = hospitalization for heart failure; HHS = hyperosmolar hyperglycemic state; HR = hazard ratio; IDet = insulin detemir; IGlar = insulin glargine; MI = myocardial infarction; NHIRD = National Health Insurance Research Database; PCI = percutaneous coronary intervention; PSM = propensity score matching; T2DM = type 2 diabetes mellitus.

Topics: Brain Ischemia; Cardiovascular Diseases; Cohort Studies; Diabetes Mellitus, Type 2; Humans; Insulin Detemir; Insulin Glargine; Percutaneous Coronary Intervention; Retrospective Studies; Stroke; Taiwan; Treatment Outcome

Type 2 diabetes (T2D) is rapidly increasing in incidence and has significant social and economic costs. Given the increasing cost of complications, even relatively short delays in the onset of T2D can significantly reduce long-term complications and costs. Equally, recent studies have shown the onset of T2D can be delayed by use of long-acting insulin, despite the risk and concomitant low adherence. Thus, there is a strong potential motivation to develop models of long-acting insulin analogues to enable safe, effective use in model-based dosing systems. In particular, there are no current models of long-acting insulin Detemir and its unique action for model-based control. The objective of this work is to develop a first model of insulin Detemir and its unique action, and validate it against existing data in the literature.. This study develops a detailed compartment model for insulin Detemir. Model specific parameters are identified using data from a range of published clinical studies on the pharmacokinetic of insulin Detemir. Model validity and robustness are assessed by identifying the model for each study and using average identified parameters over several dose sizes and study cohorts. Comparisons to peak concentration, time of peak concentration and overall error versus measured plasma concentrations are used to assess model accuracy and validity.. Almost all studies and cohorts fit literature data to within one standard deviation of error, even when using averaged identified model parameters. However, there appears to be a noticeable dose dependent dynamic not included in this first model, nor reported in the literature studies.. A first model of insulin Detemir including its unique albumin binding kinetics is derived and provisionally validated against clinical pharmacokinetic data. The pharmacokinetic curves are suitable for model-based control and general enough for use. While there are limitations in the studies used for validation that prevent a more complete understanding, the results provide an effective first model and justify the design and implementation of further, more precise human trials.

Topics: Adult; Algorithms; Computational Biology; Computer Simulation; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin Detemir; Male; Middle Aged; Patient Compliance; Young Adult

To evaluate the effectiveness of the different insulin therapies on obstetrics-fetal outcomes in women with pregestational diabetes mellitus. We enrolled 147 pregnant women with pre-existing type 1 or 2 diabetes mellitus. Clinical and biochemical parameters were analysed in relation to obstetric and fetal outcomes. 14.2% received treatment with Neutral Protamine Hagedorn insulin and short-acting insulin analogues; 19% with premixed human insulin; 40.1% with insulin glargine and lispro, 6.2% with detemir and aspart and 20% with continuous subcutaneous insulin infusion. All 5 types of treatment achieved a reduction of the mean HbA1c during pregnancy (p = 0.01). Pre-pregnancy care was carried out for 48% of patients. We found no statistically significant differences between the different insulin therapies and the obstetric-fetal outcomes. In conclusión, the different insulin therapies used in patients with pregestational diabetes mellitus does not seem to affect obstetric-fetal outcomes.

Topics: Adult; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Drug Combinations; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Detemir; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Pregnancy; Pregnancy Outcome

A 69-year-old woman with uncontrolled type 2 diabetes mellitus was admitted in the hospital for the management of urosepsis. Patient was overdosed with detemir insulin 1000 units inadvertently. Care provider was confused with volume and dose of the insulin by using insulin vial. Blood sugars were monitored closely every 30 min-1 hour for 24 hours. Patient was treated with dextrose 5% and 10% continuous infusion; and hydrocortisone 75 mg every 6 hours for 24 hours. The lowest blood sugar reached was 142 mg/dL (7.9 mmo/L). Patient did not develop hypoglycaemia. Proper safety measures and mandatory nurse education about administration of insulin were implemented to prevent future occurrences.

Topics: Aged; Anti-Inflammatory Agents; Blood Glucose; Diabetes Mellitus, Type 2; Drug Overdose; Female; Glucose; Health Personnel; Hospitalization; Humans; Hydrocortisone; Iatrogenic Disease; Infusions, Intravenous; Insulin Detemir; Sweetening Agents; Treatment Outcome; Urinary Tract Infections

Hyperglycemia in the hospital setting is associated with increased morbidity and mortality. In an attempt to cut costs, some hospitals implement policies to substitute all glargine orders with detemir.. To examine how the substitution of glargine with detemir affects inpatient blood glucose control.. Medical records were retrospectively analyzed to investigate the effect of a hospital formulary change at a semi-urban underserved hospital that substituted detemir for glargine on a 1:1 dosing basis. The study evaluated blood glucose control from September 6, 2015, to September 5, 2016, before substitution and from September 6, 2016, to September 5, 2017, after the substitution began. Patients were included in the study if they were older than 18 years, received glargine before admission, and had type 1 or 2 diabetes mellitus. Patients were excluded if they were pregnant, did not receive long-acting insulin, or lacked regular blood glucose testing. The medical records were analyzed for mean glucose levels, hypoglycemic events, and short-acting insulin administration amounts.. A total of 318 patients met criteria and were included in the retrospective analysis-134 patients received detemir and 184 patients received glargine. The mean glucose levels in the morning were 133.8 mg/dL for patients receiving detemir and 145.8 mg/dL for patients receiving glargine (95% CI, 126.972-140.753; P=.013). The mean blood glucose levels in the afternoon were 171.6 mg/dL for patients receiving detemir and 172.1 mg/dL for patients receiving glargine (95% CI, 162.955-180.344; P=.938). The mean blood glucose levels in the evening were 162.5 mg/dL for patients receiving detemir and 163.3 mg/dL for patients receiving glargine (95% CI, 153.654-171.315; P=.897). The mean blood glucose levels at night were 176.1 mg/dL for patients receiving detemir and 174.7 mg/dL for patients receiving glargine (95% CI, 167.797-184.474; P=.788). No significant difference in sliding scale insulin was required between the patient groups (0.16 U/kg insulin aspart in detemir group vs 0.18 U/kg aspart in glargine; 95% CI, 0.154-0.189; P=.297). There was no significant difference between the patient groups in regard to hypoglycemic events (45% glargine vs 49% detemir; P=.59).. Substituting detemir for glargine did not adversely affect inpatients' blood glucose control.

Topics: Aged; Aged, 80 and over; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Inpatients; Insulin Detemir; Insulin Glargine; Male; Middle Aged; Retrospective Studies

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 describe primary care physicians' (PCPs) perceptions of patient reactions and concerns about insulin initiation and identify opportunities for increased support.. Cross-sectional, online survey of PCPs prescribing basal insulin to adults with type 2 diabetes mellitus (T2DM). PCPs were identified from administrative claims of a large commercial health plan and descriptive results of PCP responses were reported.. PCPs (N=100) treated an average of 17 patients receiving insulin during a typical week. More than 85% of insulin initiation recommendations originated with PCPs. Most offered glucose monitoring instructions (96%) and advice on diet, exercise, and diabetes management (96%); 35% provided insulin titration algorithms; 93% reported that patients often or always took their insulin daily within 3 months of initiation; 31% of PCPs reported monthly office contacts with patients for the first 3 months; 16% reported no outreach efforts; fewer than 20% connected patients with support groups. When starting basal insulin, PCPs reported patients feeling personal failure regarding their diabetes treatment (33% often/always) and lacking confidence in their ability to manage insulin therapy (38% often/always).. Study results identify additional opportunities for assisting patients in making the transition to insulin, including more frequent direct outreach to monitor insulin usage.

Topics: Adolescent; Adult; Aged; Attitude of Health Personnel; Biomarkers; Blood Glucose; Communication; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Health Care Surveys; Health Knowledge, Attitudes, Practice; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Male; Middle Aged; Patient Education as Topic; Physician-Patient Relations; Physicians, Primary Care; Practice Patterns, Physicians'; Transitional Care; Treatment Outcome; Young Adult

This study examines the relationship between glycated haemoglobin (A1C) levels and treatment persistence with, or time to discontinuation of, basal insulin in patients with type 2 diabetes (T2D) newly initiating insulin. Claims data were extracted from the Optum Clinformatics database from January 2010 to June 2015. Adult patients with T2D initiating insulin glargine 100 U/mL (Gla-100) or insulin detemir (DET) with ≥1 A1C measurement during 12-month baseline and 18-month follow-up periods were included. Patients with a refill gap of >90 days were considered non-persistent; otherwise, patients were considered persistent with insulin. The main outcome was A1C, measured closest to the end of each quarter during the follow-up period. A total of 3993 of 109 934 patients met the inclusion criteria (43.0% persistent; 57.0% non-persistent). Persistent patients were older (54.7 vs 52.7 years; P < .001), were more likely to be male (59.4% vs 54.4%; P = .002), and had significantly lower mean unadjusted A1C values at 18 months (8.26% vs 8.60%; P < .001) and quarterly. Only 43.0% of adults initiating basal insulin persisted with treatment for 18 months, with earlier discontinuation associated with higher A1C.

Topics: Age Factors; Cohort Studies; Diabetes Mellitus, Type 2; Drug Monitoring; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Detemir; Insulin Glargine; Insurance, Health; Male; Medicare; Medication Adherence; Middle Aged; Retrospective Studies; Sex Characteristics; United States

Gestational diabetes mellitus (GDM) occurs in 2-9% of all pregnancies. Evidence suggests that the use of insulin in treating hyperglycemia in GDM patients reduces the risk of perinatal morbidity. Pregnancy is an exciting time in a woman's life. However, once patient is diagnosed with GDM, she will be managed more intensively. GDM is managed using diet and exercise but one in six women with GDM requires insulin. A 35-year-old woman at the 14th gestational week of her tenth pregnancy was seen for routine prenatal care. She had the history of nine consecutive spontaneous abortions. Patient was hospitalized and based on the revealed glucose values insulin therapy was initiated with long-acting insulin analogue - Levemir and rapid-acting insulin analogue - NovoRapid. Patient's diabetes was compensated on insulin therapy. Follow-ups were planned at intervals of 1-2 weeks depending on the glucose levels. This is the case report of a GDM in a high-risk patient. She's at the 21st gestational weeks and has passed "delicate weeks". At her 21st week of gestation patient's glucose levels are compensated on insulin therapy and she is feeling well. In this unusual case report, no insulin therapy had been started during previous pregnancies, so we managed to achieve a good glycemic control with insulin treatment. This could be one of the factors that could help a normal pregnancy and delivery. The discussion should be focusing on early screening and proper treatment for GDM.

Topics: Abortion, Spontaneous; Adult; Diabetes Mellitus, Type 2; Diabetes, Gestational; Drug Therapy, Combination; Female; Humans; Hypoglycemic Agents; Insulin Aspart; Insulin Detemir; Mutation; Pregnancy; Risk Factors

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

The mitogenic potential of analog insulins due to their different insulin-like growth factor-1 (IGF1) receptor affinity is a situation that causes concern related to cancer risk. We aimed to examine the changes in the serum IGF1 levels formed by insulin glargine and detemir in the insulin-naive type 2 diabetic patients.. The serum total IGF1 levels of the 62 insulin-naive type 2 diabetic patients were studied before and after 12 weeks of the started treatment with basal insulin analogs. Twenty-two and twenty patients (Group I and II) using the single-dose and double-dose insulin detemir and twenty patients (Group III) using insulin glargine were evaluated.. In Group I and Group II, the average 8.5% and 0.1% increases and in the Group III, 6.5% decreases were determined in the IGF1 values. The IGF1 changes were significant in the men but not in the women.. In our study, it was determined that the insulin glargine depressed the serum IGF1 levels much more when compared to the insulin detemir. This result can be evaluated as the in vivo reflection of the in vitro findings related to the fact that the IGF1 receptor affinity of the glargine is higher.

Topics: Adult; Aged; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Down-Regulation; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin-Like Growth Factor I; Male; Middle Aged; Time Factors; Treatment Outcome

An economic evidence is a vital tool that can inform the decision to use costly insulin analogs. This study aimed to evaluate long-term cost-effectiveness of insulin detemir (IDet) compared with insulin glargine (IGlar) in type 2 diabetes (T2DM) from the Thai payer's perspective.. Long-term costs and outcomes were projected using a validated IMS CORE Diabetes Model, version 8.5. Cohort characteristics, baseline risk factors, and costs of diabetes complications were derived from Thai data sources. Relative risk was derived from a systematic review and meta-analysis study. Costs and outcomes were discounted at 3% per annum. Incremental cost-effectiveness ratio (ICER) was presented in 2015 US Dollars (USD). A series of one-way and probabilistic sensitivity analyses were performed.. IDet yielded slightly greater quality-adjusted life years (QALYs) (8.921 vs 8.908), but incurred higher costs than IGlar (90,417.63 USD vs 66,674.03 USD), resulting in an ICER of ∼1.7 million USD per QALY. The findings were very sensitive to the cost of IDet. With a 34% reduction in the IDet cost, treatment with IDet would become cost-effective according to the Thai threshold of 4,434.59 USD per QALY.. Treatment with IDet in patients with T2DM who had uncontrolled blood glucose with oral anti-diabetic agents was not a cost-effective strategy compared with IGlar treatment in the Thai context. These findings could be generalized to other countries with a similar socioeconomics level and healthcare systems.

Topics: Aged; Blood Glucose; Comorbidity; Computer Simulation; Cost-Benefit Analysis; Diabetes Complications; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Male; Middle Aged; Models, Econometric; Quality-Adjusted Life Years; Risk Factors; Thailand

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

The Observational Registry of Basal Insulin Treatment (ORBIT) study evaluated the safety of basal insulin (BI) in real-world settings in China.. We analyzed 9002 patients with type 2 diabetes (T2D) inadequately controlled with oral hypoglycemic agents from 8 geographic regions and 2 hospital tiers in China who initiated and maintained BI treatment. Body weight and hypoglycemic episodes were recorded at baseline and 3 and 6 months. Serious adverse events (SAEs) were recorded at 3 and 6 months.. Age, gender, inpatient/outpatient status, body mass index, glycated hemoglobin (HbA1c) at baseline and at the end of study, T2D duration, microvascular complications, BI type, combination with insulin secretagogues, self-monitoring of blood glucose frequency, and insulin dosage, all predicted hypoglycemia. BI use generally did not induce significant weight gain (0.02 kg); weight gain with insulin detemir (-0.30 kg) was less than that with neutral protamine Hagedorn (NPH) insulin (0.20 kg) or insulin glargine (0.05 kg). Overall, general hypoglycemia incidence (5.6% vs. 7.7%) and annual event rate (1.6 vs. 1.8) were similar before and after BI initiation, whereas a slight decrease was noted in severe hypoglycemia incidence (0.6%-0.3%) and frequency (0.05-0.03 events/patient-year). The general hypoglycemia rate was lowest with insulin glargine, whereas there was no significant difference in severe hypoglycemia among the three BI groups. Overall, 3.5% of patients had at least one SAE during the study. Most SAEs were found to be unrelated to BI treatment.. Real-world BI use, particularly insulin detemir and glargine, was associated with only slight weight gain and low hypoglycemia risk in patients with T2D in China.

Topics: Adult; Aged; Blood Glucose; China; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Male; Middle Aged; Registries; Risk Factors; Treatment Outcome

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 evaluate the effectiveness and safety of insulin detemir treatment as add-on therapy in a real-world setting of Lebanese insulin naïve persons, with type 2 diabetes poorly controlled on oral antidiabetic drugs (OADs).. Our study was a prospective, observational study representing the Lebanese arm of the multinational prospective and observational study involving 2,155 persons across Near East countries, Lebanon, Pakistan, Israel and Jordan. Effectiveness endpoints were changes in HbA1c, fasting and post-prandial glucose (FPG, PPG) after 24 weeks of treatment with insulin detemir in eligible persons. Safety endpoints were number of hypoglycemic events, incidence of adverse drug reactions (ADRs), serious ADRs, adverse events, and body weight change between baseline and end of treatment.. 868 persons were included (mean age: 59.5 ± 10.4 years, men: 55.3%). Glycemic control improved with significant reduction in mean HbA1c from 9.7 ± 1.6% to 7.2 ± 1% (P<.0001). The percentage of persons who achieved the target of HbA1c<7% increased from .7% at baseline to 39% at week 24. Mean FPG decreased significantly from 213.7 ± 60.1 mg/dL to 120.3 ± 25.7 mg/dL (P<.001), and mean PPG from 271 ± 65.3 mg/dL to 158.1 ± 36.4 mg/dL (P<.0001). The rate of major hypoglycemic episodes decreased from .1498 at baseline to .0448 at week 24. Three adverse events but no ADR or serious ADR were reported. Body weight decreased from 80.4±13.2 Kg to 79.9±12.5 Kg (P<.0001).. Initiating insulin detemir in a clinical health care setting among Lebanese with type 2 diabetes mellitus on OADs improves glycemic control with no increase in hypoglycemia, adverse events or weight compared with baseline.

Topics: Administration, Oral; Adult; Aged; Blood Glucose; Developing Countries; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged; Prospective Studies; Young Adult

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

Basal insulin and DPP4 inhibitors are both possible options in patients with type 2 diabetes failing to oral drugs. The identification of clinical predictors of success with either one of the two approaches could be of help in personalizing therapy.. The retrospective study was performed on a consecutive series of patients with type 2 diabetes (n = 1,002) failing to at least one oral agent, who had been prescribed either basal insulin or DPP4 inhibitors in the previous 2 years, with a duration of follow-up of at least 6 months. Clinical predictors of success after 6 months from the beginning of second-line treatment were identified in the cohort.. Among patients receiving a prescription of basal insulin, the proportion of therapeutic success at 6 months was 26.5 %. At multivariate analysis, a higher age and BMI, and a lower duration of diabetes were associated with success, as well as treatment with acarbose; conversely, a history of ischemic heart disease was associated with failure. Prescription of DPP4 inhibitors produced a therapeutic success in 24.8 % of cases. At multivariate analysis, success was associated with a lower baseline HbA1c and duration of diabetes, and a higher BMI and comorbidity; in addition, a lower success rate was found in women after adjusting for other confounders.. The present data support the view that insulin treatment is preferable in patients with severe hyperglycemia, failing to one or more drugs, whereas DPP4 inhibitors appear to be more useful in those with comorbid conditions.

Topics: Aged; Aged, 80 and over; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Resistance; Drug Therapy, Combination; Female; Humans; Hypoglycemic Agents; Insulin Detemir; Male; Middle Aged; Prognosis; Retrospective Studies; Salvage Therapy; Treatment Outcome

Describe the experience in the primary care setting with insulin detemir in patients with poorly controlled type2 diabetes mellitus that need to add-on insulin to their oral antidiabetic drug therapy.. Prospective observational study of 6 months of follow up, performed in 10 countries. In Spain, participating sites were only from the primary care setting. Eligible patients were those with poorly controlled type2 diabetes mellitus adding-on once-daily insulin detemir to their existing oral antidiabetic therapy in the month prior to their enrollment. The change of Hb1Ac and of weight at the end of the study and the incidence of hypoglycemia and adverse reactions, were analyzed. We report the results obtained in the Spanish cohort.. Overall 17,374 patients were included, 973 in Spain [mean age 64.8 years (SE 12); duration of diabetes 9.4 years (SE 6.2); Hb1Ac 8.9% (DE 1.4)]. In the sample analyzed for efficacy (n=474) the mean change of Hb1Ac was -1.6% (95%CI: -1.75 to -1.42; P<.001), mean change of weight was -2.9 kg (95%CI: -3.72 to -2.08; P<.001). Only one episode of severe hypoglycemia was reported, which was also the only serious adverse reaction reported in the study. The incidence rate of non-severe hypoglycemia was 2.44 events/patient-year.. In this cohort of patients with type 2 diabetes mellitus receiving newly initiated insulin therapy, once-daily detemir improved the glycemic control, with low incidence of hypoglycemia and a significant reduction of the weight.

Topics: Aged; Blood Glucose; Cohort Studies; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Male; Middle Aged; Prospective Studies; Spain

To assess resource utilization associated with severe hypoglycaemia across three insulin regimens in a large phase 3a clinical programme involving people with Type 1 diabetes treated with basal-bolus insulin, people with Type 2 diabetes treated with multiple daily injections and people with Type 2 diabetes treated with basal-oral therapy.. Data relating to severe hypoglycaemia events (defined as episodes requiring external assistance) from the insulin degludec and insulin degludec/insulin aspart programme (15 trials) were analysed using descriptive statistics. Comparators included insulin glargine, biphasic insulin aspart, insulin detemir and sitagliptin. Mealtime insulin aspart was used in some regimens. This analysis used the serious adverse events records, which documented the use of ambulance/emergency teams, a hospital/emergency room visit ≤ 24 h, or a hospital visit > 24 h.. In total, 536 severe hypoglycaemia events were analysed, of which 157 (29.3%) involved an ambulance/emergency team, 64 (11.9%) led to hospital/emergency room attendance of ≤ 24 h and 36 (6.7%) required hospital admission (> 24 h). Although there were fewer events in people with Type 2 diabetes compared with Type 1 diabetes, once a severe episode occurred, the tendency to utilize healthcare resources was higher in Type 2 diabetes vs. Type 1 diabetes. A higher proportion (47.6%) in the basal-oral therapy group required hospital treatment for > 24 h versus the Type 1 diabetes (5.0%) and Type 2 diabetes multiple daily injections (5.3%) groups.. This analysis suggests that severe hypoglycaemia events often result in emergency/ambulance calls and hospital treatment, incurring a substantial health economic burden, and were associated with all insulin regimens.

Topics: Administration, Oral; Adult; Clinical Trials, Phase III as Topic; Cohort Studies; Costs and Cost Analysis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Health Care Costs; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Middle Aged; Severity of Illness Index; Sitagliptin Phosphate

The safe and effective conversion of human regular U-500 insulin (U-500R) to basal and bolus U-100 (insulin detemir and insulin lispro, respectively) in a patient undergoing a significant dietary change in preparation for bariatric surgery is described.. Conversion from U-100 to U-500R insulin has been described in the literature. There is, however, a paucity of information describing the reverse conversion (i.e., from U-500R to U-100 insulin). Whether converting to or from U-500R, patient safety is a primary concern. A 51-year-old Caucasian woman with a 10-year history of type 2 diabetes mellitus, hypertension, and gastroparesis who was scheduled to undergo bariatric surgery was converted from U-500R to insulin detemir and insulin lispro preoperatively while undergoing significant diet changes. The patient's blood glucose values, diet, and activity levels were closely monitored daily by the interprofessional team over a 10-day preoperative period during which her regular diet was changed to a very low-calorie, high-protein diet; insulin doses were adjusted accordingly. Throughout this process, the patient did not experience any major hypoglycemic episodes. Close collaboration among interprofessional team members and a strong partnership with the patient were considered key factors in the successful conversion of insulin therapy.. Subcutaneous insulin therapy in a woman preparing for bariatric surgery was safely converted from U-500R to basal therapy with U-100 insulin detemir and with as-needed boluses of U-100 insulin lispro. This occurred as the patient switched from a regular diet to a low-calorie, high-protein diet.

Topics: Bariatric Surgery; Caloric Restriction; Diabetes Mellitus, Type 2; Dietary Proteins; Drug Administration Routes; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Lispro; Middle Aged

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

The aim of the present prospective observational study was to assess long-term efficacy and safety of insulin degludec as a part of a basal-bolus therapy for Japanese patients with type 1 or type 2 diabetes in routine clinical practice.. In the present study, 93 type 1 diabetes patients and 135 type 2 diabetes patients treated with insulin glargine or detemir were switched from their basal insulin to insulin degludec. The primary end-points were the changes in glycated hemoglobin (HbA1c) from baseline at 3, 6 and 12 months. The secondary end-points were changes in body mass index, insulin dose, frequency of hypoglycemia and adverse events.. HbA1c levels from baseline were significantly reduced at 3, 6, and 12 months by 0.4, 0.4 and 0.3% in type 1 diabetes patients, respectively, and by 0.5, 0.5 and 0.3% in type 2 diabetes patients, respectively. Body mass index in type 1 diabetes patients increased significantly (P < 0.05), whereas that in type 2 diabetes patients did not change. Basal insulin dose decreased significantly at 3 months after switching (P < 0.05), and returned baseline dose at 12 months in type 1 diabetes and type 2 diabetes patients. The frequency of both total and nocturnal hypoglycemia decreased significantly in type 1 diabetes and type 2 diabetes patients (P < 0.05). The result of multiple regression analysis showed that baseline HbA1c was a significant independent variable of the percentage change in HbA1c with switching.. In both type 1 diabetes and type 2 diabetes patients, switching from insulin glargine or insulin detemir to insulin degludec led to improvement of glycemic control with a significant reduction of hypoglycemia.

Topics: Aged; Asian People; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Japan; Male; Middle Aged; Outpatients; Prospective Studies; Treatment Outcome

Topics: Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Drug Costs; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Polyethylene Glycols

The present subanalysis of the Study of Once Daily Levemir (SOLVE) study was to evaluate the safety and efficacy of once-daily insulin detemir as add-on to oral antidiabetic drugs (OADs) in Chinese type 2 diabetes patients according to body mass index in a real-life setting.. In all, 3272 eligible patients who were treated with diet, exercise, and one or more OAD were prescribed once-daily insulin detemir by their physician according to routine clinical practice and were followed-up for 24 weeks. The incidence of serious adverse reactions (SADRs), including major hypoglycemia, was the primary endpoint. Subanalyses were performed on patients in the following BMI groups: normal weight (BMI < 25 kg/m2); overweight (25 ≤ BMI < 30 kg/m2); and obese (BMI ≥ 30 kg/m2).. No SADRs were reported during the study. Significant improvements in glycemic levels were observed in all subgroups. For normal weight, overweight, and obese patients, the mean change in HbA1c (%/[mmol/mol]) was -1.26/-14, -1.09/-12, and -1.06/-12, respectively. The mean change in fasting plasma glucose in normal weight, overweight, and obese patients was -2.77, -2.57, and -2.71 mmol/L, respectively. Slight weight gain (0.25 kg), slight weight loss (-0.36 kg), and weight loss (-1.32 kg) were observed in the normal weight, overweight, and obese patients, respectively (P < 0.001). Linear regression analysis revealed a negative relationship between weight change and baseline BMI (slope = -0.16; P < 0.001).. Once-daily insulin detemir as add-on to OADs in Chinese patients with type 2 diabetes showed effective glycemic control and a low risk of hypoglycemia. Weight-neutral effects were observed in different BMI subgroups.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Body Mass Index; Body Weight; China; Cohort Studies; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin, Long-Acting; International Agencies; Male; Middle Aged; Prognosis; Young Adult

Insulin detemir is a long-acting insulin analogue and may represent a valuable treatment option for diabetic cats. So far, only one study addressing detemir treatment of diabetic cats has been published, and this was based on an intensive blood glucose monitoring protocol. The aim of the current, retrospective study was to evaluate the effect of detemir therapy in diabetic cats in a general clinical setting. Fourteen diabetic cats with a follow-up period of at least 3 months were included. Data were collected from medical records at the University Hospital for Companion Animals, University of Copenhagen, Denmark. Thirteen of 14 cats achieved moderate or excellent control of clinical symptoms within the initial 3 months of detemir therapy, including five cats previously treated unsuccessfully with other types of insulin. Clinical improvements were noted after 1 month of therapy and continued over time. Three cats achieved remission within the initial 3 months and none experienced a diabetic relapse during the study period. One cat achieved remission after 13 months of therapy. Improvements in clinical symptoms were markedly better than indicated by blood glucose and serum fructosamine concentrations. The safety of detemir was very high, with only two reported episodes of clinical hypoglycaemia, neither of which required veterinary attention. Based on these results detemir can be recommended for the treatment of diabetic cats, including cats previously treated unsuccessfully with other types of insulin.

Topics: Animals; Blood Glucose; Cat Diseases; Cats; Denmark; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Follow-Up Studies; Hypoglycemic Agents; Insulin Detemir; Insulin, Long-Acting; Retrospective Studies; Treatment Outcome

To evaluate real-world clinical outcomes for switching basal insulin analogues [insulin glargine (GLA) and insulin detemir (DET)] among US patients with type 2 diabetes mellitus (T2DM).. Using the GE Centricity Electronic Medical Records database, this retrospective study examined two cohorts: cohort 1, comprising patients previously on GLA and then either switching to DET (DET-S) or continuing with GLA (GLA-C); and cohort 2, comprising patients previously on DET and then either switching to GLA (GLA-S) or continuing with DET (DET-C). Within each cohort, treatment groups were propensity-score-matched on baseline characteristics. At 1-year follow-up, insulin treatment patterns, glycated haemoglobin (HbA1c) levels, hypoglycaemic events, weight and body mass index (BMI) were evaluated.. The analysis included 13 942 patients: cohort 1: n = 10 657 (DET-S, n = 1797 matched to GLA-C, n = 8860) and cohort 2: n = 3285 (GLA-S, n = 858 matched to DET-C, n = 2427). Baseline characteristics were similar between the treatment groups in each cohort. At 1-year follow-up, in cohort 1, patients in the DET-S subgroup were significantly less persistent with treatment, more likely to use a rapid-acting insulin analogue, had higher HbA1c values, lower HbA1c reductions and lower proportions of patients achieving HbA1c <7.0 or <8.0% compared with patients in the GLA-C subgroup, while hypoglycaemia rates and BMI/weight values and change from baseline were similar in the two subgroups. In cohort 2, overall, there were contrasting findings between patients in the GLA-S and those in the DET-C subgroup.. This study showed contrasting results when patients with T2DM switched between basal insulin analogues, although these preliminary results may be subject to limitations in the analysis. Nevertheless, this study calls into question the therapeutic interchangeability of GLA and DET, and this merits further investigation.

Topics: Aged; Body Mass Index; Body Weight; Databases, Factual; Diabetes Mellitus, Type 2; Drug Substitution; Electronic Health Records; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Insulin, Short-Acting; Male; Middle Aged; Retrospective Studies; Treatment Outcome; United States

There is limited evidence with respect to the cost-effectiveness of starting insulin in people with diabetes outside the 'western' world. The aim of this study was to assess the cost-effectiveness of starting basal insulin treatment with insulin detemir in people with type 2 diabetes (T2D) inadequately controlled on oral glucose-lowering drugs (OGLDs) in Mexico, South Korea, India, Indonesia, and Algeria.. The IMS CORE Diabetes Model was used to project clinical and cost outcomes over a 30-year time horizon. Clinical outcomes, baseline characteristics and health state utility data were taken from the A1chieve study. A 1-year analysis was also conducted based on treatment costs and quality-of-life data. Incremental cost-effectiveness ratios (ICERs) were expressed as a fraction of GDP per capita, and WHO-CHOICE recommendations (ICER < 3.0) used to define cost-effectiveness.. Starting insulin detemir was associated with a projected increase in life expectancy (≥1 year) and was considered cost-effective in all of the studied populations with ICERs of -0.02 (Mexico), 0.00 (South Korea), 0.48 (India), 0.12 (Indonesia), and 0.88 (Algeria) GDP/quality-adjusted life-year. Cost-effectiveness was maintained after conducting sensitivity analyses in the 30-year and 1-year analyses. A projected increase in treatment costs was partially offset by a reduction in complications. The difference in overall costs between insulin detemir and OGLDs alone was USD518, 1431, 3510, 15, and 5219, respectively.. Changes in clinical outcomes associated with starting insulin detemir in insulin-naïve individuals with T2D resulted in health gains that made the intervention cost-effective in five countries with distinct healthcare resources.

Topics: Adult; Aged; Cost-Benefit Analysis; Developing Countries; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Gross Domestic Product; Humans; Hypoglycemic Agents; Insulin Detemir; Life Expectancy; Male; Mexico; Middle Aged; Models, Econometric; Quality-Adjusted Life Years

Topics: Aged; Diabetes Mellitus, Type 2; Drug Substitution; Edema; Humans; Insulin Detemir; Insulin Glargine; Lower Extremity; Male

Topics: Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin, Long-Acting; Placenta; Pregnancy; Pregnancy in Diabetics

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

Diabetes mellitus (DM) is a common endocrinopathy in cats that appears to be increasing in prevalence. The prognosis for affected cats can be good when the disease is well managed, but clinical management presents challenges, both for the veterinary team and for the owner. These ISFM Guidelines have been developed by an independent, international expert panel of clinicians and academics to provide practical advice on the management of routine (uncomplicated) diabetic cats.. Although the diagnosis of diabetes is usually straightforward, optimal management can be challenging. Clinical goals should be to limit or eliminate clinical signs of the disease using a treatment regimen suitable for the owner, and to avoid insulin-induced hypoglycaemia or other complications. Optimising bodyweight, feeding an appropriate diet and using a longer acting insulin preparation (eg, protamine zinc insulin, insulin glargine or insulin detemir) are all factors that are likely to result in improved glycaemic control in the majority of cats. There is also some evidence that improved glycaemic control and reversal of glucose toxicity may promote the chances of diabetic remission. Owner considerations and owner involvement are an important aspect of management. Provided adequate support is given, and owners are able to take an active role in monitoring blood glucose concentrations in the home environment, glycaemic control may be improved. Monitoring of other parameters is also vitally important in assessing the response to insulin. Insulin adjustments should always be made cautiously and not too frequently--unless hypoglycaemia is encountered.. The Panel has produced these Guidelines after careful review of the existing literature and of the quality of the published studies. They represent a consensus view on practical management of cats with DM based on available clinical data and experience. However, in many areas, substantial data are lacking and there is a need for better studies in the future to help inform and refine recommendations for the clinical management of this common disease.

Topics: Animals; Cat Diseases; Cats; Diabetes Mellitus, Type 2; Drug Administration Schedule; Hypoglycemic Agents; Insulin Detemir; Insulin, Long-Acting; International Agencies; Practice Guidelines as Topic; Societies, Medical

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

To evaluate the effectiveness and safety on once-daily (OD) insulin detemir (IDet) in Chinese patients with type 2 diabetes mellitus (T2DM) who were treated with different types or combinations of oral anti-diabetic drugs (OADs).. The SOLVE™ study was a 24-week observational study on the initiation of IDet OD in T2DM patients with uncontrolled hyperglycemia on diet, exercise, and one or more OADs. Subjects were grouped based on the numbers of OADs taken before (>2-OAD, 2-OAD, and 1-OAD groups). Efficacy and safety endpoints were evaluated and compared in different groups.. This study includes 3 272 patients, among them 464 (14.2%) were treated with more than 2 OADs, 1511 (46.2%) with 2 OADs, and 1 218 (37.2%) with 1 OAD before the study. The mean glycosylated hemoglobin A1c (HbA1c) was 8.4%, 8.3%, 8.4% at baseline, and 7.3%, 7.2%, 7.1% at the end of 24-week in each 3 groups (all P<0.001 vs. baseline values). The HbA1c reductions were not statistically significant different among groups. Body weight tended to decrease in patients from all groups, however, only that in the 2-OAD group reached statistically significance. No major hypoglycaemia events were reported. However, the overall minor hypoglycaemia rate in the 2-OAD group was higher at the end of the study than that at baseline (P<0.05). No differences in the rate of nocturnal minor hypoglycaemia were observed in all groups after IDet treatment.. Initiation of IDet OD was effective and well-tolerated in Chinese patients with T2DM whose glycemia was poorly controlled on OADs irrespective of the number of OADs taken before. (registration number NCT00825643).

Topics: Blood Glucose; China; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome

The addition of basal insulin to oral antidiabetics (OADs) is described by a large number of guidelines and commonly used in clinical practice as a way to start insulin therapy in patients with type 2 diabetes mellitus in order to maximize compliance and minimise the impact of side effects (mainly hypoglycemia and body weight increase).. SOLVE™ was a 24-week international observational study conducted in 10 countries (including Italy) for the evaluation of the safety and effectiveness of once-daily insulin detemir as add-on therapy in patients with type 2 diabetes mellitus (T2DM) already treated with one or more OADs. The Italian arm of the Solve™ Study aimed to evaluate the safety and the effectiveness of once-daily insulin detemir in combination with OAD agents for the treatment of patients with T2DM in the Italian outpatient specialist setting. The primary endpoint was to assess the incidence of serious adverse drug reactions (SADRs) including in the specific major hypoglycemic events during 24 weeks of once-daily insulin detemir treatment.. A total of 4625 patients were enrolled in the study by 223 Italian centres for diabetes care. At baseline the mean (±SD) demographic characteristics of the patients were: age 66.5 (±10.0) years, duration of diabetes 13.25 (±8.14) years, weight 78.95 (±15.86) kg and BMI 29.5 (±5.0) kg/m2. At the end of the study, 3 SADRs (of which 2 were major hypoglycemia) were reported in 2 patients (<0.1%). The percentage of patients with at least 1 minor hypoglycemic event during the 4 weeks preceding insulin initiation was 3.6%. Following insulin initiation, 5.7% (as recorded at baseline visit) had at least 1 minor hypoglycemic event, which decreased slightly by the end of the study compared to baseline (4.8%). In addition, before insulin initiation the mean (±SD) glycemic control values were: fasting plasma glucose (FPG) 11.43 (±3.2) mmol/L and HbA1c 9.16% (±1.46). At the end of the study, HbA1c was reduced by 1.35% (±1.57) (P<0.001), FPG was reduced by 3.34 mmol/L (P<0.001) and the percentage of patients with HbA1c<7% was 21.9%. A mean reduction of 0.52 kg of body weight (P<0.001) was observed compared to before insulin initiation; the body weight reduction was more pronounced in patients with higher BMI before insulin initiation (-1.0 kg for 30

Topics: Aged; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Endpoint Determination; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Italy; Male; Middle Aged

OBJECTIVE To determine a cutoff score for clinically meaningful fear of hypoglycemia (FoH) on the Hypoglycemia Fear Survey Worry subscale (HFS-W). RESEARCH DESIGN AND METHODS Data on the HFS-W, history of hypoglycemia, emotional well-being (World Health Organization-5 well-being index), and distress about diabetes symptoms (Diabetes Symptom Checklist-Revised) were available from Dutch patients with type 2 diabetes who were treated with oral medication or insulin (n = 1,530). Four criteria were applied to define a threshold for clinically meaningful FoH: 1) modal score distribution (MD criterion), 2) scores 2 SDs above the mean (SD criterion), 3) concurrent validity with severe hypoglycemia and suboptimal well-being (CV criterion), and 4) an elevated score (≥3) on more than one HFS-W item (elevated item endorsement [EI criterion]). Associations between the outcomes of these approaches and a history of severe hypoglycemia and suboptimal well-being were studied. RESULTS Of the 1,530 patients, 19% had a HFS-W score of 0 (MD criterion), and 5% reported elevated FoH (HFS-W ≥ mean + 2 SD; SD criterion). Patients with severe hypoglycemia reported higher HFS-W scores than those without (25 ± 20 vs. 15 ± 17; P < 0.001). Patients with suboptimal well-being reported higher HFS-W scores than those with satisfactory well-being (20 ± 18 vs. 13 ± 15; P < 0.001, CV criterion). Elevated FoH (defined by the EI criterion) was seen in 26% of patients. The SD and EI criteria were the strongest associated with history of severe hypoglycemia. The EI criterion was the strongest associated with suboptimal well-being. CONCLUSIONS Although no definite cutoff score has been determined, the EI criterion may be most indicative of clinically relevant FoH in this exploratory study. Further testing of the clinical relevance of this criterion is needed.

Topics: Aged; Diabetes Mellitus, Type 2; Fear; Female; Health Surveys; Humans; Hypoglycemia; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Prevalence; Psychiatric Status Rating Scales; Regression Analysis; Risk Factors; Sulfonylurea Compounds; Surveys and Questionnaires

The aim of the present study was to identify demographic and treatment factors that were predictive of hypoglycemia in a large cohort of type 2 diabetic patients initiating insulin detemir.. The present 24-week observational study of insulin initiation included 17 374 participants from 10 countries. Severe hypoglycemia was defined as an event requiring third party assistance; minor hypoglycemia was defined as a daytime or nocturnal glucose measurement <3.1 mmol/L.. Prior to initiating insulin therapy, 4.9% of the cohort reported hypoglycemia (pre-insulin hypoglycemia), with most (94.2%) reporting minor events and 9.6% reporting severe events. Compared with patients without pre-insulin hypoglycemia, those with pre-insulin hypoglycemia had a higher incidence of events of minor hypoglycemia (1.72 vs 4.46 events per patient-year [ppy], respectively), nocturnal hypoglycemia (0.25 vs 1.09 events ppy, respectively), and severe hypoglycemia (<0.01 vs 0.04 events ppy, respectively) at final visit. Age (P < 0.047), body mass index (P < 0.001), a prior history of microvascular disease (P < 0.001), pre-insulin hypoglycemia (P < 0.001), increased number of oral hypoglycemic agents (OHAs; P < 0.001), OHA intensification (P < 0.001), and the use of glinides (P = 0.004) were all found to be independently associated with the occurrence of hypoglycemia during the study.. Once-daily insulin detemir therapy was safe and effective, and rates of hypoglycemia were low. Concerns about hypoglycemia should not deter the initiation of basal insulin analogs.

Topics: Administration, Oral; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged; Multivariate Analysis; Prospective Studies; Regression Analysis; Risk Assessment; Risk Factors; Treatment Outcome

It was the aim of this study to assess baseline predictors for glycosylated hemoglobin (HbA1c) reduction, treatment-to-target, and insulin glargine dose in patients with an HbA1c level of ≥ 7.5% (58 mmol/mol) at baseline despite 3 months of maximum tolerated dose of metformin under daily conditions.. This was an open, multicenter, prospective observational study with a 6-month follow-up including 1,438 patients with type 2 diabetes. Baseline variables independently associated with HbA1c (overall reduction and achievement of target values) and insulin glargine dose used were determined using a stepwise multivariate linear regression analysis.. In a multivariate linear regression analysis (R(2)=0.545) baseline HbA1c (β=-0.722; P<0.001) and retinopathy (β=-0.064; P=0.007) were associated with a greater HbA1c reduction at 6 months, whereas duration of diabetes was associated with a lesser HbA1c reduction (β=0.084; P<0.001). In another multivariate linear regression analysis, weight (odds ratio [OR] 0.99; 95% confidence interval [CI] 0.98 to <1.00), duration of diabetes (OR 0.96; 95% CI 0.93-0.99), and baseline HbA1c (OR 0.65; 95% CI 0.56-0.76) were associated with a reduced likelihood of achieving an HbA1c level of <7% (53 mmol/mol); baseline HbA1c (OR 0.66; 95% CI 0.51-0.85) was the only variable associated with a reduced likelihood of achieving an HbA1c level of <6.5% (48 mmol/mol). In a further analysis (R(2)=0.135) the insulin dose needed was increased in those with a higher body weight (β=0.230; P<0.001), a longer duration of diabetes (β=0.134; P<0.001), a higher baseline HbA1c level (β=0.205; P<0.001), and the presence of microalbuminuria (β=0.096; P=0.003).. Identified predictors of greater HbA1c reduction, target goal achievement, and insulin dose needed may help to optimize the balance of benefits and risks with the use of insulin glargine.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Maximum Tolerated Dose; Metformin; Predictive Value of Tests; Prospective Studies; Treatment Outcome

There are a dearth of studies comparing laparoscopic sleeve gastrectomy (LSG) and intensive medical treatment (IMT) in obese type 2 diabetes mellitus (T2DM) patients. This study compares these modalities in terms of weight loss, metabolic parameters and quality of life (QOL) score.. We evaluated the efficacy of LSG (n = 14) vs. IMT (n = 17) comprising of low calorie diet, exenatide, metformin and if required insulin detemir in 31 obese T2DM patients with BMI of 37.9 ± 5.3kg/m(2) and target HbA1c < 7 %. The mean (±SD) age of the patients was 49.6 ± 11.9 years and 74 % were women. The mean duration of diabetes was 8.5 ± 6.1 years and mean HbA1c was 8.6 ± 1.3 %. Primary end point was excess body weight loss (EBWL) at the final follow-up.. The mean duration of follow-up was 12.5 ± 5.0 (median 12) months. EBWL was 61.2 ± 17.6 % and 27.4 ± 23.6 % in LSG and IMT group respectively (p < 0.001). Glycemic outcomes improved in both with mean HbA1c of 6.6 ± 1.5 % in LSG and 7.1 ± 1.2 % in IMT group. In LSG group, there was resolution of diabetes and hypertension in 36 and 29 % of patients respectively while none in the IMT group. HOMA-IR, hsCRP, ghrelin and leptin decreased while adiponectin increased significantly in LSG compared to IMT group. QOL score improved in LSG as compared to IMT.. In obese T2DM patients, LSG is superior to IMT in terms of weight loss, resolution of comorbidities and QOL score.

Topics: Adult; Aged; Comorbidity; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Exenatide; Female; Gastrectomy; Humans; Hypertension; Hypoglycemic Agents; Insulin Detemir; Insulin, Long-Acting; Laparoscopy; Male; Metformin; Middle Aged; Peptides; Quality of Life; Treatment Outcome; Venoms; Young Adult

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

Type-2 diabetes mellitus (T2DM) is a progressive disease, and many patients eventually require insulin therapy. This study examined real-world outcomes of switching basal insulin analogs among patients with T2DM.. Using two large United States administrative claims databases (IMPACT(®) and Humana(®)), this longitudinal retrospective study examined two cohorts of adult patients with T2DM. Previously on insulin glargine, Cohort 1 either continued insulin glargine (GLA-C) or switched to insulin detemir (DET-S), while Cohort 2 was previously on insulin detemir, and either continued insulin detemir (DET-C) or switched to insulin glargine (GLA-S). One-year follow-up treatment persistence and adherence, glycated hemoglobin (HbA1c), hypoglycemia events, healthcare utilization and costs were assessed. Selection bias was minimized by propensity score matching between treatment groups within each cohort.. A total of 5,921 patients (mean age 60 years, female 50.0%, HbA1c 8.6%) were included in the analysis (Cohort 1: IMPACT(®): n = 536 DET-S matched to n = 2,668 GLA-C; Humana(®): n = 256 DET-S matched to n = 1,262 GLA-C; Cohort 2: n = 419 GLA-S matched to n = 780 DET-C), with similar baseline characteristics between treatment groups in each cohort. During 1-year follow-up, in Cohort 1, DET-S patients, when compared with GLA-C patients, had lower treatment persistence/adherence with 33-40% restarting insulin glargine, higher rapid-acting insulin use, worse HbA1c outcomes, significantly higher diabetes drug costs, and similar hypoglycemia rates, health care utilization and total costs. However, in Cohort 2 overall opposite outcomes were observed and only 19.8% GLA-S patients restarted insulin detemir.. This study showed contrasting clinical and economic outcomes when patients with T2DM switched basal insulin analogs, with worse outcomes observed for patients switching from insulin glargine to insulin detemir and improved outcomes when switching from insulin detemir to insulin glargine. Further investigation into the therapeutic interchangeability of insulin glargine and insulin detemir in the real-world setting is needed.

Topics: Adult; Aged; Costs and Cost Analysis; Databases, Factual; Diabetes Mellitus, Type 2; Drug Substitution; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Longitudinal Studies; Male; Middle Aged; Outcome Assessment, Health Care; Retrospective Studies; United States

The purpose of this analysis is to evaluate the safety and effectiveness of insulin initiation with once-daily insulin detemir (IDet) or insulin glargine (IGlar) in real-life clinical practice in Turkish patients with type 2 diabetes mellitus (T2DM).. This was a 24-week multinational observational study of insulin initiation in patients with T2DM.. The Turkish cohort (n = 2886) included 2395 patients treated with IDet and 491 with IGlar. The change in glycosylated haemoglobin (HbA1c) from the pre-insulin levels was -2.21% [95% confidence interval (CI) -2.32, -2.09] in the IDet group and -1.88% [95% CI -2.17, -1.59] in the IGlar group at the final visit. The incidence rate of minor hypoglycaemia increased in both groups from the pre-insulin to the final visit (+0.66 and +2.23 events per patient year in the IDet and IGlar groups, respectively). Weight change in the IDet group was -0.23 kg [95% CI -0.49, 0.02 kg], and +1.55 kg [95% CI 1.11, 2.00 kg] in the IGlar group. Regression analysis with adjustment for previously identified confounders (age, gender, duration of diabetes, body mass index, previous history of hypoglycaemia, microvascular disease, number and change in oral anti-diabetic drug therapy, HbA1c at baseline and insulin dose) identified an independent effect of insulin type (IDet versus IGlar) with a risk of at least one episode of hypoglycaemia (odds ratio (OR): 0.33 [95% CI 0.21, 0.52], p <0.0001), and weight loss ≥1 kg (OR: 1.75 [95% CI 1.18, 2.59], p = 0.005), but not on HbA1c (+0.05% [95% CI -0.15, 0.25%], p = 0.6).. Initiation of basal insulin analogues, IDet and IGlar, were associated with clinically significant glycaemic improvements. A lower risk of minor hypoglycaemia and greater odds of weight loss ≥1 kg was observed with IDet compared with IGlar.. NCT00825643 and NCT00740519.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; International Agencies; Male; Middle Aged; Prognosis; Prospective Studies

Several studies suggest benefits of insulin analogues detemir or glulisine in overweight and obese patients with type 2 diabetes. The present multicentre study therefore examines, whether these insulin analogues are used more frequently in patients with increased body mass index.. Data of 38 560 adult type 2 diabetic patients using insulin analogues, from 150 centres in Germany, registered in a standardized, prospective, computer-based documentation program (DPV), were included. Patients were classified into body mass index categories according to World Health Organization. Analysis was stratified by 3 time periods. To adjust for confounding effects, multivariable logistic regression models were created.. Detemir was preferentially used in overweight (OR 1.36, 95%-CI 1.20-1.53) and obese patients (OR 2.06, 95%-CI 1.84-2.31) compared to normal-weight patients. These effects remained significant after adjusting for sex, age, new/old federal state of Germany, size of centre, treatment in university clinic and clinic/specialized private practice. Models were additionally adjusted for time period and interaction of BMI category with age or sex. For glulisine, a minor effect was present when comparing obese to normal-weight patients (OR 1.26, 95%-CI 1.06-1.50). After adjustment, this finding was no longer significant. Stratified by obesity grade, class III obese patients more frequently used detemir or glulisine compared to class I obese patients. Comparing time periods, odds ratios did not differ, neither for detemir nor for glulisine..  Detemir is used more often in overweight and obese patients compared to normal-weight patients. For glulisine, the relationship is less pronounced.

Topics: Aged; Body Weight; Databases, Factual; Diabetes Mellitus, Type 2; Drug Prescriptions; Female; Germany; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged; Obesity; Overweight; Practice Patterns, Physicians'; Registries

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

Compared with other insulin analogues, insulin detemir induces less weight gain. This study investigated whether this effect was achieved by influencing the hypothalamic appetite regulators neuropeptide Y (NPY) and galanin (GAL).. Type  2 diabetic rat models were established with a high-fat diet and intraperitoneal injection of STZ. All rats were divided into NC, DM, DM+DE and DM+GLA groups. Glycemic levels of all study groups were checked at study onset and after 4 weeks of insulin treatment. Food intake and body weight were monitored during treatment. After 4 weeks, the hypothalamus of rats was examined for NPY and GAL mRNA and protein expression.. After 4 weeks of treatment, compared with the DM+GLA group, the DM+DE group exhibited less food intake (P < 0.05) and less weight gain (P < 0.05), but showed similar glycemic control. The expression of hypothalamic NPY and GAL at both mRNA and protein level were significantly lower (P < 0.05) in the DM+DE group.. Insulin detemir decreased food intake in type 2 diabetic rats, which led to reduced weight gain when compared to insulin glargine treatment. This effect is likely due to downregulation of hypothalamic NPY and GAL.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diet, High-Fat; Eating; Feeding Behavior; Galanin; Hypoglycemic Agents; Hypothalamus; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Neuropeptide Y; Protein Precursors; Rats, Sprague-Dawley; RNA, Messenger; Streptozocin; Weight Gain

In this study, we compared the glucose-lowering effectiveness of insulin analogues and their combination according to baseline glycemic status in patients with type 2 diabetes (T2D) from the A1 chieve(®) study conducted in Korea.. This sub-analysis from the A1 chieve(®) study was a 24-week prospective, multicenter, non-interventional, open-labelled study. Of the 4058 patients, 3074 patients who had their HbA1c level measured at baseline were included in this sub-analysis. We classified patients into three groups according to baseline HbA1c levels: group I (HbA1c  < 7.5%), group II (7.5% ≤ HbA1c  < 9.0%) and group III (HbA1c  ≥ 9.0%).. Patients in group I showed no significant HbA1c reduction with any insulin regimens (detemir, aspart, detemir and aspart or biphasic aspart 30 (Novo Nordisk A/S, DK-2880 Bagsvaerd, Denmark) after 24 weeks of treatment. In group II, although HbA1c was decreased for all insulin regimens, there was no difference in mean HbA1c reduction among the four insulin regimens. In patients with a high baseline HbA1c level (group III), mean HbA1c reduction was the greatest in patients on a basal-bolus regimen (detemir and aspart, -3.50%) and lowest in patients on a bolus regimen (aspart, -1.81%; p < 0.001).. For optimal glycaemic control, a basal-bolus regimen may be adequate for Korean patients with poorly controlled T2D (HbA1c  ≥ 9.0%).

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Prospective Studies

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

To determine the safety and effectiveness of insulin detemir (IDet) in type 2 diabetes patients from the ASEAN cohort of the A1chieve study.. Patients from Indonesia, Malaysia, Philippines and Singapore prescribed IDet at the discretion of their physicians were included. The primary outcome was the incidence of serious adverse drug reactions including major hypoglycaemia over 24 weeks. Secondary endpoints included changes in the frequency of hypoglycaemia, serious adverse events and effectiveness assessments.. This sub-analysis included 1540 patients (insulin-naive, 1239; insulin-experienced, 301) with mean age ± SD 56.4 ± 10.9 years, BMI 25.4 ± 4.6 kg/m(2) and diabetes duration 6.9 ± 5.3 years. Insulin-naive patients received a baseline IDet dose of 0.24 ± 0.11 U/kg titrated up to 0.37 ± 0.21 U/kg by Week 24. The pre-study insulin dose in insulin-experienced patients was 0.41 ± 0.25 U/kg and baseline IDet dose was 0.31 ± 0.24 U/kg titrated up to 0.40 ± 0.20 U/kg by Week 24. Overall hypoglycaemia decreased from 1.73 to 0.46 events/patient-year from baseline to Week 24 (change in proportion of patients affected, p < 0.0001). At Week 24, 1 major hypoglycaemic event was reported in 1 insulin-experienced patient. IDet significantly improved glucose control (p < 0.001) at Week 24. The lipid profile and systolic blood pressure improved (p < 0.001) and body weight did not change significantly. Quality of life was positively impacted (p < 0.001).. IDet was well-tolerated and improved glycaemic control without increasing the risk of hypoglycaemia or weight gain.

Topics: Aged; Asia, Southeastern; Asian People; Biomarkers; Blood Glucose; Blood Pressure; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin, Long-Acting; 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 efficacy of insulin detemir in Indonesian patients with type 2 diabetes (T2D) as a sub-analysis of the 24-week, prospective, multinational, non-interventional A₁chieve study.. This study included 477 Indonesian T2D patients starting insulin detemir at the discretion of their physicians. Safety and efficacy was measured in routine clinical practice at baseline, interim (around 12 weeks from baseline) and final (around 24 weeks from baseline) visit.. At baseline the mean age, duration of diabetes and mean BMI were 55.3 ± 8.5 years, 5.9 ± 4.0 years and 24 ± 3.6 kg/m(2), respectively. Of these patients, 78% were insulin-naive and 22% were prior insulin users. Glycaemic control was poor at baseline. After 24 weeks, significant reductions were observed in mean HbA1c (2.2%, p < 0.001), fasting plasma glucose (90.0 mg/dL, p < 0.001) and postprandial plasma glucose (115.4 mg/dL, p < 0.001) levels, in the entire cohort. Similar significant reductions were also seen in insulin-naive patients and prior insulin users. In the entire cohort, 32.5% patients achieved HbA1c levels <7.0% while 32.0% insulin-naive patients and 33.9% prior insulin users achieved this target after 24 weeks. No hypoglycaemic events were reported in the entire cohort. Modest increase in body weight was noted in the insulin-naive group, while mean body weight decreased in prior insulin users after 24 weeks of insulin detemir therapy.. This sub-analysis suggests that insulin detemir can be a safe and effective option for initiating insulin therapy in people with T2D in Indonesia.

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

Study of Once-daily LeVEmir(®) (SOLVE(TM)) was a 24-week international observational study to evaluate the safety and effectiveness of initiating once-daily insulin detemir (Levemir) as add-on therapy in patients with type 2 diabetes mellitus (T2DM) who failed treatment of oral anti-diabetic drugs (OAD).. The present study was derived from the data of Chinese cohort. A total of 3272 patients with T2DM failing OAD were enrolled in the study. Determir were prescribed to the patients by the decision of the physician. Clinical data were collected at baseline, week 12 and week 24 to evaluate the safety and effectiveness of detemir.. The age of the patients was (56.2 ± 10.8) years with a diabetes duration of (7.1 ± 5.2) years. Their BMI was (25.3 ± 3.3) kg/m(2). No patient experienced any major or nocturnal hypoglycaemic event during the study. After 24 weeks of treatment, the glycosylated hemoglobin A1c (HbA1c) decreased from (8.33 ± 1.69)% to (7.16 ± 1.18)% with a mean change of -1.17%, the fasting plasma glucose decreased from (9.52 ± 2.59) mmol/L to (6.84 ± 1.42) mmol/L with a mean change of -2.7 mmol/L, and the 7-point blood glucose profile improved overall. Totally 49.1% of patients achieved HbA1c < 7%. The mean body weight decreased by 0.15 kg.. Insulin detemir administered once daily as add-on therapy in patients with T2DM failing OAD regimen significantly reduces the risk of major hypoglycemia, improves glycemic control, increases the percentage of patients achieving treatment target with neutral effect on body weight.

Topics: Aged; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged; Prospective Studies; Treatment Outcome

Topics: Aged; Antibodies; Diabetes Complications; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemia; Insulin; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged; Recurrence

Barriers to insulin initiation in type 2 diabetes mellitus (T2DM) include fear of treatment complexity and perceived lack of time and resources by primary care physicians. The SOLVE study investigated the effect of insulin initiation on resource utilisation and patient quality of life.. SOLVE was a 24-week cohort study in 10 countries evaluating the safety and effectiveness of initiating once-daily insulin detemir in patients with T2DM. Patient quality of life was assessed using the Insulin Treatment Appraisal Scale (ITAS).. A total of 14,611 (84%) patients completed the 24-week study. During the study, HbA1c improved by 1.3 ± 1.5%. The corresponding insulin dose increased from 13 ± 6 IU (0.16 ± 0.09 IU/kg) at baseline, to 22 ± 16 IU (0.27 ± 0.17 IU/kg) at final visit. FlexPen was the preferred device (63%) for insulin administration. The time taken to teach patients to self-inject and perform dose self-adjustment was 15 ± 13 min and 11 ± 11 min, respectively. The quality of life analysis included 6875 patients. The addition of insulin was associated with an improvement in mean ITAS score [-3.5 (95% CI -3.8, -3.3), p < 0.001]. Physicians reported the use or self-adjustment of insulin detemir as easy or very easy in 79% of participants; and satisfaction with the level of glycaemic control was reported for 74% of patients.. Initiating basal insulin therapy resulted in a substantial decrease in HbA1c and improved patients' perceptions of insulin treatment.

Topics: Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Health Resources; Humans; Hypoglycemic Agents; Injections, Intradermal; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged; Patient Acceptance of Health Care; Patient Satisfaction; Quality of Life

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Dosage Calculations; Goals; Humans; Insulin Detemir; Insulin, Long-Acting; Titrimetry

Insulin detemir induces bodyweight loss or less weight gain in patients with type 2 diabetes mellitus. However, in contrast to insulin detemir, insulin glargine has no weight loss effect. Increased sodium excretion has been speculated to be one of the mechanisms of weight loss by insulin detemir. However, there are no studies in the literature comparing sodium excretion between patients using insulin detemir and those using insulin glargine. There are also no studies comparing the excretion of urinary albumin and urinary protein in chronic kidney disease (CKD) patients using insulin detemir or insulin glargine. Thus, the aim of the current study was to compare the effects of insulin detemir and insulin glargine on sodium, albumin, and protein excretion in patients with various stages of CKD and concomitant type 2 diabetes.. Demographic, clinical, and laboratory data were evaluated for all patients. Hypoglycemic attacks, appetite score, 24-h urinary sodium, albumin, and protein excretion were also measured.. A total of 47 patients (23 taking insulin detemir, 24 taking insulin glargine) were included in the study. There were no differences with respect to 24-h sodium (p = 0.694), albumin (p = 0.297), or protein excretion (p = 0.202) between patient groups. Appetite and hypoglycemic attacks also did not differ between groups. Use of insulin detemir or insulin glargine was not related to sodium, albumin, and protein excretion in stepwise regression analysis.. There was no difference between insulin detemir and insulin glargine with respect to sodium, albumin, and protein excretion in type 2 diabetic CKD patients. Studies are needed both in CKD patients and those with normal renal function to highlight mechanisms regarding the weight loss effect unique to insulin detemir.

Topics: Aged; Albuminuria; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Proteinuria; Renal Insufficiency, Chronic; Sodium

To determine the safety and effectiveness of insulin analogues in type 2 diabetes (T2D) patients in the Algerian cohort of the A₁chieve study and to examine the status of T2D management across different regions in Algeria.. Patients starting therapy with biphasic insulin aspart 30, insulin detemir, insulin aspart (IAsp) or IAsp + basal insulin at their physicians' decision were included. The primary outcome was the incidence of serious adverse drug reactions (SADRs), including major hypoglycaemia. Secondary outcomes included changes from baseline to Week 24 in hypoglycaemia, glycated haemoglobin A1c (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPPG), weight and quality of life (QoL, evaluated using the EQ-5D questionnaire).. Overall, 1494 patients (mean ± SD age: 60.1 ± 10.3 years; body mass index: 28.1 ± 4.9 kg/m(2); HbA1c: 9.2 ± 1.8%) were enrolled. Poor baseline glucose control was revealed across the different Algerian regions with mean HbA1c varying from 8.9% to 9.6%. Two SADRs were reported during the study. The proportion of patients reporting major hypoglycaemic events decreased from 1.1% at baseline to 0.2% at Week 24 (p = 0.0017). Significant improvements in mean HbA1c (-1.3 ± 2.0%), FPG (-38.8 ± 79.9 mg/dL) and post-breakfast PPPG (-51.4 ± 97.1 mg/dL) were observed in the entire cohort (all p < 0.001). The mean body weight increased by 0.9 ± 3.8 kg, while QoL increased by 9.2 ± 16.7 points after 24 weeks.. Insulin analogue therapy was well-tolerated and significantly improved blood glucose control over 24 weeks in the Algerian cohort.

Topics: Algeria; Biomarkers; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug-Related Side Effects and Adverse Reactions; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged; Postprandial Period; Prevalence; Prospective Studies; Risk Assessment; Risk Factors; Treatment Outcome

To determine the safety and effectiveness of insulin analogues in the Moroccan cohort of the prospective, multinational, non-interventional, 24-week A₁chieve study.. Moroccan patients with type 2 diabetes (T2D) starting biphasic insulin aspart 30, insulin detemir, and insulin aspart alone or in combination were included. The primary outcome was the evaluation of serious adverse drug reactions including major hypoglycaemic events. Secondary outcomes were changes in hypoglycaemic events, glycaemic parameters (HbA1c, fasting plasma glucose [FPG], postprandial plasma glucose [PPPG]), systolic blood pressure (SBP), body weight and lipid profile. Quality of life (QoL) was evaluated using the EQ-5D questionnaire.. In this analysis, 1641 patients (923 insulin-naive, 718 insulin-experienced) having a mean age 57.1 years, mean BMI 26.8 kg/m(2) and mean diabetes duration 10.3 years, were included. Baseline HbA1c in the entire cohort was poor (9.7%, 83 mmol/mol). Insulin analogues statistically significantly improved glucose control (HbA1c, FPG and PPPG, p < 0.001) at Week 24. The rate of hypoglycaemia decreased from 9.31 to 4.71 events/patient-year (change in proportion of patients affected, p = 0.0002). A statistically significant improvement in lipid parameters (except HDL cholesterol) was observed while body weight changed minimally. Additionally, QoL was positively impacted (mean change in visual analogue scores from EQ-5D was 15.8 points, p < 0.001).. Insulin analogue therapy resulted in improved glycaemic control and a significant overall decrease in hypoglycaemia in Moroccan T2D patients.

Topics: Biomarkers; Blood Glucose; Blood Pressure; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged; Morocco; Postprandial Period; Prevalence; Prospective Studies; Quality of Life; Risk Factors; Treatment Outcome; Weight Gain

To evaluate the safety and effectiveness of insulin analogues in patients with type 2 diabetes (T2D) from Morocco, Algeria and Tunisia that formed the Maghrebian cohort of the 24-week, non-interventional A₁chieve study.. Patients starting biphasic insulin aspart, insulin detemir and insulin aspart, alone or in combination, were included. The primary outcome was the incidence of serious adverse drug reactions (SADRs), including major hypoglycaemic events. Secondary outcomes included hypoglycaemia, glycated haemoglobin A₁c (HbA₁c), fasting plasma glucose (FPG), postprandial plasma glucose (PPPG), systolic blood pressure (SBP), body weight and lipids. Quality of life (QoL) was evaluated using the EQ-5D questionnaire.. Overall, 3720 patients with a mean age of 58.6 years, body mass index of 27.7 kg/m(2) and diabetes duration of 11.5 years were enrolled. Pre-study, insulin-experienced patients had a mean ± SD dose of 0.54 ± 0.27 U/kg. In the entire cohort, the mean dose was 0.42 ± 0.27 U/kg at baseline, titrated to 0.55 ± 0.30 U/kg by Week 24. Twenty-six SADRs were reported during the study. There was a significant decrease in the proportion of patients reporting overall hypoglycaemia from baseline to Week 24 (18.3% to 13.8%, p < 0.0001). The mean HbA₁c improved significantly from 9.5 ± 1.8% to 7.9 ± 1.4% (p < 0.001). The mean FPG, PPPG, SBP, total cholesterol and QoL also improved significantly (all p < 0.001), while the mean body weight increased by 0.9 ± 3.9 kg (p < 0.001).. Insulin analogue therapy was well-tolerated and was associated with improved glycaemic control.

Topics: Algeria; Asian People; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin Detemir; Insulin, Long-Acting; Lipids; Male; Middle Aged; Morocco; Postprandial Period; Prospective Studies; Quality of Life; Risk Factors; Surveys and Questionnaires; Treatment Outcome; Tunisia; 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

Basal-bolus insulin regime is frequently used in type 2 diabetes in order to improve metabolic control and decrease the risk of complications. A general question is, however, the effect of application of analogue insulin in comparison to human insulin regimes.. The aim of the authors was to perform a retrospective database analysis among patients who were switched from human insulin only based basal-bolus regime to analogue only insulin regime in order to examine changes in metabolic control, body weight, insulin dose and basal:bolus insulin ratio.. Type 2 diabetic patients (n = 137) were enrolled who used once daily basal insulin with complementary bolus insulin given at main meals, and human insulin was switched to analogue insulin. Patients were divided into two groups using detemir (n = 103) or glargine (n = 34).. During 17 months of analogue insulin treatment the HbA1c was decreased by 0.34% (detemir -0.44%; glargine -0.17%). Body weight was increased by 1.11 kg (detemir +1.0 kg; glargine +1.43 kg). The basal:bolus insulin ratio increased in all groups (entire cohort 6.04%, detemir 5.26%, glargine 8.37%). The average insulin dose was 80.76 units at the end of follow up. There was no significant difference in terms of total and basal insulin doses between detemir (27.89 and 79.78 U, respectively) and glargine group (32.85 and 83.74 U, respectively).. These results support that switching from human to analogue insulin in basal-bolus regime could improve the metabolic control by increasing dose of basal analogue insulin and basal: bolus ratio. Both detemir and glargine can provide similar improvement in metabolic control with the same insulin dose but with relatively more weight gain with glargine.. Bevezetés: 2-es típusú cukorbetegségben egyre gyakrabban kerül alkalmazásra a bázis-bolus inzulinkezelési rendszer, az anyagcserekontroll javítása és a szövődmények kockázatának csökkentése érdekében. Napjaink kérdése, hogy az inzulinanalógok alkalmazása milyen gyakorlati változásokat hoz a humán inzulinkezelési rendszerekhez képest. Célkitűzés: A szerzők retrospektív adatelemzéssel vizsgálták a teljes humán bázis-bolus kezelésről teljes inzulinanalóg-kezelésre váltás hatásait az anyagcserehelyzetre, a testsúlyra, az inzulindózisokra és a bázis-bolus inzulin arányra. Módszer: Olyan 2-es típusú cukorbetegeket (n = 137) vontak be a vizsgálatba, akik napi egyszeri bázisinzulint használtak a főétkezésekhez adott gyors hatású inzulinok mellett, és a humán inzulinokról analóg inzulinokra cserélték a gyógyszerüket. A betegeket detemirt (n = 103) és glargint (n = 34) használó csoportokba sorolták. Eredmények: Tizenhét hónapos inzulinanalóg-terápia során a HbA1c 0,34%-kal csökkent (detemir: –0,44%; glargin: –0,17%). A testsúly 1,11 kg-mal növekedett (detemir: +1,0 kg; glargin: +1,43 kg). A bázisinzulin aránya minden esetben emelkedett (teljes populáció: 6,04%, detemir: 5,26%, glargin: 8,37%). Az átlagos inzulindózis a vizsgálat végén 80,76 egység volt, és nem volt szignifikáns különbség sem a bázis-, sem a teljes inzulindózisokat illetően a detemir- (27,89 E, illetve 79,78 E) és a glargin- (32,85 E, 83,74 E) csoportok között. Következtetések: Az adatok alátámasztják, hogy a humánról analóg inzulinra történő váltáskor, bázis-bolus kezelési rendszerben a bázisinzulin dózisának emelésével, a bázis/bolus arány növelésével javítható az anyagcserekontroll. A detemir- és glarginalapú terápia hasonló anyagcserekontroll-javulás mellett azonos inzulindózisokkal járt, és valamelyest több testsúlynövekedéssel a glargincsoportban. Orv. Hetil., 2013, 154, 1476–1484.

Topics: Adult; Aged; Biomarkers; Databases, Factual; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Weight Gain

The RESOLUTE was a multinational, non interventional, 6 month prospective observational project evaluating in clinical practice, whether patients with type 2 diabetes mellitus (T2DM) inadequately controlled with detemir in combination with oral antidiabetic drugs (OADs) may benefit from switching to glargine. In Czech Republic 200 patients, for whom the participating physician according to their own consideration, had decided to prescribe insulin glargine in replacement of insulin detemir, were included in this project.. The primary endpoint was to assess the change in HbA1c over the 6- month period in T2DM patients treated with insulin glargin after switch from insulin detemir. Secondary endpoints included the evaluation of the change in fasting plasma glucose, insulin dose, body weight over the 6-month period after starting insulin glargine , the evaluation of the number of hypoglycemia during the last month of therapy which each basal insulin and the frequency of adverse events (AE) during treatment with insulin glargine.. Insulin glargine therapy resulted in a statistically significant improvement in compensation of diabetes characterized by a mean HbA1c decrease of about 0.82 (± 0.93) % (p < 0.001) and a mean decrease of recorded fasting glycemia about 1.91 (± 2.81) mmol/ l (p < 0.001). No significant change in the mean body weight was recorded du-ring study [+0.12 (± 2.98) kg; p = NS]. The mean daily insulin glargine dose used at the end of the observation increased in comparison with last mean daily dose of insulin detemir [+2.99 (± 7.54) U; p < 0.001]. The improvement in glycemic control was accompanied by low risk of hypoglycemia. The percentage of patients with documented symptomatic (5.0%), nocturnal (2.5%) and severe (0%) hypoglycemia in the last month of glargine therapy was consistently lower compared with the last month of previous treatment with detemir (14.6%, 9.5% and 2.5%, respectively). Other adverse events were reported in 3.0% of patients on glargine therapy. No adverse events were considered as adverse event related to insulin glargin treatment. No serious adverse or no serious adverse events leading to treatment discontinuation or death were documented during the course of the study.. Under reallife conditions, switching from insulin detemir to once daily insulin glargine in poorly controlled T2DM patients resulted in clinically relevant improvements in glycemic control without an increase in weight and hypoglycemia risk.

Topics: Aged; Aged, 80 and over; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Substitution; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Prospective Studies

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

This subgroup analysis of the A₁chieve study examined data from 15,545 people who started treatment with insulin detemir ± oral glucose-lowering drugs in routine clinical care.. A₁chieve was a 24-week, international, prospective, non-interventional study of people with type 2 diabetes from non-Western nations starting treatment with basal insulin detemir, bolus insulin aspart or biphasic insulin aspart 30, alone or in combination, to evaluate their safety and effectiveness in routine clinical practice.. HbA₁c for the global cohort improved after 24 weeks from 9.5 ± 1.6% by -2.0 ± 1.6% [80 ± 17 by -22 ± 17 mmol/mol] (-2.1 ± 1.6% [-23 ± 17 mmol/mol] for insulin-naïve participants; -1.6 ± 1.7% [-17 ± 19 mmol/mol] for prior insulin users). Fasting plasma glucose and postprandial plasma glucose were also significantly reduced (p<0.001), irrespective of prior therapy or geographical region. The incidence of major hypoglycaemia decreased significantly over 24 weeks in both the insulin-naïve and insulin-experienced groups (p<0.0001). Mean body weight decreased overall by -0.4 ± 4.0 kg and blood pressure, lipid profiles, and self-reported quality of life improved over 24 weeks for all people starting treatment with insulin detemir.. People with type 2 diabetes in poor glycaemic control starting treatment with insulin detemir reported significant improvements in glycaemic control with improved treatment tolerability, irrespective of prior treatment and geographical region, after 24 weeks.

Topics: Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged; Prospective Studies; Treatment Outcome

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

Insulin aspart (IAsp) has been used in patients for more than a decade. A plethora of data is available, from clinical trials, to document its efficacy and safety and suggest that IAsp is a favorable choice to be used in a basal-bolus regimen. The A1chieve@ was a non-interventional study that explored the safety and effectiveness of initiating or switching to insulin analogues in routine clinical practice in more than 60,000 patients from 28 different countries. In this manuscript, we discuss the findings from the subgroup of the Indian cohort who were treated with insulin aspart (IAsp), in addition to a basal insulin analogue (insulin detemir, IDet). In a cohort of 343, who were on IAsp + IDet, 175 (51%) were insulin naive and 168 (49%) had been on insulin therapy earlier. Glycaemic parameters were high at baseline. Mean HbA1c was 9.3% in them and was comparable in both insulin naive and insulin experienced groups. After 24 weeks of therapy with IAsp + basal insulin, there were reductions in HbA1c in both the insulin naive group, (-1.6) and insulin experienced group (-1.5). Fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) levels were also reduced significantly from baseline (-77 and - 110 mg/dL, respectively, p < 0.001). Overall, hypoglycaemia decreased from 0.97 (baseline) to 0.18 events/patient years (24 weeks). There was also an increase in quality of life score as evaluated by EQ-5D questionnaire. Addition of IAsp with a basal insulin in patients with poor glycaemic control leads to an improvement in glycaemic profile with no major hypoglycaemia or clinically significant weight gain along with an improvement in the quality of life in patients with type 2 diabetes.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; India; Insulin Aspart; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged; Prospective Studies; Quality of Life

To determine the effects on quality of life after starting insulin with, or switching to, insulin analogue therapies in Indians with type 2 diabetes mellitus in the 24-week, prospective, observational A1chieve study.. Health-related quality of life (HRQoL) was assessed at baseline and at 24 weeks by the validated EQ-5D questionnaire (visual analogue score [VAS] and five dimensions) in 20,554 people who had started using basal insulin detemir, mealtime insulin aspart (with or without a basal insulin) or biphasic insulin aspart 30.. Quality of life improved in both insulin-naive and insulin experienced patients in all treatment groups. At the start of the study, 63.2% of the insulin-naive patients reported problems with walking but after 24 weeks, only 15.2% reported difficulties. At baseline all HrQOL parameters were deteriorated in Indian cohort and the improvement observed was highly significant and well appreciated. The improvement was seen across all insulin regimen and all regions around India.. Compared with baseline scores, HRQoL improvement was seen after 24 weeks of treatment with all insulin analogue therapies

Topics: Activities of Daily Living; Adult; Aged; Anxiety; Biphasic Insulins; Depression; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; India; Insulin Aspart; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged; Prospective Studies; Quality of Life; Walking

The A1chieve study evaluated safety and effectiveness of insulin analogues in a large and diverse population. This report presents a subgroup analysis of the A1chieve observational study pertaining to India.. To assess safety and effectiveness of initiation or intensification of insulin detemir in patients with type 2 diabetes mellitus (T2DM) not achieving adequate glycemic control.. The A1chieve study was a prospective, multi-center, open-label, non-interventional study of 24-weeks duration. In this post-hoc analysis, Indian patients with T2DM who did not achieve their glycemic targets, and were started with or switched to insulin detemir, were evaluated at baseline and after 24 weeks of therapy for safety and effectiveness. Adverse events (AE) noted during the course of therapy were recorded. Additionally Glycemic, non-glycemic parameters and quality of life indices were reported. Appropriate statistical analysis was carried out to assess the statistical significance.. The Indian cohort of 2707 patients with T2DM treated with insulin detemir included 2336 (86.29%) insulin-naive and 371 (13.71%) insulin-experienced patients. No adverse drug reaction (ADR) was noted over 24 weeks, one patient (out of 2707) reported serious adverse event. Major hypoglycemia was reported in 0.5% (0.08 events/patient year) patients and reduced to 0% (0 events/patient year) over 24 weeks. After 24 weeks' treatment with insulin detemir, an overall reduction in HbA(1c) of 2.1% was noted (p < 0.001), with a 2.1% (p < 0.001) and 2% (p < 0.001) reduction in insulin-naive and insulin-experienced groups, respectively. A significant reduction in fasting ([mean +/- SD] -3.8 +/- 2.5 mmol/L) and postprandial (-5.2 +/- 3.9 mmol/L) blood glucose (FPG and PPG) was also observed (p < 0.001 for both). At end of the study, 24.4% patients achieved the ADA target of < 7.0% and 14.3% patients achieved the AACE target of < 6.5% for HbA(1c). A significant improvement in quality of life indices like ED-5D (0.31 +/- 0.29; p < 0.001) and EQ-VAS (21.7 +/- 16.7; p < 0.001) was noticed.. In patients with T2DM not achieving their glycemic targets addition of basal insulin detemir was well tolerated and reported improvement in glycemic control.

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

We analyzed the impact of the removal of administrative restrictions on basal analog insulin prescribing by primary care physicians in the year 2008 in a large HMO.. This cross-sectional database study of patients with diabetes study was conducted in Maccabi Healthcare Services, the second largest HMO in Israel, insuring 1.9 million members countrywide. The research population included men over 40 and women over the age of 45 from MHS diabetes registry during the time period 1.1.2002-31.12.2009.. After removal of basal analog insulin prescription restrictions, more primary care physicians initiated treatment with basal analog insulin than with other types of insulin and did so with fewer referrals for specialty diabetes consultation. No growth in the relative number of patients commencing insulin use was observed, nor did we find an earlier initiation of insulin.. In the first year following the relaxation of prescribing restrictions on the use of basal analog insulin we observed an increase in its use amongst patients previously treated with other types of insulin. The administrative changes did not result in an overall increase in the use of insulin in the study population.

Topics: Adult; Biomarkers; Chi-Square Distribution; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Drug Prescriptions; Drug Utilization; Drug Utilization Review; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Israel; Male; Middle Aged; Practice Guidelines as Topic; Practice Patterns, Physicians'; Primary Health Care; Registries; Retrospective Studies; Time Factors

Older patients are particularly vulnerable to hypoglycaemia. The aim of this study was to evaluate the response to initiation of once-daily insulin detemir in patients aged ≥75 years with type 2 diabetes mellitus (T2DM) treated with one or more oral antidiabetic drugs (OADs).. A sub-analysis was conducted using data from SOLVE (Study of Once daily LeVEmir), a 24-week observational study involving 3,219 investigators and 2,817 project sites from ten countries. Routine clinical practice was followed; there were no study-prescribed procedures. The total cohort comprised 17,374 participants, of whom 2,398 (14 %) were aged ≥75 years. The physicians collected information from patient recall, the patients' medical records and their self-monitored blood glucose diaries (if kept).. Pre-insulin glycated haemoglobin (HbA(1c)) was similar between participants aged ≥75 years and those aged <75 years (HbA(1c) 8.8 ± 1.5 % vs. 8.9 ± 1.6 % [mean ± SD], respectively). After 24 weeks of treatment, similar reductions in HbA(1c) were observed in the two subgroups: 7.6 ± 1.1 % and 7.5 ± 1.2 % in participants aged ≥75 years and those aged <75 years, respectively. The incidence of severe hypoglycaemia (episodes per patient-year) decreased during the study in both age groups (from 0.057 to 0.007 in patients aged ≥75 years; from 0.042 to 0.005 in patients aged <75 years), while minor hypoglycaemia increased from 1.1 to 2.0 and from 1.7 to 1.8 episodes per patient-year in the older and younger age groups, respectively. Average weight reduction was similar in both groups: -0.5 kg (≥75 years) and -0.6 kg (<75 years).. In both the older and younger age groups, the addition of once-daily insulin detemir to existing OAD regimens was effective and safe. In older patients, an improvement in HbA(1c) of 1.2 % was not associated with an increased risk of severe hypoglycaemia or weight gain.

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

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

The progressive nature of type 2 diabetes necessitates exogenous insulin use for most patients; basal insulin plus oral anti-diabetes drugs (OADs) is a well-validated way to facilitate insulin initiation. The primary aim of this study was to explore insulin initiation strategies and outcomes for patients using insulin detemir or glargine plus oral anti-diabetes drugs.. LIGHT was a 3-month, longitudinal observational study conducted across 761 French centres in insulin-naïve type 2 diabetes patients managed under routine clinical care conditions, in either primary or secondary care. Endpoints included changes in HbA(1c) , fasting plasma glucose (FPG), rate of hypoglycaemia, weight, and adverse events.. Most physicians initiated a basal analogue to improve glycaemic control (97%), with many delaying beginning treatment for several months (9 ± 9.0 months for general practitioners, 10.2 ± 16.2 months for specialists). Most patients continued oral anti-diabetes drug therapy (95%) and lifestyle measures (92%), with 2-3 blood glucose readings per day and follow-up telephone calls for dose optimization. Mean change in HbA(1c) from baseline was - 1.3%, and - 3.1 mmol/L for fasting plasma glucose (both p < 0.0001). Hypoglycaemia increased from 1.4 to 5.6 events/patient/year (p < 0.0001), and weight decreased on average by 0.5 kg with detemir, with no change in glargine. Most patients (93%) reported being satisfied or very satisfied with their insulin.. Insulin initiation with detemir or glargine can be successfully managed in both primary and secondary care; the benefits of basal analogues (once-daily dosing, low rates of hypoglycaemia compared with neutral protamine Hagedorn) may have contributed to patient acceptance of the regimen.

Topics: Aged; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; France; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Life Style; Longitudinal Studies; Male; Middle Aged; Patient Compliance; Treatment Outcome

The aim of this analysis is to determine the timing of insulin initiation in routine clinical practice, especially in relation to glycaemic control and use of oral antidiabetic drugs (OADs).. Study of Once Daily Levemir was a 24-week international observational study involving 10 countries which evaluated the safety and effectiveness of initiating once-daily insulin detemir in people with type 2 diabetes mellitus (T2DM) being treated with one or more OADs (clinical trial number NCT00825643 and NCT00740519).. A total of 17 374 participants were enrolled in the study: aged 62 ± 12 years, 53% male, T2DM duration 10 ± 7 years, body mass index 29.3 ± 5.4 kg/m(2) . Pre-insulin HbA1c was 8.9 ± 1.6%. The proportion of patients with HbA1c ≥9.0% ranged from 64% (UK) to 23% (Poland). Pre-insulin OAD treatment included metformin (81%), sulphonylureas (59%), glinides (16%), thiazolidinediones (TZD) (12%), α-glucosidase inhibitors (12%) and dipeptidyl peptidase (DPP)-IV inhibitors (7%). The mean starting dose of insulin detemir for the total cohort was 0.16 ± 0.09 U/kg. Differences in OAD use and insulin doses at initiation were evident among participating countries. The largest proportional changes in OAD prescribing at insulin initiation were seen with glinides (+15%), sulphonylureas (-19%), TZD (-31%) and DPP-IV inhibitors (-28%).. Despite well-documented benefits of timely glycaemic control and consensus guidelines encouraging earlier use of insulin, considerable clinical inertia exists with respect to initiating appropriate insulin therapy in people with T2DM. Considerable regional differences exist in the timing of insulin initiation and in the use of OADs.

Topics: Administration, Oral; Attitude of Health Personnel; Blood Glucose; Cohort Studies; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Guideline Adherence; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged; Practice Guidelines as Topic; Time Factors

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

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

Insulin therapy using insulin detemir (d-INS) has demonstrated weight-sparing effects compared with other insulin formulations. Mechanisms underlying these effects, however, remain largely unknown. Here we postulate that the intestinal tissues' selective preference allows d-INS to exert enhanced action on proglucagon (Gcg) expression and the production of glucagon-like peptide (GLP)-1, an incretin hormone possessing both glycemia-lowering and weight loss effects. To test this hypothesis, we used obese type 2 diabetic db/db mice and conducted a 14-day intervention with daily injection of a therapeutic dose of d-INS or human insulin (h-INS) in these mice. The body weight of the mice after 14-day daily injection of d-INS (5 IU/kg) was decreased significantly compared with those injected with the same dose of h-INS or saline. The weight-sparing effect of d-INS was associated with significantly elevated circulating levels of total GLP-1 and reduced food intake. Histochemistry analysis demonstrated that d-INS induced rapid phosphorylation of protein kinase B (Akt) in the gut L cells of normal mice. Western blotting showed that d-INS stimulated Akt activation in a more rapid and enhanced fashion in the mouse distal ileum compared with those by h-INS. In vitro investigation in primary fetal rat intestinal cell (FRIC) cultures showed that d-INS increased Gcg mRNA expression as determined by Northern blotting and real-time RT-PCR. Consistent with these in vivo investigations, d-INS significantly increased GLP-1 secretion in FRIC cultures. Consistently, d-INS was also shown to induce rapid phosphorylation of Akt in the clonal gut cell line GLUTag. Furthermore, d-INS increased β-catenin phosphorylation, its nuclear translocation, and enhanced cAMP response element-binding protein (CREB) phosphorylation in a phosphatidylinositol 3-kinase and/or mitogen-activated protein kinase kinase/extracellular signal-regulated kinase-sensitive manner. We suggest that the weight-sparing benefit of d-INS in mice is related to its intestinal tissues preference that leads to profound stimulation of Gcg expression and enhanced GLP-1 secretion in intestinal L cells, potentially involving the activation of insulin/β-catenin/CREB signaling pathways.

Topics: Animals; beta Catenin; Cells, Cultured; Cyclic AMP Response Element-Binding Protein; Diabetes Mellitus, Type 2; Fetus; Gene Expression Regulation; Glucagon-Like Peptide 1; Hypoglycemic Agents; Insulin Detemir; Insulin, Long-Acting; Intestinal Mucosa; L Cells; Mice; Mice, Mutant Strains; Obesity; Organ Specificity; Phosphorylation; Proglucagon; Protein Processing, Post-Translational; Rats; Rats, Wistar; RNA, Messenger

Evaluate the safety and efficacy of once-daily insulin detemir initiated in routine clinical practice in patients with type 2 diabetes mellitus inadequately controlled with oral hypoglycaemic agents (OHAs).. This large observational study was conducted in 10 countries. Adverse event data (including hypoglycaemia) and glycaemic control were recorded before and 24 weeks following insulin initiation while patients continued routine clinical management.. In this study, 17 374 patients (53% male) were included. Mean pre-insulin values (±s.d.) were: age 62 ± 12 years; body mass index (BMI) 29.3 ± 5.4 kg/m(2); diabetes duration 10 ± 7 years; haemoglobin A1c (HbA1c) 8.9 ± 1.6%. During the study, 27 patients experienced serious adverse drug reaction, severe hypoglycaemic events or both; and there were 31 episodes of severe hypoglycaemia in 21 patients. After 24 weeks, HbA1c was 7.5 ± 1.2% (change of -1.3%; p < 0.001) and mean weight change was -0.6 kg (confidence interval -0.7, -0.5 kg, p < 0.001). Daily insulin dose increased from 13 ± 6 U (0.16 ± 0.09 U/kg) to 22 ± 16 U (0.27 ± 0.17U/kg) by 24 weeks. Multivariate regression analysis identified several independent demographic and treatment predictors of end of study HbA1c.. Addition of once-daily insulin detemir to patients with type 2 diabetes mellitus on OHA therapy resulted in few adverse events, significant improvements in glycaemic control, small reductions in weight and low rates of hypoglycaemia. On the basis of this study, concerns about hypoglycaemia or weight gain should not preclude initiation of basal insulin analogues in patients with poor glycaemic control on OHAs.

Topics: Aged; Blood Glucose; Body Mass Index; Canada; China; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Europe; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome

To compare the pharmacokinetic (PK) [area under the curve (AUC₀(-)₂₄ (h), C(max))] and pharmacodynamic (PD) (AUC(GIR) ₀(-)₂₄ (h), GIR(max)) properties of single-dose insulin detemir in the presence or absence of steady-state liraglutide (1.8 mg dose) in subjects with type 2 diabetes to determine whether co-administration affected the PK and PD profiles of either therapeutic agent.. Following a 3-week washout of oral antidiabetic agents (OADs) other than metformin, PK and PD assessments during three euglycaemia clamps were conducted: day 1 following a single dose of insulin detemir alone (0.5 U/kg), day 22 after 3 weeks of once-daily liraglutide with weekly dose escalation to 1.8 mg daily, and day 36 after 2 weeks of steady-state liraglutide maintenance at the 1.8 mg dose following co-administration with a single dose of insulin detemir (0.5 U/kg).. The study population (N = 33; age 49.6 (±8.5) years) had diabetes for an average of 6.5 (±4.1) years, BMI 33 (±6.4) kg/m², FPG 9.7 (±1.6) mmol/l and HbA1c 8.3% (±0.9). PK: The PK profiles of insulin detemir were similar with and without steady-state liraglutide. Liraglutide did not affect AUC or C(max) of insulin detemir and vice versa. The 90% confidence intervals (CIs) for ratios of insulin detemir AUC [1.03; CI (0.97, 1.09)] and C(max) [1.05; CI (0.98, 1.13)] and liraglutide AUC [0.97; CI (0.87, 1.08)] and C(max) [1.03, CI (0.93, 1.13)] were all within the no-effect boundary (0.80, 1.25) (bioequivalence criterion). A stable mean insulin detemir concentration with and without liraglutide was maintained at the end of the 24-h PK sampling period. PD: The sum of AUC(GIR) for liraglutide (1982 mg/kg) and insulin detemir (1058 mg/kg) when given alone was similar to that obtained when the two were co-administered (2947 mg/kg). No serious adverse events were reported and no adverse events led to study withdrawal.. Co-administration of liraglutide 1.8 mg at steady state and insulin detemir produces an additive glucose-lowering effect without affecting the PK profile of either therapeutic agent suggesting that the addition of insulin detemir to patients treated with liraglutide will not require titration algorithms different from when insulin is added to OADs. The co-administration of insulin detemir and liraglutide was well tolerated.

Topics: Area Under Curve; Diabetes Mellitus, Type 2; Drug Interactions; Drug Therapy, Combination; Female; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Liraglutide; Male; Middle Aged; Treatment Outcome

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

We investigated whether differences in duration of first insulin use in type 2 diabetes remain after adjustment for potential confounders, and what factors are associated with longer use.. People prescribed a first insulin (2000-2007) after 2-3 non-insulin glucose lowering treatments (OGLD) were identified from the THIN UK primary care database and grouped by insulin, detemir (n=165), glargine (n=1011) or NPH (n=420). Time from beginning insulin to the prescription of another insulin type or a glucagon-like peptide was compared between insulins in a Cox model adjusting for: demographics, HbA1c, history of vascular complications and cardiovascular risk factors. The strength of association between duration of use and these variables was investigated.. The adjusted hazard ratios compared to glargine for treatment change were 1.58 (95% CI 1.25, 2.00) for detemir and 1.49 (1.25, 1.78) for NPH. Lower mean treatment HbA(1c) correlated with longer time to a different insulin regimen (Spearman rank correlation -0.30, p<0.01) as were continuing OGLDs, older age, longer time from diagnosis, lower body mass index, lower HbA(1c), and no heart failure at baseline.. People who began treatment with glargine and those with better on-treatment HbA(1c) remained on their first insulin for longer than those who began detemir or NPH.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Female; Glucagon-Like Peptides; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Retrospective Studies; Time Factors

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

The main purpose of this study was to investigate whether treatment with long-acting insulin once a day or short-acting insulin three times before each meal daily has a stronger antioxidative effect in patients with type 2 diabetes. These patients had not been treated previously with insulin and were hospitalized for initiation of glycemic control by insulin injection. The patients (n=43) were assigned consecutively and alternately to a group treated with insulin aspart injection three times daily just before each meal and a group treated with insulin detemir injection once daily before bedtime. The results showed that insulin aspart three times a day produced a greater improvement in plasma glucose, and particularly in mean postprandial plasma glucose, compared with insulin detemir once a day (p = 0.0006 for comparison of changes between the two insulin treatments). The amount of insulin needed to approach the target levels of plasma glucose was larger in the insulin aspart group (26.0 ± 10.7 U/day vs. 13.7 ± 4.9 U/day; p < 0.0001). However, only insulin detemir significantly decreased oxidative stress evaluated based on the level of urinary 8-iso-prostaglandin F2α (p = 0.0079), although the mechanisms are not fully evident.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Dinoprost; Drug Administration Schedule; Female; Humans; Insulin Aspart; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged; Oxidative Stress

Control of diabetes is challenging, and frequent treatment changes are needed.. To study the effect of the recommendation to start insulin glargine or insulin determir (long-acting insulin treatment, LAI) at discharge from hospital, on glucose control in the community setting.. Included were type II diabetes patients who were referred to and received a consultation from the hospital diabetes clinic during their hosptialization, as part of a routine consultation for diabetes management. During the visit, all patients were recommended long-acting insulin-based treatment, as inpatient treatment and at discharge. Follow-up was done by the primary physician in the community or by a community-based diabetes clinic. Glycosylated hemoglobin, glucose levels and other laboratory tests were obtained from the community health records before hospitalization and 6-12 months later. Medical treatment was ascertained by reviewing the actual usage of prescriptions.. Eighty patients (58% males, mean age 64.1 +/- 12.7 years) were included in the analysis. HbA1c levels were 10.1 +/- 2.4% before admission, but improved significantly at follow-up (8.6 +/- 2.2%, P < 0.001). Seventy-one percent of the patients were taking the LAI treatment and the rest were using non-LAI medications. Changes in diabetes control were similar between the LAI and non-LAL groups (HbA1c was reduced by 1.5 +/- 3.2% and 1.9 +/- 3.1% respectively). The rate of repeated admissions was also similar, averaging at 1.3 admissions for both groups, the minority of which were related to glucose control.. Insulin glargine or determir-based treatment does not show any superiority over other anti-diabetes treatment. It is our opinion that this treatment should be used as tailored therapy and should not be recommended routinely to all patients.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome

Real-world data comparing outcomes of type 2 diabetes mellitus (T2DM) patients initiating different insulin regimens can help with treatment decisions and patient management. Clinical and economic outcomes following initiation with insulin glargine disposable pen (GLA-P) or insulin detemir disposable pen (DET-P) in T2DM patients were compared over 1-year follow-up.. This retrospective cohort analysis was conducted on data in a US national managed care claims database (July 2006 to September 2010) from patients initiating insulin treatment with GLA-P or DET-P. Treatment persistence, adherence, glycated hemoglobin (A1C), hypoglycemic events, and healthcare costs during follow-up were compared.. In all, 1682 patients were identified; 1016 (60.4%) started using GLA-P, 666 (39.6%) started using DET-P. After 1:1 propensity score matching, each cohort comprised 640 patients. Patients initiating GLA-P were significantly more likely to persist and adhere to treatment, and used a lower daily consumption dose. Over the last quarter of follow-up, fewer GLA-P users switched to DET-P compared with those switching from DET-P to GLA-P. GLA-P was associated with lower A1C levels and higher reduction of A1C levels from baseline, with no significant difference in the number of patients having hypoglycemic events. Patients in both cohorts had similar total and diabetes-related healthcare costs, but healthcare costs were lower in the GLA-P cohort for each 1% reduction in A1C from baseline.. This real-world study demonstrates that patients initiating GLA-P were more likely to persist with and adhere to treatment, with better glycemic control and similar overall hypoglycemia rate at no increase in healthcare cost.

Topics: Adult; Aged; Cohort Studies; Diabetes Mellitus, Type 2; Disposable Equipment; Drug Dosage Calculations; Drug Monitoring; Female; Glycated Hemoglobin; Health Care Costs; Humans; Hypoglycemia; Hypoglycemic Agents; Injections; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Outcome and Process Assessment, Health Care; Patient Preference; Retrospective Studies

To compare the glycemic variability of insulin detemir and insulin glargine in type 1 and type 2 diabetic patients.. 15 type 1 and 14 type 2 diabetic patients receiving intensive insulin therapy with insulin glargine were enrolled. Before and after switching insulin glargine to insulin detemir, we assessed fasting glucose variability using the standard deviation (SD) and the coefficient of variance (CV) of self-monitored fasting blood sugar (FBS) levels.. The SD and CV values were significantly decreased in type 1 diabetes after switching the therapy, though there was no significant difference in type 2 diabetes. The frequency of hypoglycemia was decreased in type 1 diabetes and there was no change in type 2 diabetes. The changes of the CV value also showed significant positive correlation with fasting serum CPR levels in all patients and total insulin dose in type 1 diabetes. The changes of frequency of hypoglycemia showed significant positive correlation with total and basal insulin dose adjusted for body weight in type 1 diabetes.. The present study demonstrated lower within-subject variability of insulin detemir compared to insulin glargine, suggesting that the basal insulin replacement with insulin detemir may provide a useful therapeutic strategy for uncontrolled type 1 diabetes with high glucose variability.

Topics: Adult; Aged; Blood Glucose; Blood Pressure; C-Peptide; C-Reactive Protein; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Insulin, Regular, Pork; Male; Middle Aged; Reproducibility of Results

A one-year cost analysis comparing basal insulin analogues glargine (IG, Lantus) versus detemir (ID, Levemir) in combination with oral antidiabetic drugs (basal supported oral therapy; BOT) in insulin naive Type 2 diabetes patients in Germany based on the results of a randomized controlled clinical trial (RCT). The trial demonstrated equivalent treatment efficacy.. Total direct diabetes treatment costs were estimated from the perspective of the German statutory health insurance (SHI) for the time horizon of one-year. Simulated resources included medication (insulin, oral antidiabetic drugs) and consumable items (needles, blood glucose test strips and lancets). Initial and final insulin doses per kg body weight and proportion of patients with once/twice daily insulin injection were taken from the above mentioned RCT. Unit costs were taken from official German price lists and sources. Deterministic-(DTA) and probabilistic sensitivity analyses (PSA) on resource use and unit costs were performed to test robustness of the results.. Average annual treatment costs per patient (base case) were euro 849 for glargine and euro 1,334 for detemir resulting in cost savings of euro 486 per patient per year (36%). Costs of insulins were euro 469 (IG) and euro 746 (ID). Costs of consumable items amounted at euro 380 (IG) and euro 588 (ID) respectively. Sensitivity analyses confirmed the findings in favor of insulin glargine. PSA results found cost savings ranging from euro 429 to euro 608 (5th/95th percentiles).. The current model estimated that insulin glargine was associated with lower annual treatment costs of euro 486 (36%) compared to the use of insulin detemir while the same glycemic control is expected to be achieved.

Topics: Adult; Diabetes Mellitus, Type 2; Germany; Health Care Costs; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Randomized Controlled Trials as Topic; Reagent Strips; Syringes

Current guidelines for the management of type 2 diabetes call for the use of basal insulin when glycemic targets are not achieved. Previous studies have demonstrated noninferiority of insulin detemir, dosed once or twice daily, and insulin glargine, dosed once daily. In this issue of Journal of Diabetes Science and Technology, Dr. Allen King provides additional data of his previously published randomized, double-blinded, crossover trial in which both insulins were restricted to once-daily use. In this trial of 29 patients, 24-hour continuous glucose monitoring profiles (published previously) and dosing requirements (in this publication) were shown to be statistically equivalent between the two insulins. The shortcomings of this trial are its short duration, small number of patients, and potential interference from endogenous insulin. Longer trials with more patients, studying once-daily use of these medications, will help better determine if any significant differences exist.

Topics: Blood Glucose; Circadian Rhythm; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Dosage Calculations; Evidence-Based Medicine; Humans; Hypoglycemic Agents; Individuality; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Randomized Controlled Trials as Topic; Therapeutic Equivalency

Insulin detemir provides prolonged, reproducible blood glucose reduction through a mechanism unique among basal insulins. It was originally studied clinically in predominantly basal + bolus regimens and found to be associated with a low risk of hypoglycaemia compared to insulin NPH, and reduced weight gain compared to other basal insulins. Insulin detemir has been increasingly studied in basal-only insulin regimens in type 2 diabetes, in which an understanding of how to optimize its use has been built incrementally. Glycaemic control and limitation of weight gain tend to be maximized by once-daily (evening) dosing, earlier initiation and careful titration to appropriate fasting glucose targets.

Topics: Diabetes Mellitus, Type 2; History, 20th Century; History, 21st Century; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting

The objective was to compare glycemic control, insulin utilization, and body weight in patients with type 2 diabetes (T2D) initiated on insulin detemir (IDet) or insulin glargine (IGlar) in a real-life setting in the Netherlands.. Insulin-naïve patients with T2D, starting treatment with IDet or IGlar between January 1, 2004 and June 30, 2008, were selected from the PHARMO data network. Glycemic control (hemoglobin A1c [HbA1c]), target rates (HbA1c <7%), daily insulin dose, and weight gain were analyzed comparing IDet and IGlar for patients with available HbA1c levels both at baseline and at 1-year follow-up. Analysis of all eligible patients (AEP) and a subgroup of patients without treatment changes (WOTC) in the follow-up period were adjusted for patient characteristics, propensity scores, and baseline HbA1c.. A total of 127 IDet users and 292 IGlar users were included in the WOTC analyses. The mean HbA1c dropped from 8.4%-8.6% at baseline to 7.4% after 1 year. Patients at HbA1c goal increased from 9% at baseline to 32% for IDet and 11% to 35% for IGlar, which was not significantly different (OR 0.75, 95% CI 0.46, 1.24). Weight gain (n=90) was less among IDet users (+0.4 kg) than among IGlar users (+1.1 kg), albeit not significant. The AEP analysis (252 IDet + 468 IGlar users) showed similar results with 33%-36% at goal (OR 0.81, 95% CI 0.57, 1.16), and median daily insulin doses of 25 IU/day (P=0.70).. There was no significant difference between users of IDet and IGlar with respect to glycemic control and insulin dose in a real-life setting. The low proportion of patients on target at baseline may indicate that insulin therapy is initiated too late. Moreover, the observation that one-third of the patients reached HbA1c target at follow-up may indicate that basal insulin analogs are not titrated intensively enough.

Topics: Aged; Body Weight; Cohort Studies; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Drug Utilization; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Insurance Claim Review; Male; Middle Aged; Retrospective Studies

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

Topics: Clinical Trials as Topic; Diabetes Mellitus, Type 2; Drug Administration Schedule; Humans; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Treatment Outcome

To compare the properties of insulin detemir with human insulin or insulin aspart in various in vitro and in vivo experiments, thereby highlighting the importance of performing dose-response studies when investigating insulin analogues, in this study specifically insulin detemir.. Displacement of membrane-associated insulin receptors from human and rat hepatocytes, and from Chinese Hamster Ovary cells over-expressing human insulin receptor (CHO-hIR) at varying albumin concentrations is measured. Lipogenesis in primary rat adipocytes over time and the effects in the simultaneous presence of insulin detemir and human insulin or insulin aspart are assessed. The hyperinsulinaemic euglycaemic clamp technique in rats is used to establish dose-response curves for multiple metabolic endpoints and to investigate the effects of the simultaneous presence of insulin detemir and human insulin.. Both in vitro and in vivo, insulin detemir shows full efficacy and right-shifted parallel dose-response curves compared with human insulin. The potency estimates are different between the in vivo and in vitro conditions and among different in vitro conditions, that is the potency decreases in vitro with increasing albumin concentration. The effects of insulin detemir and human insulin are additive both in vitro and in vivo.. Insulin detemir is fully efficacious compared with human insulin on all metabolic endpoints measured in vitro and in vivo. The fact that the potency estimates are method-dependent emphasizes the importance of establishing full dose-response relationships when characterizing insulin detemir.

Topics: Animals; CHO Cells; Cricetinae; Cricetulus; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin, Long-Acting; Lipids; Male; Rats; Rats, Sprague-Dawley; Receptor, Insulin

To compare the treatment costs of insulin glargine (IG; Lantus) to detemir (ID; Levemir), both combined with bolus insulin aspart (NovoRapid) in type 2 diabetes (T2D) in Germany.. Cost comparison was based on data of a 1-year randomised controlled trial. IG was administered once daily and ID once (57% of patients) or twice daily (43%) according to treatment response. At the end of the trial, mean daily basal insulin doses were 0.59 U/kg (IG) and 0.82 U/kg (ID). Aspart doses were 0.32 U/kg (IG) and 0.36 U/kg (ID). Costs were calculated from the German statutory health insurance (SHI) perspective using official 2008 prices. Sensitivity analyses were performed to test robustness of the results.. Annual basal and bolus insulin costs per patient were euro 1,473 (IG) and euro 1,940 (ID). The cost of lancets and blood glucose test strips were euro 1,125 (IG) and euro 1,286 (ID). Annual costs for needles were euro 393 (IG) and euro 449 (ID). The total annual cost per patient of administering IG was euro 2,991 compared with euro 3,675 for ID, translating into a 19% annual cost difference of euro 684/patient. Base case results were robust to varying assumptions for insulin dose, insulin price, change in weight and proportion of ID once daily administrations.. IG and ID basal-bolus regimes have comparative safety and efficacy, based on the Hollander study, IG however may represent a significantly more cost saving option for T2D patients in Germany requiring basal-bolus insulin analogue therapy with potential annual cost savings of euro 684/patient compared to ID.

Topics: Blood Glucose Self-Monitoring; Cost Savings; Costs and Cost Analysis; Diabetes Mellitus, Type 2; Drug Costs; Germany; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Insurance, Health; Models, Econometric; Needles; Randomized Controlled Trials as Topic; Reagent Strips

Topics: Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Labeling; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Research Design; Treatment Outcome

We compared blood glucose profile when glargine or detemir was injected once daily before dinner in combination with pre-meal insulin lispro by a crossover design. Glargine showed lower post-dinner and bedtime glucose levels in Type 1 diabetes, and lower pre-dinner and post-dinner glucose levels in Type 2 diabetes than detemir.

Topics: Adult; Aged; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Male; Middle Aged; Postprandial Period

Insulin is normally added to oral glucose-lowering drugs in people with type 2 diabetes when glycaemic control becomes suboptimal. We evaluated outcomes in people starting insulin therapy with neutral protamine Hagedorn (NPH), detemir, glargine or premixed insulins.. Insulin-naïve people with type 2 diabetes (n = 8009), ≥ 35 years old, HbA(1c) ≥ 6.5% and begun on NPH (n = 1463), detemir (n = 357), glargine (n = 2197) or premix (n = 3992), were identified from a UK database of primary care records (The Health Improvement Network). Unadjusted and multivariate-adjusted analyses were conducted, with persistence of insulin therapy assessed by survival analysis.. In the study population (n = 4337), baseline HbA(1c) was 9.5 ± 1.6%, falling to 8.4 ± 1.5% over 12 months (change -1.1 ± 1.8%, p < 0.001). Compared with NPH, people taking detemir, glargine and premix had an adjusted reduction in HbA(1c) from baseline, of 0.00% (p = 0.99), 0.19% (p < 0.001) and 0.03% (p = 0.51). Body weight increased by 2.8 kg overall (p < 0.001), and by 2.3, 1.7, 1.9, and 3.3 kg on NPH, detemir, glargine and premix (p < 0.001 for all groups); insulin dose at 12 months was 0.70 (overall), 0.64, 0.61, 0.56 and 0.76 U/kg/day. After 36 months, 57% of people on NPH, 67% on glargine and 83% on premix remained on their initially prescribed insulin.. In routine clinical practice, people with type 2 diabetes commenced on NPH experienced a modest disadvantage in glycaemic control after 12 months compared with other insulins. When comparing the insulins, glargine achieved best HbA(1c) reduction, while premix showed greatest weight gain and the highest dose requirement, but had the best persistence of therapy.

Topics: Administration, Oral; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Insulins; Male; Medication Adherence; Middle Aged; Treatment Outcome; Weight Gain; 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

We report on three type 2 diabetic patients whose daily basal insulin dose requirements were substantially reduced after switching from insulin detemir to insulin glargine. Meta-analysis of three randomised trials of basal insulin initiation confirmed this increased insulin detemir dose requirement in type 2 patients. Potential explanations are discussed.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Meta-Analysis as Topic; Middle Aged; Randomized Controlled Trials as Topic; Weight Gain

PREDICTIVE is a large, observational study of the empirical use of insulin detemir in patients with type 1 or type 2 diabetes (T1DM/T2DM). This post hoc analysis evaluates insulin-naïve patients with T2DM uncontrolled on oral antidiabetic drugs (OADs) who were initiated and remained on once-daily insulin detemir for 12 weeks.. This observational, multinational, multi-center, open-label prospective study evaluated the efficacy and safety of insulin detemir in 1653 insulin-naïve patients with T2DM (mean age 60.8 +/- 10.9 years, BMI 29.8 +/- 4.8 kg/m(2), and HbA(1C) 8.82 +/- 1.50%). Statistical comparisons were made between baseline and 12-week follow up data. Our study was subject to the usual limitations of observational studies.. Endpoints were: incidence of serious adverse drug reactions, including number of hypoglycemic events (total, major, and nocturnal), glycemic parameters, and weight change.. Following insulin initiation, no significant change occurred in the number of nocturnal hypoglycemic events or total hypoglycemic events (p = 0.4513), and no serious adverse drug reactions were observed during the 12 weeks of treatment. HbA(1C) decreased by a mean 1.25% (SD +/- 1.25%; p < 0.0001), with 30% of patients (n = 383) achieving HbA(1C) <7% at 12 weeks. Mean changes in fasting blood glucose and fasting blood glucose variability were -3.62 mmol/L (SD +/- 2.93; p < 0.0001) and -0.48 mmol/L (SD +/- 1.03; p < 0.0001), respectively. Body weight decreased by a mean 0.5 kg (SD +/- 3.3; p < 0.0001), with weight loss or no weight change occurring in a substantial percentage of patients in each BMI category (<25, 25-30, 30-35, and >35 kg/m(2)). Patients with higher baseline BMI lost the most weight, with the greatest weight loss (-1.20 kg) reported in those with BMI >35 kg/m(2).. Empirical use of insulin detemir as an insulin initiation strategy can improve glycemic control with good tolerability, including a low risk of hypoglycemia and a weight benefit, in a majority of insulin-naïve patients uncontrolled on OADs.

Topics: Aged; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Administration Schedule; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Middle Aged; Safety

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

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 goal of this study was to compare daily insulin use, glycemic control, and health care costs in insulin-naive patients with type 2 diabetes who initiated treatment with either insulin detemir or insulin glargine.. This was a retrospective cohort analysis of health care claims data and laboratory results for adult, insulin-naive patients with type 2 diabetes who were enrolled in a large US managed care organization and initiated basal therapy with insulin detemir or insulin glargine between May 1, 2006, and December 31, 2006. The daily average consumption (DACON) of insulin was calculated as the total number of units dispensed (excluding the last fill) divided by the number of days between the index date and the date of the last fill of the index insulin. Glycemic control was evaluated by comparing mean glycosylated hemoglobin (HbA(1c)) values in the preindex period (the 180 days before the index date) and the follow-up period (the 180 days after the index date). Mean all-cause and diabetes-related health care costs in the preindex and follow-up periods were calculated and compared.. The analysis included 48 patients initiating therapy with insulin detemir and 258 initiating therapy with insulin glargine. The mean age of the 2 cohorts was approximately 54 years, and most patients in each cohort were male (52.1% and 59.7%, respectively). Few patients in either cohort had a baseline HbA(1c) value <7% (13% and 10%), suggesting poor glycemic control at the time of insulin initiation. After adjustment for confounders (eg, preindex diabetes medication), the DACON of insulin was comparable between cohorts (29.3 and 29.6 U/d; P = NS), as were follow-up HbA(1c) values (8.2% and 7.9%). Insulin detemir and insulin glargine also were associated with comparable mean adjusted all-cause pharmacy costs ($3074 and $2899), medical costs ($2319 and $3704), and total health care costs ($6014 and $7023). However, insulin glargine was associated with significantly higher mean adjusted diabetes-related medical costs compared with insulin detemir ($1510 vs $707, respectively; P = 0.03), as well as significantly higher mean adjusted total diabetes-related health care costs ($3408 vs $2261; P = 0.03).. In this managed care population of insulin-naive patients who initiated therapy with insulin detemir or insulin glargine, the daily insulin dose and glycemic control did not differ significantly between the 2 insulins. However, patients receiving insulin detemir incurred lower diabetes-related medical and total health care costs.

Topics: Biomarkers; Cost Savings; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Drug Costs; Drug Prescriptions; Female; Glycated Hemoglobin; Health Care Costs; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Managed Care Programs; Middle Aged; Models, Economic; Retrospective Studies; Treatment Outcome; United States

The insulin regimen of a Type 2 diabetic presenting for surgery had been changed recently from a 70/30 mixture of insulin aspart protamine and aspart to insulin detemir and insulin glulisine. Preoperative instructions were to take the usual dose of basal, but none of the short-acting insulin. On the morning of surgery, the patient's blood glucose was low and remained so despite i.v. dextrose administration. A review of the basal insulin dose revealed that it had been inappropriately increased to control elevated postprandial glucose. Doses of basal insulin in excess of basal requirements will cause hypoglycemia in the fasting state.

Topics: Adult; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Fasting; Female; Gynecologic Surgical Procedures; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Preoperative Care

Topics: Analysis of Variance; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Treatment Outcome; Weight Gain

Between 5 and 10% of the European population suffers from diabetes, and its prevalence is constantly rising, in Austria like in other countries. The main goals in the treatment of diabetes mellitus are the prevention of complications and organ damage, the prevention of severe hypo- and hyperglycaemia and the preservation of quality of life. Many patients with type 2 diabetes become insulin-dependent in the course of their disease. The application of a long acting insulin or insulin analogue is the simplest way of initiating an insulin therapy and is in accordance with current guidelines. Current scientific evidence shows that the use of long acting insulin analogues for type 2 diabetes; which can no longer be sufficiently controlled with oral antidiabetic agents, is simple, safe and efficacious. Thus, this treatment option should be available without any restrictions to physicians and patients in order to facilitate the beginning of an insulin regime. This position paper summarises up the current evidence concerning this subject.

Topics: Austria; Body Weight; Cohort Studies; Diabetes Mellitus, Type 2; Follow-Up Studies; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Myocardial Infarction; Practice Guidelines as Topic; Quality of Life; Randomized Controlled Trials as Topic; Retrospective Studies; Rosiglitazone; Thiazolidinediones

Topics: Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Reproducibility of Results

The aim of the present study was to investigate whether predetermined contact frequency with the study team and endpoint insulin dose are associated with study outcomes in basal insulin initiation trials in type 2 diabetes.. A systematic Medline search was performed. Using data from the selected studies, contact frequency was plotted against HbA(1c) reduction and endpoint insulin dose. The importance of face-to-face vs telephone contact was also analysed. Insulin dose was plotted against HbA(1c) reduction, hypoglycaemia rate and weight gain. To investigate non-specific study effects, the relationship between contact frequency and HbA(1c) was also assessed in dipeptidyl peptidase-4 (DPP-4) inhibitor trials.. The reduction in HbA(1c) was highly correlated with contact frequency and endpoint insulin dose (r (2) = 0.751, p < 0.001 and r (2) = 0.433, p = 0.008, respectively). However, after adjusting for contact frequency, the relationship between insulin dose and HbA(1c) reduction was no longer significant (p = 0.270). The frequency of both clinical and telephone contacts were independent predictors of HbA(1c) improvement (p = 0.010 and p < 0.001, respectively). We found no dose-response relationship between end-of-study insulin dose and hypoglycaemia or weight gain. In DPP-4 inhibitor studies, contact frequency was not positively associated with HbA(1c).. The frequency of contact with the study team is highly correlated with the improvement in HbA(1c) achieved in basal insulin initiation trials in type 2 diabetic patients. This has important implications for trial design and interpretation, as well as for clinical care.

Topics: Communication; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Professional-Patient Relations; Randomized Controlled Trials as Topic; Treatment Outcome

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

PREDICTIVE (an ongoing multinational observational study) provides an opportunity to explore the impact of insulin detemir use in routine clinical practice. Here, we report on long-term (52-week) data from a French cohort of patients (n=1772), comprising 643 with type 1 diabetes and 1129 with type 2 diabetes.. Patients were prescribed insulin detemir at their physician's discretion and assessed at various visits (baseline, 12 weeks, 26 weeks and 52 weeks). The primary endpoint was the frequency of serious adverse drug reactions, including major hypoglycaemia. Secondary endpoints included minor and nocturnal hypoglycaemia, glycaemic control (HbA(1c), fasting blood glucose and variability of fasting blood glucose) and weight change.. The incidence of serious adverse drug reactions was low throughout the study, seen in 10 patients with type 1 diabetes (14 events, 1.6%) and seven with type 2 diabetes (seven events, 0.6%). In both type 1 and type 2 diabetes cohorts, the overall minor and nocturnal hypoglycaemic events were reduced from baseline (P<0.001), with no clinically significant changes in weight from baseline to endpoint. After 52 weeks of treatment with insulin detemir, glycaemic control improved, with reductions in: HbA(1c), by -0.6% and -0.8% in type 1 and type 2 diabetes patients, respectively; fasting blood glucose, by -1.4mmol/L and -1.9mmol/L respectively; and FBG variability, by -0.8mmol/L and -0.3mmol/L, respectively (P<0.0001 for all).. Patients treated with insulin detemir in a clinical healthcare setting improved their glycaemic control with no increases in hypoglycaemia, adverse events or weight compared with baseline.

Topics: Adult; Aged; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; France; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Longitudinal Studies; Male; Middle Aged; Treatment Outcome

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

Glargine and detemir are long-acting human insulin analogues with a smooth peakless profile of action. Although their binding affinities to the insulin receptor have been studied, little is known about the subsequent signalling properties activated after the binding. We directly compared intracellular signalling properties of them in various cultured cells. Regarding the metabolic signalling, glargine and insulin-induced comparable dose-dependent phosphorylation of insulin receptor, IRS-1, Akt, and GSK3, whereas detemir-induced kinetics were markedly lower in 3T3-L1 adipocytes and L6 myocytes. A similar pattern of phosphorylation induction was observed in primary hepatocytes and vascular smooth muscle cells (VSMCs). Because of the binding of detemir to albumin with high affinity, the phosphorylation kinetics and glucose uptake of detemir, but not glargine, decreased with increasing concentrations of BSA. Concerning the mitogenic properties, glargine and insulin-induced comparable dose-dependent phosphorylation of MAP kinase (MAPK) and 5-bromo-2'-deoxyuridine (BrdU) incorporation. Detemir-induced phosphorylation of MAPK was apparently reduced, whereas it stimulated BrdU incorporation with relatively similar dose-dependent manner in VSMCs. These results indicate that glargine has comparable properties to human insulin in metabolic and mitogenic signalling and action. In contrast, detemir-induced metabolic signaling is less potent in all cell types studied, and is reduced further by increasing concentrations of albumin.

Topics: 3T3 Cells; Animals; Cell Culture Techniques; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glucose; Humans; Insulin; Insulin Detemir; Insulin Glargine; Insulin Secretion; Insulin-Secreting Cells; Insulin, Long-Acting; Mice; Muscle Cells; Signal Transduction

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

Topics: Administration, Oral; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Combinations; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting

Topics: Diabetes Mellitus, Type 2; Drug Eruptions; Humans; Hypoglycemic Agents; Injections; Insulin; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged; Time Factors

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged

Topics: Child, Preschool; Cost-Benefit Analysis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Financing, Personal; Germany; Humans; Insulin; Insulin Detemir; Insulin, Long-Acting; Insurance, Pharmaceutical Services; National Health Programs

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

The aim of this study was to evaluate the safety and efficacy of insulin detemir in type 2 diabetes patients previously receiving NPH insulin (NPH group, n = 175) or insulin glargine (glargine group, n = 118) in combination with oral antidiabetic drugs (OADs).. Patients were transferred to insulin detemir, while the OAD regimen and number of injections remained the same. The incidence of serious adverse drug reactions, including major hypoglycaemia, and haemoglobin A(1c) (HbA(1c)), fasting glucose, within-patient fasting glucose variability and body weight change were measured at 14 weeks.. Glycaemic control improved in both NPH (HbA(1c) = -0.2%, p < 0.05; fasting glucose -1.0 mmol/l, p < 0.0001) and glargine (HbA(1c) = -0.6%, p < 0.0001; fasting glucose -1.4 mmol/l, p < 0.0001) groups, including a reduction in fasting glucose variability (p < 0.01 for both). The incidence of total and nocturnal hypoglycaemia was reduced in both NPH and glargine groups. The incidence of major hypoglycaemia was low and did not change significantly during the follow-up period. Mean body weight was significantly reduced in the NPH (-0.7 kg, p < 0.01) and glargine (-0.5 kg, p < 0.05) groups.. These results indicate that in type 2 diabetes, transferring from other basal insulins to insulin detemir in combination with OADs was associated with improvements in glycaemic control, which were accompanied by a reduced risk of hypoglycaemia and a reduction in body weight.

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

Predictable Results and Experience in Diabetes through Intensification and Control to Target: an International Variability Evaluation (PREDICTIVE) is a multi-national, open-label, prospective, observational study assessing the safety and efficacy of insulin detemir in clinical practice. This post hoc subanalysis evaluates insulin-naïve patients on oral antidiabetic drugs (OADs) who were initiated on insulin detemir as basal therapy (+/- OADs).. The European cohort of the PREDICTIVE study currently includes 20,531 patients (12,981 with type 2 diabetes) who were prescribed insulin detemir and followed up for 12, 26 or 52 weeks. Here, we report data from a subgroup of 2377 OAD-treated, insulin-naïve type 2 diabetes patients for a mean follow-up of 14.4 weeks. Patients were prescribed insulin detemir as basal therapy (+/- OADs) by their physician, as part of routine clinical care. Results were reported in comparison with baseline observations.. One serious adverse drug reaction was reported, which was a major hypoglycaemic episode. Treatment with insulin detemir (+/- OADs) significantly reduced mean haemoglobin A(1c) (HbA(1c)) (-1.3%; p < 0.0001), fasting glucose (-3.7 mmol/l; p < 0.0001), and within-patient fasting glucose variability (-0.5 mmol/l; p < 0.0001). In the majority of patients (82%), these improvements in glycaemic control were achieved with once daily administration of insulin detemir. There was a small reduction in mean body weight (-0.7 kg; p < 0.0001), which was most apparent in patients with a higher body mass index (BMI) at baseline. A significant negative relationship between weight change and baseline BMI was observed (greater the BMI, greater the weight reduction). Multiple regression analysis showed that BMI and HbA(1c) at baseline, and change in HbA(1c), were all predictors for weight change (p < 0.0001 for all), with BMI being the strongest predictor.. Patients with type 2 diabetes naïve to insulin can be effectively treated with once-daily insulin detemir (+/- OADs) to achieve improved glycaemic control with no adverse effect on weight and a low risk of hypoglycaemia. These short-term results are consistent with the findings of clinical trials.

Topics: Cohort Studies; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged; Prospective Studies

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

PREDICTIVE (Predictable Results and Experience in Diabetes through Intensification and Control to Target: An International Variability Evaluation) is a large, multi-national, open-label, prospective, observational study assessing the safety and efficacy of insulin detemir in clinical practice. A total of 20,531 patients with type 1 or 2 diabetes from 11 countries were prescribed insulin detemir and followed up after a mean of 14.4 weeks. The primary endpoint was incidence of serious adverse drug reactions (SADRs), including major hypoglycaemia. Secondary endpoints were: haemoglobin A(1c) (HbA(1c)), mean self-monitored fasting glucose, within-patient fasting glucose variability and body weight change. Two hundred and fourteen patients (1%) reported SADRs, including major hypoglycaemia. The incidence of major hypoglycaemic episodes was reduced from 3.0/patient-year at baseline to 0.7/patient-year at follow-up in type 1 patients (p < 0.0001), and from 0.8 to 0.1/patient-year in type 2 patients (p < 0.0001). Insulin detemir improved glycaemic control in type 1 and type 2 patients, with reductions in mean HbA(1c) (0.5% and 0.9%, respectively, p < 0.0001 for both), fasting glucose (1.7 and 2.6 mmol/l, p < 0.0001 for both) and within-patient fasting glucose variability (0.7 and 0.5 mmol/l, p < 0.0001 for both). There was a small decrease in mean body weight in both type 1 and 2 patients (-0.1 kg, p < 0.01 and -0.4 kg, p < 0.0001 respectively). Insulin detemir was used once- or twice-daily in 49% and 50% of type 1 patients, and 77% and 23% of type 2 diabetes patients, respectively. The 14-week observations from PREDICTIVE support clinical trial data showing that insulin detemir improves glycaemic control, with a lowered risk of hypoglycaemia and no weight gain.

Topics: Adult; Aged; Blood Glucose; Body Weight; Cohort Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged; Prospective Studies; 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

PREDICTIVEtrade mark (Predictable Results and Experience in Diabetes through Intensification and Control to Target: An International Variability Evaluation) is a large, multi-national, observational study assessing the safety and efficacy of insulin detemir. We report the study design, population characteristics and baseline observations, including cross-sectional analysis, from 19 911 patients with type 1 or 2 diabetes.. Patients with type 1 or 2 diabetes requiring basal insulin are prescribed insulin detemir and followed up for 12-52 weeks. Data on demographics, haemoglobin A(1c) (HbA(1c)), fasting glucose, within-subject fasting glucose variability and weight are collected from patient records (and/or recall for hypoglycaemia). A negative binomial distribution model is used to assess the influence of predictive/confounding variables on hypoglycaemic episodes in insulin-treated patients at baseline. Multi-factorial analysis of covariance is used to evaluate the association of the variables with current body weight and within-subject fasting glucose variability.. Total hypoglycaemic episodes in the 4 weeks prior to study start were 47.5 per patient-year in patients with type 1 and 9.2 per patient-year in patients with type 2 diabetes. The frequency of hypoglycaemia in insulin-treated patients showed a significant, positive association with duration of diabetes, number of insulin injections and fasting glucose variability but was inversely related to HbA(1c), fasting glucose and body mass index. Weight showed a significant positive association with gender (male > female) and insulin dosage. Weight was also positively associated with fasting glucose variability in patients with type 1 diabetes, and age and number of injections in patients with type 2 diabetes.. These baseline data showed that, in addition to the established relationship with intensive treatment and HbA(1c), frequency of hypoglycaemia was positively associated with fasting glucose variability. Follow-up data from PREDICTIVE will provide insights on insulin detemir in diabetes management.

Topics: Adult; Blood Glucose; Body Mass Index; Body Weight; Cross-Sectional Studies; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged; Prospective Studies; Sex Factors; Treatment Outcome

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

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

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 highlight the pharmacology, clinical data, and practical application for the use of insulin detemir, a new long-acting insulin analog in the treatment of type 2 diabetes.. Published clinical, pharmacokinetic, and pharmacodynamic studies of insulin detemir, as well as contemporary studies and reviews about the management of patients with type 2 diabetes.. Insulin therapy, if titrated appropriately, is the most physiological and effective intervention for lowering blood glucose and may help preserve beta-cell function in patients with type 2 diabetes. Insulin detemir, in comparative clinical trials, has been shown to provide effective glycemic control and a consistent blood glucose-lowering response for up to 24 h, a decreased incidence of nocturnal hypoglycemia, and less weight gain than other basal insulin formulations.. Insulin therapy is often met with resistance from both patients and healthcare providers because of concerns about its effectiveness, hypoglycemia, injections, and weight gain. Insulin detemir, designed to closely mimic basal insulin secretion, may help overcome some of the barriers to effective diabetes management, i.e., hypoglycemia and weight gain, and lead to better outcomes.

Topics: Attitude of Health Personnel; Attitude to Health; Blood Glucose Self-Monitoring; Chemistry, Pharmaceutical; Diabetes Mellitus, Type 2; Disease Progression; Drug Administration Schedule; Fear; Glycated Hemoglobin; Humans; Hypoglycemia; Incidence; Injections, Subcutaneous; Insulin; Insulin Detemir; Insulin, Long-Acting; Patient Selection; Treatment Outcome; Weight Gain

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

The second basal insulin analog for type 1 and type 2 diabetes. How does it compare to NPH? And to glargine (Lantus).

Topics: Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting

Insulin detemir (Levemir) is a soluble long-acting human insulin analog acylated with a 14-carbon fatty acid. The fatty acid modification allows insulin detemir to reversibly bind to albumin, thereby providing slow absorption and a prolonged and consistent metabolic effect of up to 24 hours in patients with type 1 or type 2 diabetes mellitus. Insulin detemir has a more predictable, protracted, and consistent effect on blood glucose than neutral protamine Hagedorn (NPH) insulin, with less intrapatient variability in glycemic control than NPH insulin or insulin glargine. Insulin detemir, administered once or twice daily, is at least as effective as NPH insulin in maintaining overall glycemic control, with a similar or lower risk of hypoglycemia, especially nocturnal hypoglycemia, compared with NPH insulin in patients with type 1 or type 2 diabetes. Insulin detemir also provides the added clinical benefit of no appreciable bodyweight gain in patients with type 1 diabetes and less bodyweight gain than NPH insulin in patients with type 2 diabetes. Insulin detemir is, therefore, a promising new option for basal insulin therapy in patients with type 1 or 2 diabetes.

Topics: Adolescent; Adult; Child; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Randomized Controlled Trials as Topic

Topics: Blood Glucose; Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Injections, Subcutaneous; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Time Factors

In the treatment of diabetes, the positive correlation between weight gain and glycaemic control is well known. Inappropriate weight gain has been demonstrated in landmark diabetes studies, with insulin or oral antidiabetic drugs. Weight increase is associated with accelerated deterioration in beta-cell function in type II diabetes, and increases in hypertension and lipid levels in both type I and type II diabetes. Concerns about increasing weight may be a barrier to initiation or to intensification of insulin therapy. Insulin introduction may be delayed in type II diabetes, and patients may under-dose their insulin to avoid gaining weight. Insulin detemir is a new long-acting soluble insulin analogue where protraction is achieved by reversible binding to albumin. As a result, it has consistent absorption and low variability from injection to injection. Studies of insulin detemir in basal-bolus regimens in type I and type II diabetes have shown significantly less weight gain compared with NPH. There is speculation about potential mechanisms for these outcomes and results from ongoing investigations are awaited. The insulin detemir data suggest that weight gain with insulin therapy is not inevitable. The potential therefore exists for improving glycaemic control while maintaining weight stability, resulting in immediate and long-term benefits for patients.

Topics: Blood Glucose; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Infusion Systems; Insulin, Long-Acting; Weight Gain

Topics: Biological Availability; Clinical Trials as Topic; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Approval; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting