insulin-detemir and Hypoglycemia

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

People with type 1 diabetes mellitus (T1DM) need treatment with insulin for survival. Whether any particular type of (ultra-)long-acting insulin provides benefit especially regarding risk of diabetes complications and hypoglycaemia is unknown.. To compare the effects of long-term treatment with (ultra-)long-acting insulin analogues to NPH insulin (neutral protamine Hagedorn) or another (ultra-)long-acting insulin analogue in people with type 1 diabetes mellitus.. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Scopus, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform and the reference lists of systematic reviews, articles and health technology assessment reports. We explored the US Food and Drug Administration (FDA) and European Medical Agency (EMA) web pages. We asked pharmaceutical companies, EMA and investigators for additional data and clinical study reports (CSRs). The date of the last search of all databases was 24 August 2020.. We included randomised controlled trials (RCTs) with a duration of 24 weeks or more comparing one (ultra-)long-acting insulin to NPH insulin or another (ultra-)long-acting insulin in people with T1DM.. Two review authors assessed risk of bias using the new Cochrane 'Risk of bias' 2 (RoB 2) tool and extracted data. Our main outcomes were all-cause mortality, health-related quality of life (QoL), severe hypoglycaemia, non-fatal myocardial infarction/stroke (NFMI/NFS), severe nocturnal hypoglycaemia, serious adverse events (SAEs) and glycosylated haemoglobin A1c (HbA1c). We used a random-effects model to perform meta-analyses and calculated risk ratios (RRs) and odds ratios (ORs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs) and 95% prediction intervals for effect estimates. We evaluated the certainty of the evidence applying the GRADE instrument.. We included 26 RCTs. Two studies were unpublished. We obtained CSRs, clinical study synopses or both as well as medical reviews from regulatory agencies on 23 studies which contributed to better analysis of risk of bias and improved data extraction. A total of 8784 participants were randomised: 2428 participants were allocated to NPH insulin, 2889 participants to insulin detemir, 2095 participants to insulin glargine and 1372 participants to insulin degludec. Eight studies contributing 21% of all participants comprised children. The duration of the intervention varied from 24 weeks to 104 weeks. Insulin degludec versus NPH insulin: we identified no studies comparing insulin degludec with NPH insulin. Insulin detemir versus NPH insulin (9 RCTs): five deaths reported in two studies including adults occurred in the insulin detemir group (Peto OR 4.97, 95% CI 0.79 to 31.38; 9 studies, 3334 participants; moderate-certainty evidence). Three studies with 870 participants reported QoL showing no true beneficial or harmful effect for either intervention (low-certainty evidence). There was a reduction in severe hypoglycaemia in favour of insulin detemir: 171/2019 participants (8.5%) in the insulin detemir group compared with 138/1200 participants (11.5%) in the NPH insulin group experienced severe hypoglycaemia (RR 0.69, 95% CI 0.52 to 0.92; 8 studies, 3219 participants; moderate-certainty evidence). The 95% prediction interval ranged between 0.34 and 1.39. Only 1/331 participants in the insulin detemir group compared with 0/164 participants in the NPH insulin group experienced a NFMI (1 study, 495 participants; low-certainty evidence). No study reported NFS. A total of 165/2094 participants (7.9%) in the insulin detemir group compared with 102/1238 participants (8.2%) in the NPH insulin group experienced SAEs (RR 0.95, 95% CI 0.75 to 1.21; 9 studies, 3332 participants; moderate-certainty evidence). Severe nocturnal hypoglycaemia was observed in 70/1823 participants (3.8%) in the insulin detemir group compared with 60/1102 participants (5.4%) in the NPH insulin group (RR 0.67, 95% CI 0.39 to 1.17; 7 studies, 2925 participants; moderate-certainty evidence). The MD in HbA1c comparing insulin detemir with NPH insulin was 0.01%, 95% CI -0.1 to 0.1; 8 studies, 3122 participants; moderate-certainty evidence. Insulin glargine versus NPH insulin (9 RCTs): one adult died in the NPH insulin group (Peto OR 0.14, 95% CI 0.00 to 6.98; 8 studies, 2175 participants; moderate-cert. Comparing insulin detemir with NPH insulin for T1DM showed lower risk of severe hypoglycaemia in favour of insulin detemir (moderate-certainty evidence). However, the 95% prediction interval indicated inconsistency in this finding. Both insulin detemir and insulin glargine compared with NPH insulin did not show benefits or harms for severe nocturnal hypoglycaemia. For all other main outcomes with overall low risk of bias and comparing insulin analogues with each other, there was no true beneficial or harmful effect for any intervention. Data on patient-important outcomes such as QoL, macrovascular and microvascular diabetic complications were sparse or missing. No clinically relevant differences were found between children and adults.

Topics: Adolescent; Adult; Bias; Child; Child, Preschool; Confidence Intervals; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Myocardial Infarction; Quality of Life; Randomized Controlled Trials as Topic; Stroke; Young Adult

To revisit the data analysis used to inform National Institute of Health and Care Excellence (NICE) NG17 guidance for initiating basal insulin in adults with type 1 diabetes mellitus (diabetes).. We replicated the data, methodology and analysis used by NICE diabetes in the NG17 network meta-analysis (NMA). We expanded this data cohort to a more contemporary data set (extended 2017 NMA) and restricted the studies included to improve the robustness of the data set (restricted 2017 NMA) and in a post hoc analysis, changed the index comparator from neutral protamine Hagedorn (NPH) insulin twice daily to insulin detemir twice daily.. The absolute changes in HbA. In NG17, comparisons of basal insulins were based solely on efficacy of glycaemic control. Many of the trials used in this analysis were treat-to-target, which minimize differences in HbA

Topics: Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Network Meta-Analysis; Practice Guidelines as Topic

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

The comparison between long acting insulin analogues (LAIA) and human insulin (NPH) has been investigated for decades, with many randomized controlled trials (RCTs) and systematic reviews giving mixed results. This overlapping and contradictory evidence has increased uncertainty on coverage decisions at health systems level.. To conduct an overview of systematic reviews and update existing reviews, preparing new meta-analysis to determine whether LAIA are effective for T1D patients compared to NPH.. We identified systematic reviews of RCTs that evaluated the efficacy of LAIA glargine or detemir, compared to NPH insulin for T1D, assessing glycated hemoglobin (A1C) and hypoglycemia. Data sources included Pubmed, Cochrane Library, EMBASE and hand-searching. The methodological quality of studies was independently assessed by two reviewers, using AMSTAR and Jadad scale. We found 11 eligible systematic reviews that contained a total of 25 relevant clinical trials. Two reviewers independently abstracted data.. We found evidence that LAIA are efficacious compared to NPH, with estimates showing a reduction in nocturnal hypoglycemia episodes (RR 0.66; 95% CI 0.57; 0.76) and A1C (95% CI 0.23; 0.12). No significance was found related to severe hypoglycemia (RR 0.94; 95% CI 0.71; 1.24).. This study design has allowed us to carry out the most comprehensive assessment of RCTs on this subject, filling a gap in diabetes research. Our paper addresses a question that is important not only for decision makers but also for clinicians.

Topics: Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Models, Statistical; Randomized Controlled Trials as Topic; Regression Analysis

In the past decade, there has been much advancement in oral antidiabetic agents, but few changes in insulin therapy. With the addition of the ultra-long-acting insulins, insulin glargine U300 (IGlar 300) and insulin degludec (IDeg 100 and IDeg 200), it is important to understand key aspects in the agents' clinical properties, efficacy, safety, dosing, packaging, and place in therapy.. A literature review was conducted using PubMed database and was limited to English, full-text articles published from January 2000 to January 2018. The following search terms were used: insulin glargine 300, insulin degludec, Toujeo, Tresiba, and ultra-long-acting insulin.. These agents are longer acting with sustained insulin coverage as compared with other basal insulins while having a low potential for hypoglycemia. Efficacy and safety profiles are quite good, and potential for weight gain was similar to IGlar 100.. Depending on the patient's needs, these newer agents may offer some advantages. Insulin glargine U300 and IDeg 200 are concentrated, allowing for administration of large doses by less volume, thereby theoretically improving absorption. For patients needing flexible dosing, IDeg may be beneficial. The ultra-long-acting agents may also be useful if it is suspected that the basal insulin is not lasting the entire day.

Topics: Blood Glucose; Diabetes Mellitus; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Patient Safety; Prevalence; Weight Gain

Manufacturers of insulin products for diabetes therapy have long sought ways to modify the absorption rate of exogenously administered insulins in an effort to better reproduce the naturally occurring pharmacokinetics of endogenous insulin secretion. Several mechanisms of protraction have been used in pursuit of a basal insulin, for which a low injection frequency would provide tolerable and reproducible glucose control; these mechanisms have met with varying degrees of success. Before the advent of recombinant DNA technology, development focused on modifications to the formulation that increased insulin self-association, such as supplementation with zinc or the development of preformed precipitates using protamine. Indeed, NPH insulin remains widely used today despite a frequent need for a twice-daily dosing and a relatively high incidence of hypoglycaemia. The early insulin analogues used post-injection precipitation (insulin glargine U100) or dimerization and albumin binding (insulin detemir) as methods of increasing therapeutic duration. These products approached a 24-hour glucose-lowering effect with decreased variability in insulin action. Newer basal insulin analogues have used up-concentration in addition to precipitation (insulin glargine U300), and multihexamer formation in addition to albumin binding (insulin degludec), to further increase duration of action and/or decrease the day-to-day variability of the glucose-lowering profile. Clinically, the major advantage of these recent analogues has been a reduction in hypoglycaemia with similar glycated haemoglobin control when compared with earlier products. Future therapies may bring clinical benefits through hepato-preferential insulin receptor binding or very long durations of action, perhaps enabling once-weekly administration and the potential for further clinical benefits.

Topics: Chemistry, Pharmaceutical; Diabetes Mellitus; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Lente; Insulin, Long-Acting; Recombinant Proteins

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

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

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

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

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

As basal insulin analogues are being used off-label, there is a need to evaluate their safety (maternal hypoglycaemia and fetal and perinatal outcomes) and efficacy [haemoglobin A1c(HbA1c), fasting plasma glucose, and maternal weight gain]. The aim of this review is to provide an overview of the current literature concerning basal insulin analogue use in diabetic pregnancy, and to present the design and preliminary, non-validated baseline characteristics of a currently ongoing randomized, controlled, open-label, multicentre, multinational trial comparing insulin detemir with neutral protamine hagedorn insulin, both with insulin aspart, in women with type 1 diabetes planning a pregnancy (n = 306) or are already pregnant (n = 164). Inclusion criteria include type 1 diabetes > 12 months' duration; screening HbA1c ≤ 9.0% (women recruited prepregnancy), or pregnant with gestational age 8-12 weeks and HbA1c ≤ 8.0% at randomization. At confirmation of pregnancy all subjects must have HbA1c ≤ 8.0%. Exclusion criteria include impaired hepatic function, cardiac problems, and uncontrolled hypertension. Subjects are randomized to either insulin detemir or neutral protamine hagedorn insulin, both with prandial insulin aspart. The results are expected mid-2011 with full publications expected later this year. Baseline characteristics show that basal insulin analogues are already frequently used in pregnant women with type 1 diabetes. This study will hopefully elucidate the safety and efficacy of the basal insulin analogue detemir in diabetic pregnancy.

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Off-Label Use; Pregnancy; Pregnancy in Diabetics

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

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

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

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

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

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

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 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

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

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

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

The treatment of diabetes was revolutionised shortly after the turn of the twentieth century by the extraction and purification of insulin. Methods to protract (i.e. prolong) the action of insulin were developed in the 1930s; little changed in the technology of insulin protraction until the turn of this century when, with renewed interest in the importance of basal insulin in controlling diabetes and thus preventing or delaying complications, technology advanced again. Two new long-acting insulin analogues have come to the market; some may be familiar with insulin glargine, which has been widely used for some years now. This review attempts to describe the novel method of protraction that insulin detemir (launched last summer) employs by albumin binding, to discuss the possible therapeutic benefits of this method of protraction and to describe the findings of studies comparing insulin detemir with other currently available long-acting insulin preparations. The intention of this article is not to review all of the currently available long-acting insulin analogues.

Topics: Delayed-Action Preparations; Diabetes Mellitus; Glucose; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting

A meta-analysis of results from four clinical trials in type 1 diabetes patients showed that insulin detemir (IDet)-based basal/bolus treatment of type 1 diabetes led to improved HbA1c (0.15%-points lower), reduced risk of major hypoglycaemic events (by 2%) and reduction in body mass index (BMI) (0.26 kg/m2) compared to protamine Hagedorn human (NPH) insulin-based basal/bolus therapy in type 1 patients.. A published, validated, peer-reviewed Markov simulation model (the CORE Diabetes Model) projected short-term results obtained from the fixed-effects (weighted average) meta-analysis to long-term incidence of complications, improvements in quality-adjusted life years (QALY), long-term costs and the cost-effectiveness for IDet combinations versus NPH combinations in type 1 diabetes patients. Probabilities of complications and HbA1c-dependent adjustments were derived from the DCCT and other studies. Costs of treating complications in the UK were retrieved from published sources. Total direct costs (complications + treatment costs) for each arm were projected over patient lifetimes from a UK National Heath Service perspective. Both costs and clinical outcomes were discounted at 3.5% annually.. Improved glycaemic control, decreased hypoglycaemic events and BMI with IDet-based basal/bolus therapy led to fewer diabetes-related complications, an increase in quality-adjusted life expectancy of 0.09 years, increased total lifetime costs/patient of 1707 pounds sterling and an incremental cost-effectiveness ratio of 19,285 pounds sterling per QALY gained. Results were stable under a wide range of reasonable assumptions.. Short-term improvements seen with IDet combinations versus NPH combinations led to decreased complications, improvements in QALYs and reductions in complication costs, which partially offset the additional costs of detemir, leading to a cost-effectiveness ratio which fell within a range considered to represent excellent value for money (< 35,000 pounds sterling/QALY gained).

Topics: Adolescent; Adult; Aged; Body Mass Index; Clinical Trials as Topic; Cost-Benefit Analysis; Diabetes Complications; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Models, Theoretical; United Kingdom

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

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

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

To compare the safety and efficacy of fast-acting insulin aspart (faster aspart) with conventional insulin aspart (IAsp) in adults with type 1 diabetes (T1D).. onset 1 was a randomized, multicentre, treat-to-target, phase III, 52-week (initial 26 weeks + additional 26 weeks) trial conducted at 165 sites across 9 countries. Adults with T1D were randomly allocated to double-blind mealtime faster aspart or IAsp, each with once- or twice-daily insulin detemir. The primary endpoint, change in glycated haemoglobin (HbA1c) from baseline after the initial 26 weeks, has been reported previously. In the present paper, we report data from the full 52-week study period.. Between August 2013 and June 2015, 381 participants were assigned to double-blind faster aspart and 380 participants to IAsp. After 52 weeks, estimated mean changes from baseline in HbA1c levels were -0.08% (faster aspart) and +0.01% (IAsp); estimated treatment difference significantly favoured faster aspart (-0.10% [95% confidence interval {CI} -0.19;-0.00]; P = .0424). Changes from baseline in 1-hour postprandial plasma glucose (PPG) increment (meal test; faster aspart -1.05 mmol/L; IAsp -0.14 mmol/L) also significantly favoured faster aspart (estimated treatment difference -0.91 mmol/L [95% CI -1.40;-0.43]; -16.48 mg/dL [95% CI -25.17;-7.80]; P = .0002). There was no difference in overall severe or blood glucose-confirmed hypoglycaemic episodes or treatment-emergent adverse events between treatments.. At 52 weeks, overall glycaemic control had significantly improved with faster aspart vs IAsp, consistent with the 26-week study findings. Achieving an insulin profile closer to physiological insulin secretion with faster aspart translates into lower PPG and HbA1c levels compared with those achieved with IAsp in people with T1D.

Topics: Adult; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Compounding; Drug Monitoring; Drug Therapy, Combination; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin Detemir; Male; Meals; Middle Aged

To evaluate the long-term safety and efficacy of a simplified basal-bolus regimen of once-daily insulin degludec/insulin aspart (IDegAsp) with additional IAsp vs. a standard basal-bolus insulin regimen of insulin detemir (IDet) with IAsp in adults with Type 1 diabetes.. This was an open-label trial comprising a 26-week core phase followed by a 26-week extension phase. Participants were randomized to IDegAsp once daily at the main meal and IAsp at remaining meals (IDegAsp+IAsp), or IDet (once or twice daily) and IAsp at all meals (IDet+IAsp). Insulins were titrated to target plasma glucose of < 5 mmol/l (< 90 mg/dl) at pre-breakfast (IDegAsp and IDet) and at pre-meal (IAsp).. Once-daily treatment with IDegAsp and IAsp as bolus insulin for remaining meals was associated with significantly lower risk of nocturnal confirmed hypoglycaemia, improved glycaemic control and showed non-inferiority compared with IDet+IAsp, the standard of care in Type 1 diabetes.

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Drug Combinations; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin Detemir; Insulin, Long-Acting; Meals; Treatment Outcome

To develop an algorithm that delivers an individualized dose of rapid-acting insulin after morning resistance exercise to counter post-exercise hyperglycaemia in individuals with Type 1 diabetes.. Eight people with Type 1 diabetes, aged 34 ± 7 years with HbA1c concentrations 72 ± 12 mmol/mol (8.7 ± 1.1%), attended our laboratory on two separate mornings after fasting, having taken their usual basal insulin the previous evening. These people performed a resistance exercise session comprising six exercises for two sets of 10 repetitions at 60% of the maximum amount of force that was generated in one maximal contraction (60% 1RM). In a randomized and counterbalanced order, the participants were administered an individualized dose of rapid-acting insulin (2 ± 1 units, range 0-4 units) immediately after resistance exercise (insulin session) by means of an algorithm or were not administered this (no-insulin session). Venous blood glucose concentrations were measured for 125 min after resistance exercise. Data (mean ± sem values) were analysed using anova (P ≤ 0.05).. Participants had immediate post-resistance exercise hyperglycaemia (insulin session 13.0 ± 1.6 vs. no-insulin session 12.7 ± 1.5 mmol/l; P = 0.834). The decline in blood glucose concentration between peak and 125 min after exercise was greater in the insulin exercise session than in the no-insulin session (3.3 ± 1.0 vs. 1.3 ± 0.4 mmol/l: P = 0.015). There were no episodes of hypoglycaemia (blood glucose <3.9 mmol/l).. Administration of rapid-acting insulin according to an individualized algorithm reduced the hyperglycaemia associated with morning resistance exercise without causing hypoglycaemia in the 2 h post-exercise period in people with Type 1 diabetes.

Topics: Adult; Blood Glucose; Combined Modality Therapy; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Dosage Calculations; Drug Monitoring; Drug Therapy, Combination; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin Detemir; Insulin Glargine; Pilot Projects; Precision Medicine; Resistance Training; Risk; United Kingdom

The long-term safety and tolerability of insulin degludec (IDeg) was compared with that of insulin detemir (IDet), as basal treatment in participants with type 1 diabetes mellitus (T1DM). In the present multinational, 26-week core + 26-week extension, controlled, open-label, parallel-group trial, adults with T1DM were randomized to IDeg or IDet as basal insulin treatment combined with meal-time bolus insulin aspart. IDeg was administered once daily, whilst IDet was administered once or twice daily depending on patients' glycaemic control. After 1 year, IDeg provided a 33% lower rate of nocturnal hypoglycaemia compared with IDet: estimated rate ratio (IDeg : IDet) 0.67 [95% confidence interval (CI) 0.51; 0.88]; p < 0.05. IDeg improved glycated haemoglobin after 1 year of treatment, similarly to IDet, but IDeg also provided a significantly greater reduction in fasting plasma glucose compared with IDet: estimated difference (IDeg - IDet) -1.11 (95% CI -1.83; -0.40) mmol/l; p < 0.05. The present study confirmed the long-term safety and tolerability profile of IDeg in patients with T1DM. IDeg provided a lower risk of nocturnal confirmed hypoglycaemia than IDet.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Drug Administration Schedule; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin Detemir; Insulin, Long-Acting; Male; Meals; Middle Aged; Time

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

To compare efficacy and safety of new insulin glargine 300 U/ml (Gla-300) with that of insulin glargine 100 U/ml (Gla-100) in Japanese adults with type 1 diabetes.. The EDITION JP 1 study (NCT01689129) was a 6-month, multicentre, open-label, phase III study. Participants (n = 243) were randomized to Gla-300 or Gla-100 while continuing mealtime insulin. Basal insulin was titrated with the aim of achieving a fasting self-monitored plasma glucose target of 4.4-7.2 mmol/l. The primary endpoint was change in glycated haemoglobin (HbA1c) over 6 months. Safety measures included hypoglycaemia and change in body weight.. Gla-300 was non-inferior to Gla-100 for the primary endpoint of HbA1c change over the 6-month period {least squares [LS] mean difference 0.13 % [95 % confidence interval (CI) -0.03 to 0.29]}. The annualized rate of confirmed (≤3.9 mmol/l) or severe hypoglycaemic events was 34 % lower with Gla-300 than with Gla-100 at night [rate ratio 0.66 (95 % CI 0.48-0.92)] and 20 % lower at any time of day [24 h; rate ratio 0.80 (95 % CI 0.65-0.98)]; this difference was most pronounced during the first 8 weeks of treatment. Severe hypoglycaemia was infrequent. The basal insulin dose increased in both groups (month 6 dose: Gla-300 0.35 U/kg/day, Gla-100 0.29 U/kg/day). A between-treatment difference in body weight change over 6 months favouring Gla-300 was observed [LS mean difference -0.6 kg (95 % CI -1.1 to -0.0); p = 0.035]. Adverse event rates were comparable between the groups.. In Japanese adults with type 1 diabetes using basal plus mealtime insulin, less hypoglycaemia was observed with Gla-300 than with Gla-100, particularly during the night, while glycaemic control did not differ.

Topics: Adult; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Drug Administration Schedule; 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

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

Insulin analogues reduce the risk of hypoglycaemia compared with human insulin in patients with type 1 diabetes (T1D) and minor hypoglycaemia problems. The HypoAna trial showed that, in patients with recurrent severe hypoglycaemia, treatment based on insulin analogues reduces the risk of severe hypoglycaemia. The present study aims to assess whether this also applies to non-severe hypoglycaemia events during the day and at night.. This 2-year investigator-initiated multicentre, prospective, randomized, open, blinded endpoint (PROBE) trial involved patients with T1D and at least two episodes of severe hypoglycaemia during the previous year. Using a balanced crossover design, patients were randomized to basal-bolus therapy based on analogue (detemir/aspart) or human (NPH/regular) insulins. A total of 114 participants were included. Endpoints were the number of severe hypoglycaemic events and non-severe events, including documented symptomatic and asymptomatic episodes occurring during the day and at night (ClinicalTrials.gov number: NCT00346996).. Analogue-based treatment resulted in a 6% (2-10%; P=0.0025) overall relative risk reduction of non-severe hypoglycaemia. This was due to a 39% (32-46%; P<0.0001) reduction of non-severe nocturnal hypoglycaemia, seen for both symptomatic (48% [36-57%]; P<0.0001) and asymptomatic (28% [14-39%]; P=0.0004) nocturnal hypoglycaemia episodes. No clinically significant differences in hypoglycaemia occurrence were observed between the insulin regimens during the day. The time needed to treat one patient with insulin analogues to avoid one episode (TNT1) of non-severe nocturnal hypoglycaemia was approximately 3 months.. In T1D patients prone to severe hypoglycaemia, treatment with analogue insulin reduced the risk of non-severe nocturnal hypoglycaemia compared with human insulin.

Topics: Adult; Aged; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Disease Susceptibility; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Male; Middle Aged; Severity of Illness Index

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

To compare the effectiveness of a free-mix of aspart (A) and detemir (D) insulins (ADIM) with a commonly used premixed fixed-ratio aspart and neutral protamine Hagedorn (NPH) insulin mixture (ANIM) in young children with type 1 diabetes (T1D) treated with twice-daily injections. The trial thus compares not only D vs. NPH, but also flexible, personalized insulin preparations vs. a fixed premixed preparation.. This single-center, open-label, randomized trial included 82 children with T1D. Patients stayed on ANIM for 1 yr of optimization of disease management, then were randomized to either ANIM (N = 41) or ADIM (N = 41) for another year.. Frequency of severe or symptomatic episodes, glycated hemoglobin A1c (HbA1c), and blood glucose (BG) values.. Compared with ANIM, ADIM decreases symptomatic hypoglycemia by approximately 2 fold (p < 0.001) and severe hypoglycemia by 7-10 fold (p = 0.04). ADIM somewhat reduced BG variation. Mean HbA1c was comparable on ADIM (7.9 ± 0.8 %; 63 ± 9 mmol/mol) and ANIM (8.2 ± 0.7 %; 66 ± 8 mmol/mol).. Using a free-mixing preparation of aspart and detemir insulin decreases hypoglycemia in young children with type 1 diabetes.

Topics: Adolescent; Blood Glucose; Child; Child, Preschool; Diabetes Mellitus, Type 1; Drug Combinations; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Male

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

Insulin degludec (IDeg) once-daily was compared with insulin detemir (IDet) once- or twice-daily, with prandial insulin aspart in a treat-to-target, randomized controlled trial in children 1-17 yr with type 1 diabetes, for 26 wk (n = 350), followed by a 26-wk extension (n = 280). Participants were randomized to receive either IDeg once daily at the same time each day or IDet given once or twice daily according to local labeling. Aspart was titrated according to a sliding scale or in accordance with an insulin:carbohydrate ratio and a plasma glucose correction factor. Randomization was age-stratified: 85 subjects 1-5 yr. (IDeg: 43), 138 6-11 yr (IDeg: 70) and 127 12-17 yr (IDeg: 61) were included. Baseline characteristics were generally similar between groups overall and within each stratification. Non-inferiority of IDeg vs. IDet was confirmed for HbA1c at 26 wk; estimated treatment difference (ETD) 0.15% [-0.03; 0.32]95% CI . At 52 wk, HbA1c was 7.9% (IDeg) vs. 7.8% (IDet), NS; change in mean FPG was -1.29 mmol/L (IDeg) vs. +1.10 mmol/L (IDet) (ETD -1.62 mmol/L [-2.84; -0.41]95% CI , p = 0.0090) and mean basal insulin dose was 0.38 U/kg (IDeg) vs. 0.55 U/kg (IDet). The majority of IDet treated patients (64%) required twice-daily administration to achieve glycemic targets. Hypoglycemia rates did not differ significantly between IDeg and IDet, but confirmed and severe hypoglycemia rates were numerically higher with IDeg (57.7 vs. 54.1 patient-years of exposure (PYE) [NS] and 0.51 vs. 0.33, PYE [NS], respectively) although nocturnal hypoglycemia rates were numerically lower (6.0 vs. 7.6 PYE, NS). Rates of hyperglycemia with ketosis were significantly lower for IDeg vs. IDet [0.7 vs. 1.1 PYE, treatment ratio 0.41 (0.22; 0.78)95% CI , p = 0.0066]. Both treatments were well tolerated with comparable rates of adverse events. IDeg achieved equivalent long-term glycemic control, as measured by HbA1c with a significant FPG reduction at a 30% lower basal insulin dose when compared with IDet. Rates of hypoglycemia did not differ significantly between the two treatment groups; however, hyperglycemia with ketosis was significantly reduced in those treated with IDeg.

Topics: Adolescent; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Infant; Insulin Aspart; Insulin Detemir; Insulin, Long-Acting

To compare, using a continuous glucose monitoring (CGM) system, the effect on glycaemic variability of insulin glargine, detemir and lispro protamine.. A total of 49 white people with type 1 diabetes, not well controlled by three times daily insulin lispro, taken for at least 2 months before study and on a stable dose, were enrolled. The study participants were randomized to add insulin glargine, detemir or lispro protamine, once daily, in the evening. We used a CGM system, the iPro Digital Recorder (Medtronic MiniMed, Northridge, CA, USA) for 1 week. Glycaemic control was assessed according to mean blood glucose values, the area under the glucose curve above 3.9 mmol/l (AUC(>3.9)) or above 10.0 mmol/l (AUC(>10.0)), and the percentage of time spent with glucose values >3.9 or >10.0 mmol/l. Intraday glycaemic variability was assessed using standard deviation (s.d.) values, the mean amplitude of glycaemic excursions and continuous overlapping of net glycaemic action. Day-to-day glycaemic variability was assessed using the mean of daily differences.. The s.d. was found to be significantly lower with insulin lispro protamine and glargine compared with insulin detemir. AUC(>3.9) was higher and AUC(>10.0) was lower with insulin lispro protamine and glargine compared with detemir. The mean amplitude of glycaemic excursions and continuous overlapping net glycaemic action values were lower with insulin lispro protamine and glargine compared with detemir. In addition, the mean of daily differences was significantly lower with insulin lispro protamine and glargine compared with detemir. Fewer hypoglycaemic events were recorded during the night-time with insulin lispro protamine compared with glargine and detemir.. The results suggest that insulin lispro protamine and glargine are more effective than detemir in reducing glycaemic variability and improving glycaemic control in people with type 1 diabetes. Insulin lispro protamine seems to lead to fewer hypoglycaemic events than other insulin regimens.

Topics: Adult; Analysis of Variance; Area Under Curve; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Double-Blind Method; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin Lispro; Male; Young Adult

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 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

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

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

Insulin analogues have been developed to reduce the risk of hypoglycaemia in patients with diabetes who require insulin-based treatment, but their effect on this endpoint in patients with type 1 diabetes complicated by recurrent severe hypoglycaemia is unknown. We compared the occurrence of severe hypoglycaemic episodes in such patients during treatment with insulin analogues or human insulin.. In this investigator-initiated, prospective, randomised, open-label, blinded-endpoint crossover trial at seven medical centres in Denmark, we recruited patients (aged ≥18 years) with type 1 diabetes (diagnosed for >5 years) who had reported two or more episodes of severe hypoglycaemia in the preceding year. Patients were randomly assigned (1:1) using computer-generated site-specific randomisation lists in blocks of four to treatment with basal-bolus therapy with either analogue insulin (detemir and aspart) or human insulin (human neutral protamine Hagedorn and human regular) in a balanced crossover design. A 1-year plus 1-year treatment period was specified, consisting of two 3-month run-in periods, each followed by a 9-month maintenance period. The primary endpoint was the number of validated episodes of severe hypoglycaemia (defined by need for treatment assistance from others) reported during the maintenance periods, analysed by intention to treat. The study is registered with ClinicalTrials.gov, number NCT00346996.. Between May 9, 2007, and Oct 30, 2009, 159 patients were randomly assigned. 18 patients discontinued during the first run-in period, leaving 141 patients in the intention-to-treat population. 136 severe hypoglycaemic episodes were reported during treatment with human insulin and 105 episodes were reported during treatment with insulin analogues, resulting in an absolute rate reduction of 0.51 episodes (95% CI 0.19-0.84) per patient-year with insulin analogues. This result corresponds to a relative rate reduction of 29% (95% CI 11-48; p=0.010).. Treatment with insulin detemir and aspart in patients with type 1 diabetes and recurrent severe hypoglycaemia resulted in a clinically significant reduced rate of severe hypoglycaemia compared with human insulin. Patients with the greatest chance of benefitting from improved insulin therapy should be offered treatment with insulin analogues and be included in future trials of new insulins.. Novo Nordisk A/S.

Topics: Cross-Over Studies; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged; Prospective Studies; Risk Factors; Secondary Prevention

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

To assess the efficacy and safety of insulin detemir administered once vs. twice daily in children and adolescents with type 1 diabetes mellitus.. In this prospective, open-label, treat-to-target study, 37 patients [mean age 12.7 ± 3 yr; diabetes duration 4.2 ± 3 yr, hemoglobin A1c (HbA1c) 8.8 ± 0.8%] were scheduled to receive insulin detemir once daily before breakfast, with pre-meal insulin aspart, for 16-20 wk. Detemir dose titration algorithm was based on age-related target fasting blood glucose levels during 4-8 wk. Patients achieving target range continued on once-daily detemir (Group A) if up-titration could not be done due to hypoglycemia patients were switched to twice-daily detemir (Group B).. Nineteen (51%) patients continued with once-daily detemir. HbA1c decreased significantly in both groups (A: -0.7%, p = 0.02; B: -0.8%, p = 0.004), without a significant difference between groups. The frequency of nocturnal hypoglycemic events/week decreased in both groups but a significant change was found only in Group A (10.9-2.7, p < 0.05 vs. 8.7-5.8, NS), with no change in frequency of severe hypoglycemic episodes in either group. No significant differences were found between and within groups for body mass index-standard deviation score, insulin requirement or treatment satisfaction. Group B patients were significantly younger than Group A patients (11.5 ± 2.3 vs.13.8 ± 3.2 yr, p = 0.01), with a higher percentage in active puberty (50 vs. 11%, p = 0.003).. Since twice-daily determir showed no clinical advantage over once-daily detemir, it appears reasonable to commence all children on once-daily detemir, taking into consideration that younger children and those in active puberty may require twice-daily therapy (ClinicalTrials.gov number, NCT00542399).

Topics: Adolescent; Algorithms; Child; Cohort Studies; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Monitoring; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Aspart; Insulin Detemir; Insulin, Long-Acting; Israel; Male

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

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

This randomised (1:1), multinational, open-labelled, parallel group trial compared insulin detemir (IDet) with neutral protamine Hagedorn (NPH) insulin, in combination with mealtime insulin aspart, over 1 yr in subjects aged 2-16 yr with type 1 diabetes mellitus. Of 348 randomised subjects, 82 (23.6%) were 2-5 yr (IDet: 42, NPH: 40). This article is a descriptive subgroup analysis of these young children. Baseline characteristics (IDet vs. NPH) were similar: mean age, 4.3 vs. 4.5 yr; diabetes duration, 2.2 vs. 2.1 yr; males, 42.9 vs. 52.5%. Mean haemoglobin A1c (HbA1c) was similar between groups at baseline (8.2 vs. 8.1%), and changed little over 1 yr (8.1 vs. 8.3%). Fasting plasma glucose (FPG) was similar at baseline (8.44 vs. 8.56 mmol/L) and decreased during the study (-1.0 vs. -0.45 mmol/L). A lower rate of hypoglycaemia was observed with IDet compared with NPH (24-h; 50.6 vs. 78.3 episodes per patient-year; nocturnal hypoglycaemia, 8.0 vs. 17.4 episodes per patient-year). No severe hypoglycaemic episodes occurred with IDet, while 3 subjects reported 6 episodes with NPH. Change in weight standard deviation score standardised by age and gender was -0.17 with IDet and +0.03 with NPH. A slightly lower proportion of subjects in this age group reported adverse events with IDet than with NPH (69.0 vs. 77.5%). Serious adverse events were few (5 with IDet, 7 with NPH). In conclusion, long-term treatment with IDet in children aged 2-5 yr suggested similar glycaemic control, greater reduction in FPG, lower rates of hypoglycaemia, no inappropriate weight gain, and fewer adverse events compared with NPH.

Topics: Body Weight; Child, Preschool; Diabetes Mellitus, Type 1; Europe; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male

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

As basal insulin analogues are being used off-label, there is a need to evaluate their safety (maternal hypoglycaemia and fetal and perinatal outcomes) and efficacy [haemoglobin A1c(HbA1c), fasting plasma glucose, and maternal weight gain]. The aim of this review is to provide an overview of the current literature concerning basal insulin analogue use in diabetic pregnancy, and to present the design and preliminary, non-validated baseline characteristics of a currently ongoing randomized, controlled, open-label, multicentre, multinational trial comparing insulin detemir with neutral protamine hagedorn insulin, both with insulin aspart, in women with type 1 diabetes planning a pregnancy (n = 306) or are already pregnant (n = 164). Inclusion criteria include type 1 diabetes > 12 months' duration; screening HbA1c ≤ 9.0% (women recruited prepregnancy), or pregnant with gestational age 8-12 weeks and HbA1c ≤ 8.0% at randomization. At confirmation of pregnancy all subjects must have HbA1c ≤ 8.0%. Exclusion criteria include impaired hepatic function, cardiac problems, and uncontrolled hypertension. Subjects are randomized to either insulin detemir or neutral protamine hagedorn insulin, both with prandial insulin aspart. The results are expected mid-2011 with full publications expected later this year. Baseline characteristics show that basal insulin analogues are already frequently used in pregnant women with type 1 diabetes. This study will hopefully elucidate the safety and efficacy of the basal insulin analogue detemir in diabetic pregnancy.

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Off-Label Use; Pregnancy; Pregnancy in Diabetics

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

To compare different administration times of insulin detemir (IDet) in patients with type 1 diabetes and poor metabolic control.. This 24-week open study included 39 people with type 1 diabetes mellitus (DM) randomized to one injection of IDet before lunch (mean 14.24 + or - 00.36 (+ or - SD) h) or at bedtime (23.19 + or - 0.42 h). Whenever target glycemia levels were not reached, the regimen was switched to insulin therapy with two injections (IDet-12h). Insulin aspart was used before main meals.. At week 24, only 12.2% of patients remained in the IDet bedtime group and 30.3% in the IDet before lunch group. The remaining 57.5% joined the IDet-12h group. There were no differences between the IDet before lunch and IDet bedtime groups. A subanalysis including the three groups demonstrated better metabolic control in the IDet before lunch group (glycosylated hemoglobin (HbA1c) 7.1 + or - 0.2 vs. 7.6 + or - 0.4 and 8.1 + or - 0.2% in IDet before-lunch, IDet bedtime and IDet-12h, respectively; p<0.05). An HbA1c value below 7% was achieved in 30.3% of the patients: 15.2% in the IDet before-lunch group, 3.3% in the IDet bedtime group and 12.2% in IDet-12h group. Quality of life did not differ among treatment groups.. One injection of IDet administered before lunch could improve metabolic control. However, most patients required two injections of IDet.

Topics: Adolescent; Adult; Biomarkers; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Monitoring; Eating; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Injections, Subcutaneous; Insulin; Insulin Aspart; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged; Postprandial Period; Quality of Life; Sleep; Young Adult

The efficacy of two basal insulins, insulin lispro protamine suspension (ILPS) and insulin detemir, was compared in basal-bolus regimens in Type 1 diabetes.. In this 32-week, multinational, parallel-group, randomized, controlled trial, adult patients with Type 1 diabetes received ILPS or insulin detemir, injected twice daily (before breakfast and bedtime) and prandial insulin lispro three times daily. The primary outcome was change in glycated haemoglobin (HbA(1c)) from baseline to endpoint.. Least squares mean (+/-se) changes in HbA(1c) were similar between groups, meeting non-inferiority (margin, 0.4%): -0.69 +/- 0.07% for ILPS and -0.59 +/- 0.07% for insulin detemir [between-treatment difference -0.10%; 95% confidence interval (CI) -0.29, 0.10]. Standard deviation of fasting blood glucose was similar (non-inferiority margin 0.8 mmol/l): 2.74 +/- 0.14 mmol/l for ILPS and 2.38 +/- 0.14 mmol/l for insulin detemir (CI -0.03, 0.75). Patients on ILPS gained more weight (1.59 +/- 0.23 kg vs. 0.62 +/- 0.24 kg; CI 0.34, 1.60; margin 1.5 kg). Weight-adjusted daily total and prandial insulin doses were lower for ILPS (prandial insulin, 0.38 +/- 0.01 U/kg/day for ILPS, 0.44 +/- 0.01 U/kg/day for insulin detemir; P = 0.004); daily basal insulin dose was similar. All hypoglycaemia incidence and rate and nocturnal hypoglycaemia incidence were similar between groups; nocturnal hypoglycaemia rate was lower for insulin detemir (mean +/- sd 0.79 +/- 1.23 for ILPS, 0.49 +/- 0.85 for insulin detemir; P = 0.001). Severe hypoglycaemia rate was 0.03 +/- 0.11 for ILPS and 0.02 +/- 0.10 for insulin detemir (P = 0.37).. ILPS-treated patients with Type 1 diabetes achieved similar glycaemic control as insulin detemir-treated patients after 32 weeks. Glucose variability was similar. While weight gain and nocturnal hypoglycaemia rate were statistically higher with ILPS, the clinical relevance is unclear.

Topics: Adult; Analysis of Variance; Blood Glucose; Body Weight; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Detemir; Insulin Lispro; Insulin, Long-Acting; Male; Middle Aged

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

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

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

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 long-acting insulin analogue detemir (Levemir) has structural and physicochemical properties which differ from human insulin. The aim of the present study was to test whether this leads to altered hormone and symptom response during hypoglycaemia.. 12 healthy subjects [6f/6m, age 32 +/- 6 years (mean +/- s.d.), body mass index (BMI) 24.2 +/- 2.5 kg/m(2)] underwent a 200-min stepwise hypoglycaemic clamp (45 min steps of 4.4, 3.7, 3.0 and 2.3 mmol/l) with either detemir or human insulin in random order. A bolus of detemir (660 mU/kg) or human insulin (60 mU/kg) was given before insulin was infused at a rate of 5 (detemir) or 2 (human insulin) mU/kg/min. Blood was drawn and a semi-quantitative symptom questionnaire was administered before and after each plateau of the hypoglycaemic clamp. Cognitive function was assessed during each step.. Blood glucose levels and glucose infusion rates were comparable with detemir and human insulin. The total symptom score was higher with detemir during the 3 and 2.3 mmol glucose step compared to human insulin (p = 0.048). Especially sweating was increased with detemir (p = 0.02) with an earlier and faster increase during the clamp (interaction insulin x time: p = 0.04). No significant differences between detemir and human insulin in cortisol, norepinephrine, epinephrine, glucagon, growth hormone, lactate or free fatty acid (FFA) levels during hypoglycaemia were observed, and there were no significant differences in cognitive function tests.. Insulin detemir increased symptom awareness during hypoglycaemia compared to human insulin in healthy individuals, whereas counter-regulatory hormone response and cognitive function were unaltered.

Topics: Adult; Blood Glucose; Cognition; Cross-Over Studies; Female; Glucose Clamp Technique; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Male; Surveys and Questionnaires; Treatment Outcome

We compared the symptoms of hypoglycaemia induced by insulin detemir (NN304) (B29Lys(epsilon-tetradecanoyl),desB30 human insulin) and equally effective doses of neutral protamine Hagedorn (NPH) insulin in relation to possible differential effects on hepatic glucose production and peripheral glucose uptake.. After overnight intravenous infusion of soluble human insulin 18 participants with type 1 diabetes received subcutaneous injections of NPH insulin or insulin detemir (0.5 U/kg body weight) on separate occasions in random order. During the ensuing gradual development of hypoglycaemia cognitive function and levels of counter-regulatory hormones were measured and rates of endogenous glucose production and peripheral glucose uptake continuously evaluated using a primed constant infusion of [6,6-(2)H(2)]glucose. The study was terminated when plasma glucose concentration had fallen to 2.4 mmol/l or had reached a minimum at a higher concentration.. During the development of hypoglycaemia no difference between the two insulin preparations was observed in symptoms or hormonal responses. Significant differences were seen in rates of glucose flux. At and below plasma glucose concentrations of 3.5 mmol/l suppression of endogenous glucose production was greater with insulin detemir than with NPH insulin, whereas stimulation of peripheral glucose uptake was greater with NPH insulin than with insulin detemir.. In participants with type 1 diabetes subcutaneously injected insulin detemir exhibits relative hepatoselectivity compared with NPH insulin, but symptoms of hypoglycaemia and hormonal counter-regulation are similar.. ClinicalTrials.gov NCT00760448.

Topics: Blood Glucose; Blood Pressure; Cross-Over Studies; Diabetes Mellitus, Type 1; Double-Blind Method; Epinephrine; Glucose; Growth Hormone; Heart Rate; Humans; Hypoglycemia; Hypoglycemic Agents; Infusions, Intravenous; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Liver; Patient Selection; Reaction Time

The primary study objective was to determine whether insulin detemir (detemir) was noninferior to insulin glargine (glargine) as the basal insulin in a basal-bolus regimen, with insulin aspart as the mealtime insulin, in terms of glycemic control at the end of 52 weeks in patients with type 1 diabetes mellitus (T1DM).. This multinational, open-label, parallel-group, treat-to-target, noninferiority trial enrolled patients aged > or = 18 years who had had T1DM for at least 12 months, had been taking a basal-bolus insulin regimen for at least 3 months, and had a glycosylated hemoglobin (HbA1c) value < or = 11.0% at screening. Patients were randomized in a 2:1 ratio to receive either detemir or glargine for 52 weeks. The basal insulin was initially administered once daily (in the evening) in both groups; if patients in the detemir group were achieving the plasma glucose (PG) target before breakfast but not before dinner, they were switched to twice-daily administration. Glargine was administered once daily throughout the trial, according to its approved labeling. Each patient attended 13 study visits and received 16 scheduled telephone calls from the trial site. The primary efficacy end point was glycemic control (HbA1c) after 52 weeks of treatment. Secondary end points included the number of patients achieving an HbA1c value < or = 7.0%, with or without a major hypoglycemic episode in the last month of treatment; fasting PG (FPG); within-patient variation in self-monitored plasma glucose (SMPG) before breakfast and dinner; and 10-point SMPG profiles. The noninferiority margin was 0.4%, consistent with US Food and Drug Administration guidelines.. Four hundred forty-three patients (mean [SD] age, 42 [12] years; body mass index, 26.5 [4.0] kg/m2; duration of diabetes, 17.2 [11.4] years; HbA1c, 8.1% [1.1%]) received study treatment. After 52 weeks, the estimated mean HbA1c did not differ significantly between the detemir and glargine groups (7.57% and 7.56%, respectively; mean difference, 0.01%; 95% CI, -0.13 to 0.16), consistent with the noninferiority of detemir to glargine. The corresponding estimated changes in HbA1c were -0.53% and -0.54%. In the 90 patients who completed the trial on once-daily detemir and the 173 patients who completed the trial on twice-daily detemir, the estimated changes in HbA1c were -0.49% and -0.58%, respectively. After 52 weeks, there were no significant differences in the proportions of those receiving detemir and glargine who achieved an HbA1c value < or = 7.0% without major hypoglycemia (31.9% and 28.9%, respectively). In addition, there were no significant differences in estimated mean FPG (8.58 and 8.81 mmol/L; mean difference, -0.23 mmol/L; 95% CI, -1.04 to 0.58) or in basal insulin doses. The basal insulin dose was numerically higher in patients receiving detemir twice rather than once daily (0.47 vs 0.33 U/kg, respectively). The relative risks for total and nocturnal hypoglycemia with detemir versus glargine were 0.94 and 1.12, respectively (both, P = NS). Six patients (2.0%) randomized to the detemir group and 4 (2.7%) randomized to the glargine group withdrew due to adverse events.. During 52 weeks of basal-bolus therapy in patients with T1DM, detemir was noninferior to glargine in terms of overall glycemic control (HbA1c). When used according to the approved labeling, detemir and glargine did not differ in tolerability or in terms of the occurrence of hypoglycemia.

Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 1; Double-Blind Method; Endpoint Determination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Sample Size; Treatment Outcome

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

The acylated long-acting insulin analog detemir is more lipophilic than human insulin and likely crosses the blood-to-brain barrier more easily than does human insulin. The aim of these studies was to assess the brain/hypothalamus responses to euglycemia and hypoglycemia in humans during intravenous infusion of equipotent doses of detemir and human insulin.. Ten normal, nondiabetic subjects (six men, age 36+/-7 years, and BMI 22.9+/-2.6 kg/m(2)) were studied on four occasions at random during intravenous infusion of either detemir or human insulin in euglycemia (plasma glucose 90 mg/dl) or during stepped hypoglycemia (plasma glucose 90, 78, 66, 54, and 42 mg/dl steps).. Plasma counterregulatory hormone response to hypoglycemia did not differ between detemir and human insulin. The glycemic thresholds for adrenergic symptoms were higher with detemir (51 +/- 7.7 mg/dl) versus human insulin (56 +/- 7.8 mg/dl) (P = 0.029). However, maximal responses were greater with detemir versus human insulin for adrenergic (3 +/- 2.5 vs. 2.4 +/- 1.8) and neuroglycopenic (4 +/- 3.9 vs. 2.7+/-2.5) symptoms (score, P < 0.05). Glycemic thresholds for onset of cognitive dysfunction were lower with detemir versus human insulin (51 +/- 8.1 vs. 47 +/- 3.6 mg/dl, P = 0.031), and cognitive function was more deteriorated with detemir versus human insulin (P < 0.05).. Compared with human insulin, responses to hypoglycemia with detemir resulted in higher glycemic thresholds for adrenergic symptoms and greater maximal responses for adrenergic and neuroglycopenic symptoms, with an earlier and greater impairment of cognitive function. Additional studies are needed to establish the effects of detemir on responses to hypoglycemia in subjects with diabetes.

Topics: 3-Hydroxybutyric Acid; Adult; Alanine; Blood Glucose; Brain; C-Peptide; Dose-Response Relationship, Drug; Fatty Acids, Nonesterified; Glucose; Glycerol; Humans; Hypoglycemia; Insulin; Insulin Detemir; Insulin, Long-Acting; Lactic Acid; Male; Middle Aged; Time Factors

PREDICTIVE is a multi-national, prospective, observational study, assessing the safety and efficacy of insulin detemir in patients with diabetes.. The European cohort includes 20,531 patients with diabetes (7420 type 1) from 11 countries. A subgroup of 4782 type 1 patients were transferred from a basal-bolus regimen with NPH insulin (n = 3117) or insulin glargine (n = 1665) to insulin detemir basal-bolus therapy; or from a human insulin basal-bolus regimen (n = 570) to insulin detemir/insulin aspart (part of the pre-study NPH group). Mean follow-up was 14.4 weeks. The primary endpoint was serious adverse drug reactions (SADRs), including major hypoglycaemia. Secondary endpoints were: incidence of overall and nocturnal hypoglycaemia; haemoglobin A(1c) (HbA(1c)); fasting glucose; within-patient fasting glucose variability; and change in body weight.. SADRs were reported by 62 (2.0%) patients previously receiving NPH insulin, 45 (2.7%) patients previously receiving insulin glargine and seven (1.2%) patients previously receiving human basal-bolus insulins. Major hypoglycaemia was significantly reduced in NPH insulin (55%), insulin glargine (51%), and human basal-bolus insulin groups (54%; p < 0.0001 for all). Total and nocturnal hypoglycaemic episodes were also significantly reduced in all groups (p < 0.0001 for all). HbA(1c) was reduced in patients previously receiving NPH insulin (0.5%), insulin glargine (0.4%), and human basal-bolus insulins (0.6%; p < 0.0001 for all). Mean fasting glucose and within-patient fasting glucose variability significantly decreased in all patients (p < 0.0001 for all). Body weight remained stable.. In this open-label, prospective, observational study, insulin detemir basal-bolus therapy improved glycaemic control and reduced hypoglycaemia with weight neutrality in type 1 patients in actual clinical practice.

Topics: Adult; Adverse Drug Reaction Reporting Systems; Body Weight; Diabetes Mellitus, Type 1; Drug-Related Side Effects and Adverse Reactions; Europe; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Prospective Studies; Treatment Outcome

This study compared the effect of insulin detemir on glycaemic control (HbA(1c), fasting plasma glucose and variability thereof) with that of Neutral Protamine Hagedorn human isophane (NPH) insulin, both combined with insulin aspart, in children with Type 1 diabetes mellitus, and compared the safety of these treatments.. In this 26-week, open-label, randomized (2 : 1), parallel-group study, 347 (140 prepubertal and 207 pubertal) children with Type 1 diabetes, aged 6-17 years, received insulin detemir (n = 232) or NPH insulin (n = 115) once or twice daily, according to the prestudy regimen, plus premeal insulin aspart.. The mean HbA(1c) decreased by approximately 0.8% with both treatments. After 26 weeks, the mean difference in HbA(1c) was 0.1% (95% confidence interval -0.1, 0.3) (insulin detemir 8.0%, NPH insulin 7.9%). Within-subject variation in self-measured fasting plasma glucose was significantly lower with insulin detemir than with NPH insulin (SD 3.3 vs. 4.3, P < 0.001), as was mean fasting plasma glucose (8.4 vs. 9.6 mmol/l, P = 0.022). The risk of nocturnal hypoglycaemia (22.00-07.00 h) was 26% lower with insulin detemir (P = 0.041) and the risk of 24-h hypoglycaemia was similar with the two treatments (P = 0.351). The mean body mass index (BMI) Z-score was lower with insulin detemir (P < 0.001).. Basal-bolus treatment with insulin detemir or NPH insulin and premeal insulin aspart in children and adolescents with Type 1 diabetes mellitus improved HbA(1c) to a similar degree. The lower and more predictable fasting plasma glucose, lower risk of nocturnal hypoglycaemia and lower BMI observed with insulin detemir are clinically significant advantages compared with NPH insulin.

Topics: Adolescent; Child; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Drug-Related Side Effects and Adverse Reactions; Female; Glucose Tolerance Test; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Risk Factors

To compare glycaemic control and risk of hypoglycaemia of twice-daily insulin detemir with once-daily insulin glargine in subjects with Type 1 diabetes.. In this 26-week, multicentre, open-label, parallel-group trial, 320 subjects with Type 1 diabetes received either insulin detemir twice daily or insulin glargine once daily. each in combination with premeal insulin aspart.. After 26 weeks, HbA(1c) had decreased from 8.8 to 8.2% in the insulin detemir group and from 8.7 to 8.2% in the insulin glargine group. Home-measured fasting plasma glucose (PG) was lower with insulin glargine than with insulin detemir (7.0 vs. 7.7 mmol/l, P < 0.001). The overall shape of the home-measured nine-point PG profiles was comparable between treatments (P = 0.125). Overall, there was no significant difference in within-subject variation in PG (P = 0.437). Within-subject variation in predinner PG was lower with insulin detemir than with insulin glargine (P < 0.05). The overall risk of hypoglycaemia was similar with no differences in confirmed hypoglycaemia. However, the risk of severe and nocturnal hypoglycaemia was 72% and 32%, respectively, lower with insulin detemir than with insulin glargine (P < 0.05). Body weight gain was not significantly different comparing insulin detemir and insulin glargine (0.52 kg vs. 0.96 kg, P = 0.193).. Treatment with twice-daily insulin detemir or once-daily insulin glargine, each in combination with insulin aspart, resulted in similar glycaemic control. The overall risk of hypoglycaemia was comparable, whereas the risks of both severe and nocturnal hypoglycaemia were significantly lower with insulin detemir.

Topics: Adolescent; Adult; Aged; Austria; Blood Glucose; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Female; Germany; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Risk Factors; South Africa; Treatment Outcome

Hypoglycaemia remains a major barrier preventing optimal glycaemic control in Type 1 diabetes due to the limitations of conventional insulin preparations. We investigated whether basal-bolus therapy with insulin detemir (detemir), a new soluble basal insulin analogue, was more effective in reducing the risk of hypoglycaemia compared with NPH insulin (NPH).. In this multinational, open-label, cross-over trial, 130 individuals with Type 1 diabetes received detemir and NPH twice daily in a randomized order in combination with premeal insulin aspart (IAsp) during two 16-week treatment periods. Risk of hypoglycaemia was based on self-measured plasma glucose (SMPG) and self-reported episodes during the last 10 weeks of each period.. Risk of nocturnal and overall hypoglycaemia was, respectively, 50% and 18% lower with detemir than with NPH (P < 0.001). A total of 19 severe hypoglycaemic episodes occurred during treatment with detemir compared with 33 with NPH (NS). HbA(1c) decreased by 0.3% point with both treatments and was comparable at 7.6% (+/- sem 0.06%, 95% confidence interval -0.106, 0.108) after 16 weeks with similar doses of basal insulin. Within-person variation in mean plasma glucose was lower with detemir than with NPH (sd 3.00 vs. 3.33, P < 0.001), as was prebreakfast SMPG (P < 0.0001).. Detemir was associated with a significantly lower risk of hypoglycaemia compared with NPH at similar HbA1c when used in combination with mealtime IAsp. The more consistent plasma glucose levels observed with detemir may allow people to aim for tighter glycaemic control without an increased risk of hypoglycaemia.

Topics: Adult; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Treatment Outcome

This trial investigated the efficacy and safety of two different administration-time regimens with insulin detemir (IDet) to that of a conventional basal insulin regimen with NPH insulin (NPH).. This multinational, 16-week, open, parallel group trial included 400 people with Type 1 diabetes mellitus (DM) randomized to IDet either morning and before dinner (IDetmorn+din) or morning and bedtime (IDetmorn+bed), or to NPH morning and bedtime (NPHmorn+bed), all in combination with mealtime insulin aspart (IAsp).. HbA1c was comparable between the three groups after 16 weeks (P = 0.64), with reductions of 0.39-0.49% points. Lower fasting plasma glucose (FPG) was observed with IDetmorn+din and IDetmorn+bed compared with NPHmorn+bed (9.8 and 9.1 vs. 11.1 mmol/l, P = 0.006), whereas the IDet groups did not differ (P = 0.15). Within-person variation in self-measured FPG was significantly lower for both IDet regimens (sd IDetmorn+din 2.5, IDetmorn+bed 2.6 mmol/l) than for NPHmorn+bed (sd 3.1 mmol/l, P < 0.001), but was comparable between the IDet groups (P = 0.48). Ten-point plasma glucose profiles were lower between dinner and breakfast in the IDetmorn+din group (P = 0.043), compared with the two other groups. Risk of overall and nocturnal hypoglycaemia was similar for the three groups. Lower mean bodyweight was observed with IDet compared with NPH after 16 weeks (difference: (IDetmorn+din)-1.3 kg, P < 0.001, (IDetmorn+bed)-0.6 kg, P = 0.050).. Both IDet regimens were well tolerated and provided lower and less variable glucose levels with no, or less, weight gain than NPH at comparable HbA1c. IDet can be administered either at dinner or bedtime, with similar glycaemic control according to the need of the individual person.

Topics: Adolescent; Adult; Blood Glucose; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Treatment Outcome; Weight Loss

The purpose of this trial was to compare the effects of QD basal insulin replacement using insulin detemir versus neutral protamine Hagedorn (NPH) insulin in basal-bolus therapy in combination with regular human insulin (HI) in patients with type 1 diabetes mellitus (DM).. This was a 6-month, prospective, randomized, open-label, controlled, parallel-group trial conducted at 92 sites in Europe and Australia. The trial population included men and women with type 1 DM for at least 1 year aged > or = 18 years with glycosylated hemoglobin (HbA(1c)) <== 12% already taking QD basal-bolus treatment with an intermediate- or long-acting insulin and a fast-acting human insulin or insulin analogue as bolus insulin. Patients were randomly assigned (2:1) to 6 months of treatment with insulin detemir or NPH at bedtime in combination with HI with main meals. Main outcome measures were blood glucose control as assessed by HbA(1c), fasting plasma glucose (FPG), 9-point self-monitored blood glucose (SMBG) profiles, 24-hour continuous blood glucose profiles, hypoglycemia, weight gain, and adverse events.. Of the 749 patients randomized to treatment, 747 were exposed to trial products and included in the intent-to-treat analysis set. Seven hundred patients completed the trial: 465 (94.7%) in the insulin detemir group and 235 (91.8%) in the NPH group. After 6 months, FPG was lower with insulin detemir than with NPH (-1.16 mmol/L difference; P = 0.001), whereas HbA(1c) did not differ significantly between treatments (-0.12% [95% CI, -0.25 to 0.02]; P = NS). Day-to-day variability in self-measured fasting blood glucose was lower with insulin detemir (SD, 2.82 vs 3.60 mmol/L; P < 0.001). The overall shape of the 9-point SMBG profiles differed significantly between treatments (P = 0.006), with lower glucose levels before breakfast with insulin detemir than with NPH (P < 0.001). There was a 26% reduction in the relative risk of nocturnal hypoglycemia with insulin detemir compared with NPH (P = 0.003). Gain in body weight was significantly lower after 6 months with insulin detemir than with NPH (-0.54 kg difference; P = 0.024). The frequency and type of adverse events were similar between treatment groups.. In this study, QD administration of insulin detemir at bedtime resulted in lower fasting blood glucose levels with less day-to-day variability and less fluctuation from ean blood glucose levels over 24 hours than NPH insulin, combined with an overall reduction in the risk of nocturnal hypoglycemia. These findings suggest that evening administration of insulin detemir may provide an opportunity to further improve fasting blood glucose targets.

Topics: Adult; Blood Glucose; Carrier Proteins; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Prospective Studies

The aim of the trial was to compare the efficacy and tolerability of two types of basal-bolus therapy, using either the soluble long-acting basal insulin analogue, insulin detemir, in combination with the rapid-acting analogue, insulin aspart, or NPH insulin in combination with mealtime regular human insulin.. In this 18-week, 1:1 randomised, open-labelled, parallel trial, 595 patients with Type 1 diabetes mellitus received insulin detemir or NPH insulin in the morning and at bedtime in combination with mealtime insulin aspart or regular human insulin respectively.. Glycaemic control with insulin detemir/insulin aspart was improved in comparison with NPH insulin/regular human insulin (HbA1c: 7.88% vs 8.11%; mean difference: -0.22% point [95% CI: -0.34 to -0.10]; p<0.001). Self-measured 8-point plasma glucose profiles differed between the groups (p<0.001), with lower postprandial plasma glucose levels in the insulin detemir/insulin aspart group. Within-person day-to-day variation in plasma glucose was lower with insulin detemir/insulin aspart than with NPH insulin/regular human insulin (SD: 2.88 vs 3.12 mmol/l; p<0.001). Risk of overall and nocturnal hypoglycaemia (23.00-06.00 hours) was, respectively, 21% (p=0.036) and 55% (p<0.001) lower in the insulin detemir/insulin aspart group than in the NPH insulin/regular human insulin group. Body weight (adjusted for baseline and change in HbA1c) was 1 kg lower with insulin detemir/insulin aspart than with NPH insulin/regular human insulin (p<0.001).. Basal-bolus therapy using insulin detemir/insulin aspart offers a better balance of control and tolerability than with NPH insulin/regular human insulin. The low variability and more physiological action profiles generated with these insulin analogues resulted in improved glycaemic control with lower risk of hypoglycaemia and no concomitant body weight increase.

Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 1; Endpoint Determination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male

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

This trial compared the long-term safety and efficacy of the basal insulin preparations, insulin detemir and NPH insulin, in basal-bolus therapy for patients with type 1 diabetes.. This multinational open, parallel-group trial randomized patients to receive insulin detemir or NPH insulin twice daily in addition to mealtime human soluble insulin. Doses were titrated towards predefined glycemic targets. After an initial 6-month treatment period, patients were invited to participate in a 6-month extension period. A total of 289 from 421 elected to continue in the trial, of which 252 completed.. Glycemic control as assessed by hemoglobin A1c (insulin detemir, 7.88%; NPH insulin, 7.78%; difference not significant) and fasting plasma glucose (insulin detemir, 10.1 mmol/L; NPH insulin, 9.84 mmol/L; difference not significant) was similar in both treatment groups at end point, with hemoglobin A1c little changed from baseline and fasting plasma glucose slightly decreased. There was some evidence for a risk reduction for hypoglycemia in association with insulin detemir, although this was not statistically significant (relative risk overall hypoglycemia, 0.71, P = 0.139; relative risk nocturnal hypoglycemia, 0.71, P = 0.067), and hypoglycemic events were fewer in each of the 12 months. There was a significant treatment difference with regard to weight outcome; NPH insulin was associated with weight gain (1.4 kg), but there was no mean weight gain (-0.3 kg) in the insulin detemir cohort (baseline-adjusted between-group difference at 12 months, 1.66 kg, P = 0.002). There were no obvious between-group differences in other safety parameters.. Glycemic control is maintained with insulin detemir during long-term treatment. At equivalent glycemic control to NPH insulin, insulin detemir is associated with a lack of weight gain and a trend towards a reduced risk of nocturnal hypoglycemia when used in basal-bolus therapy with mealtime soluble human insulin.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 1; Drug Administration Schedule; Eating; Fasting; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Middle Aged

Insulin detemir is a soluble basal insulin analog with a unique mechanism of protracted action designed to reduce the variability associated with conventional basal insulins. This trial compared the glycemic control, risk of hypoglycemia, and effect on body weight of insulin detemir and NPH insulin in patients with type 1 diabetes treated with rapid-acting insulin aspart at meals.. This study was a 6-month multinational open parallel-group comparison conducted at 46 centers in five countries and included 448 patients with type 1 diabetes randomized 2:1 to insulin detemir or NPH insulin, respectively.. After 6 months, comparable HbA(1c) levels were found between the two treatment groups. Fasting plasma glucose tended to be lower in patients treated with insulin detemir, but this difference was not statistically significant (-0.76 mmol/l, P = 0.097). Within-subject variation in self-measured fasting blood glucose was lower with insulin detemir than with NPH insulin (SD 3.37 vs. 3.78 mmol/l, P < 0.001). Risk of hypoglycemia was 22% lower with insulin detemir than with NPH insulin (P < 0.05) and 34% lower for nocturnal (2300-0600) hypoglycemia (P < 0.005). Nightly plasma glucose profiles were smoother and more stable with insulin detemir (P = 0.05). Body weight was significantly lower with insulin detemir at the end of the trial (P < 0.001).. Treatment with insulin detemir resulted in more predictable glycemic control, with smoother plasma glucose profiles than NPH insulin and a significant reduction in the risk of hypoglycemia. The reduction in body weight with insulin detemir is a potential additional advantage. Regimens optimized for insulin detemir may be able to improve glycemic control beyond that possible with NPH insulin.

Topics: Adult; Blood Glucose; Body Weight; Carrier Proteins; Diabetes Mellitus, Type 1; Eating; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Risk Factors

Insulin detemir (NN304) is a soluble basal insulin analog developed to cover basal insulin requirements. This trial aimed to compare the blood glucose-lowering effect of insulin detemir with that of NPH insulin (NPH) and to evaluate the two treatments with regard to intrasubject variation of fasting blood glucose, incidence of hypoglycemia, dose requirements, and safety.. This multicenter open randomized crossover trial in 59 type 1 diabetic subjects comprised a 2-week run-in period on a basal-bolus regimen with NPH insulin once daily, followed by two 6-week periods of optimized basal-bolus therapy with either once-daily insulin detemir or NPH insulin.. The area under the curve, in the time interval 23:00-8:00, derived from 24-h serum glucose profiles, was not statistically significantly different for the two treatment periods (insulin detemir:NPH ratio 89.2:83.5, P = 0.59). The intrasubject variation in fasting blood glucose during the last 4 days of treatment was lower for insulin detemir compared with NPH (P < 0.001). Mean dose requirements of insulin detemir were 2.35 times higher (95% CI 2.22-2.48) compared with NPH. During the last week of treatment, fewer subjects experienced hypoglycemic episodes on insulin detemir (60%) compared with NPH treatment (77%) (P = 0.049).. Insulin detemir was as effective as NPH in maintaining glycemic control when administered at a higher molar dose. The results indicate that insulin detemir may provide more predictable fasting blood glucose with lower intrasubject variation and reduced risk of hypoglycemia compared with NPH.

Topics: Adolescent; Adult; Blood Glucose; Carrier Proteins; Cross-Over Studies; Diabetes Mellitus, Type 1; Humans; Hypoglycemia; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Kinetics; Middle Aged; Solubility

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

Insulin detemir (IDt) is long-acting insulin whose protraction mechanism is based on a covalently attached fatty acid to an insulin molecule. Utilizing the high affinity of fatty acids towards human serum albumin (HA), the modified detemir molecule binds with good affinity to HA, which functions as a reservoir that leads to a slow and prolonged release of insulin. However, questions were raised over potential interactions between other drugs and IDt through competitive binding on the binding site(s) of HA. In a previous study, concomitant use of esomeprazole (Esom) and erythromycin resulted in severe hypoglycemia, and thus: the drugs including Esom were suggested as enhancers of IDt action through displacing it from its binding site on HA. To further study this possibility, studies utilizing different techniques including, semipermeable membrane dialysis, capillary electrophoresis, UV,NMR spectroscopy, and molecular docking were carried out. Results from various techniques supported the simultaneous binding of Esom along with IDt to HA (i.e., binding in two different sites without signs of competition between the two). Moreover, capillary electrophoresis suggested an increase in the binding affinity of Esom to HA in the presence of IDt (1.9 × 10

Topics: Drug Interactions; Esomeprazole; Fatty Acids; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Molecular Docking Simulation; Serum Albumin, Human

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

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

Historically, data on the rate of hyperglycemia and ketosis have not been collected in clinical trials. However, it is clinically important to assess the rate of these events in children with type 1 diabetes (T1D). This question was addressed in two pediatric trials using insulin degludec (degludec).. To assess the rate of hyperglycemia and ketosis in two-phase 3b trials investigating degludec (Study 1) and degludec with insulin aspart (IDegAsp [Study 2]) vs insulin detemir (IDet).. Patients (aged 1-17 years inclusive) with T1D treated with insulin for ≥3 months.. Study 1: patients were randomized to degludec once daily (OD) or IDet OD/twice daily (BID) for 26 weeks, followed by a 26-week extension phase. Study 2: patients were randomized to IDegAsp OD or IDet OD/BID for 16 weeks. Bolus mealtime IAsp was included in both studies. In Study 1, hyperglycemia was recorded if plasma glucose (PG) was >11.1 mmol/L, with ketone measurement required with significant hyperglycemia (>14.0 mmol/L). In Study 2, hyperglycemia was recorded with PG >14.0 mmol/L where the subject looked/felt ill, with ketone measurement also required in these hyperglycemic patients. In this post hoc analysis, the hyperglycemia threshold was 14.0 mmol/L for uniformity.. Despite similar rates of hyperglycemia with degludec/IDegAsp compared with IDet, the rates of ketosis were lower with degludec/IDegAsp.. These trials, the first to systematically collect data on ketosis in pediatric patients with T1D, demonstrate the potential of degludec/IDegAsp to reduce rates of metabolic decompensation, compared with IDet.

Topics: Adolescent; Blood Glucose; Child; Child, Preschool; Clinical Trials, Phase III as Topic; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Drug Combinations; Female; Humans; Hyperglycemia; Hypoglycemia; Infant; Insulin Aspart; Insulin Detemir; Insulin, Long-Acting; Male; Randomized Controlled Trials as Topic; Retrospective Studies

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

Hypoglycemia is an increasingly important endpoint in clinical diabetes trials. The assessment of hypoglycemia should therefore be as complete as possible. Blinded continuous glucose monitoring (CGM) provides an improved opportunity to capture asymptomatic and nocturnal events. Here we report results from the HypoAna trial comparing all-analog-insulin therapy (aspart/detemir) with all-human-insulin therapy (neutral protamine Hagedorn/regular) on non-severe hypoglycemia (symptomatic and asymptomatic hypoglycemia) as assessed by blinded CGM and compared with data obtained by self-monitoring of blood glucose (SMBG) in patients with type 1 diabetes and recurrent severe hypoglycemia.. Fifty-three patients completed a substudy of 4 × 3 days of blinded CGM. CGM traces were reviewed for hypoglycemic events lasting 15 min or longer.. At the threshold ≤3.9 mmol/L, the per-protocol analysis demonstrated a 40% rate reduction (95% confidence interval [CI] 20%-60%; P = 0.002) in nocturnal non-severe hypoglycemia during analog treatment, mainly due to a 40% rate reduction (95% CI 0%-70%; P = 0.03) of nocturnal asymptomatic hypoglycemia. Similar nonsignificant trends were seen at the glucose threshold ≤3.0 mmol/L. Overall CGM-detected that nocturnal asymptomatic hypoglycemia ≤3.9 mmol/L was ∼17 times more frequent than SMBG-detected episodes (52 vs. 3 events/patient-year). This translates into a time needed to treat one patient with insulin analogs to prevent one episode that is 34 times shorter using CGM data than SMBG data (1.4 vs. 47 weeks).. Capturing hypoglycemic events by the conventional method of SMBG in patients with impaired awareness reveals only a limited number of events. Blinded CGM can provide more complete data, particularly in terms of asymptomatic and nocturnal events.

Topics: Adult; Aged; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin Detemir; Male; Middle Aged

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

To determine if insulin detemir administration time affects the frequency of hypoglycemia (blood glucose level <70 mg/dl) in hospitalized patients.. Retrospective cohort study.. A total of 357 adults (aged 18-89 yrs) who received insulin detemir for at least 48 hours while hospitalized between January 1, 2014, and December 31, 2015, were included. Patients were categorized into one of three groups according to insulin detemir administration time: detemir given once/day between 7 a.m. and 10 a.m. (AM group [71 patients]), detemir given once/day between 6 p.m. and 10 p.m. (PM group [158 patients]), and detemir given twice/day (BID group [128 patients]).. Community hospital.. The primary outcome was the percentage of patient days with any occurrence of hypoglycemia. The key secondary outcomes included the percentages of patients who experienced any hypoglycemic event, severe hypoglycemia, hypoglycemia requiring treatment, and refractory hypoglycemia; time of hypoglycemia; and percentage of patients experiencing one or more episodes of hyperglycemia. The AM group had a lower proportion of days with hypoglycemia compared with the PM group (7.9% vs 11.9%, p=0.008). There was a nonsignificant trend toward a lower proportion of days with hypoglycemia in the BID group compared with the PM group (9.1% vs 11.9%, p=0.0302). No significant differences in percentage of patient days with hyperglycemia and rates of severe hypoglycemia, hypoglycemia requiring treatment, or refractory hypoglycemia were noted among the three groups.. Administration of detemir in the morning may reduce the occurrence of hypoglycemia in hospitalized patients. Institutions that include detemir on their formularies may consider evaluating the incidence of hypoglycemia and modifying administration schedules as part of their medication safety program.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Delayed-Action Preparations; Drug Administration Schedule; Female; Hospitalization; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Male; Middle Aged; Nevada; Retrospective Studies; Young Adult

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

The longer acting basal insulin analogs glargine and detemir have shown a lower incidence of hypoglycemia compared to insulin NPH in clinical studies. We evaluated the real-life risk of severe hypoglycemia among new users of insulins in the working-age population in Finland.. All persons aged 18-65 years with diabetes mellitus who were newly prescribed with insulins NPH, glargine, or detemir during 2006-2009, were identified from national registers. Risk of severe hypoglycemia requiring hospital care was compared between insulin types.. A total of 16,985 persons initiated basal insulin treatment (5586, 7499, and 3900 patients started NPH, glargine, and detemir, respectively) during follow-up. Five hundred and thirty-six persons were hospitalized because of severe hypoglycemia. Absolute rate (per 1000 patient-years) was 20.6 (95% CI 17.9, 23.8), 17.8 (15.6, 20.3), and 12.4 (9.9, 15.5) for NPH, glargine, and detemir initiators, respectively. With NPH as reference, the adjusted hazard ratio (HR) was 0.92 (95% CI 0.74, 1.15, p = 0.47) for glargine, and 0.70 (0.51, 0.94, p= 0.018) for detemir. The HR for detemir compared to glargine was 0.76 (0.58, 0.99, p = 0.040).. Initiating insulin treatment with detemir, but not with glargine, was associated with a significantly lower risk of severe hypoglycemia compared to NPH, among working-age adults. KEY MESSAGES The comparative safety of modern basal insulins regarding hypoglycemia among the working-age population is unclear. Large reductions in the incidence of severe hypoglycemia were seen among real-life patients who started insulin detemir, as compared to patients who initiated glargine or especially NPH insulin. Given the large amount of patients using insulin, these findings may have considerable clinical consequences at the population level.

Topics: Adult; Diabetes Mellitus; Female; Hospitalization; Humans; Hypoglycemia; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Longitudinal Studies; Male; Middle Aged; 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

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

Degludec is an ultralong-acting insulin analogue with a flat and reproducible pharmacodynamic profile. As some patients with type 1 diabetes (T1D) fail to achieve 24-h coverage with glargine or detemir despite twice-daily injections, we studied the effect of switching T1D patients from twice-daily glargine or detemir to degludec.. In this prospective observational study, T1D patients on twice-daily glargine or detemir were enrolled. At baseline and 12 weeks after switching to degludec, we recorded HbA1c, insulin dose, 30-day blood glucose self monitoring (SMBG) or 14-day continuous glucose monitoring (CGM), treatment satisfaction (DTSQ), fear of hypoglycemia (FHS). We included 29 patients (mean age 34 ± 11 years; diabetes duration 18 ± 10 years). After switching to degludec, HbA1c decreased from 7.9 ± 0.6% (63 ± 6 mmol/mol) to 7.7 ± 0.6% (61 ± 6 mmol/mol; p = 0.028). SMBG showed significant reductions in the percent and number of blood glucose values <70 mg/dl and in the low blood glucose index (LBGI) during nighttime. CGM showed a significant reduction of time spent in hypoglycemia, an increase in daytime spent in target 70-180 mg/dl, and a reduction in glucose variability. Total insulin dose declined by 17% (p < 0.001), with 24% reduction in basal and 10% reduction in prandial insulin. DTSQ and FHS significantly improved.. Switching from twice-daily glargine or detemir to once daily degludec improved HbA1c, glucose profile, hypoglycemia risk and treatment satisfaction, while insulin doses decreased. ClinicalTrials.govNCT02360254.

Topics: Adult; Biomarkers; Blood Glucose; Circadian Rhythm; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Substitution; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Italy; Male; Middle Aged; Patient Satisfaction; Prospective Studies; Risk Factors; Time Factors; Treatment Outcome; Young Adult

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

This study investigates the relationship between basal insulin regimen and glycaemic outcomes 12 months after skills-based structured education in the UK Dose Adjustment for Normal Eating (DAFNE) programme for Type 1 diabetes mellitus.. Retrospective analysis of data from 892 DAFNE participants from 11 UK centres.. Mean HbA1c 12 months after DAFNE was lower in those using twice- rather than once-daily basal insulin after correcting for differences in baseline HbA1c , age and duration of diabetes; difference -2 (95% CI -3 to -1) mmol/mol [-0.2 (-0.3 to -0.1)%], P = 0.009. The greatest fall in HbA1c of -5 (-7 to -3) mmol/mol [-0.4 (-0.6 to -0.3)%], P < 0.001 occurred in those with less good baseline control, HbA1c  ≥ 58 mmol/mol, who switched from once- to twice-daily basal insulin. There was no difference in the 12-month HbA1c between users of glargine, detemir and NPH insulin after correcting for other variables. Relative risk of severe hypoglycaemia fell by 76% and ketoacidosis by 63% 12 months after DAFNE. The rate of severe hypoglycaemia fell from 0.82 to 0.23 events/patient year in twice-daily basal insulin users. In the group with greatest fall in HbA1c , the estimated relative risk for severe hypoglycaemia in twice-daily basal insulin users versus once daily at 12 months was 1.72 (0.88-3.36, P = 0.110).. After structured education in adults with Type 1 diabetes mellitus, use of basal insulin twice rather than once daily was associated with lower HbA1c , independent of insulin type, with significant reductions in severe hypoglycaemia and ketoacidosis in all groups.

Topics: Adult; Blood Glucose; Cohort Studies; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Logistic Models; Male; Middle Aged; Patient Education as Topic; Retrospective Studies; Self Care; Treatment Outcome

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

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

Topics: Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin Detemir; Insulin, Long-Acting; Male

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

An ideal insulin regimen for children and adolescents with type 1 diabetes mellitus (T1DM) should be physiological, flexibile and predictable, protecting against hypoglycaemia. The aim of this study was to evaluate the influence of insulin analogues on glycaemic control and the occurance of hypoglycaemic episodes in children and adolescents with T1DM.. The study group consisted of 151 children and adolescents (90 boys, 61 girls) treated with human insulins for at least 12 months before introducing insulin analogues. All the patients were divided into two groups: the group I consisted of 72 (47.7%) patients treated with three injections of regular human insulin before meals and long-acting analogue (RHI/LA), and the group II of 79 (52.30%) patients treated with a combination of rapid-acting and long-acting analogue (RA/LA). The levels of glycated hemoglobin (HbA1c) and the number of hypoglycaemic episodes were assessed at the beginning of therapy with insulin analogues, and after 6 and 12 months.. The mean HbA1c was significantly lower in the group I (RHI/LA) after 6 months (9.15% vs 8.20%, p < 0.001) and after 12 months (9.15% vs 8.13%, p < 0.001) as well as in the group II (RA/LA) after 6 months (9.40% vs 8.240%, p < 0.001) and after 12 months of insulin analogues treatment (9.40% vs 8.38%, p < 0.001). The frequency of severe hypoglycaemia was significantly lower in both groups after 6 months (in the group I from 61.1% to 4.2% and in the group II from 54.4% to 1.3%, p < 0.001), and after 12 months (in the group I from 61.1% to 1.4% and in the group II from 54.4% to 1.3%, p < 0.001).. Significantly better HbA1c values and lower risk of severe hypoglycaemia were established in children and adolescents with T1DM treated with insulin analogues.

Topics: Adolescent; Child; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Retrospective 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

This 26-wk observational study in children and adolescents with type 1 diabetes (T1D) in Sweden investigated the safety and efficacy of insulin detemir (IDet) in newly diagnosed (ND) patients and those with established diabetes (ED) switching to IDet. A total of 159 patients initiated IDet as part of basal-bolus therapy, 59 in the ND stratum (mean age 9.7 yr) and 97 in the ED stratum (mean age 12.5 yr). The primary outcome measure was the incidence of severe adverse drug reactions; just one major hypoglycemic event occurred in a patient in the ND stratum during the study and one patient was withdrawn due to injection-site reactions. All other events were classified as mild. In the ED stratum, there was a reduction in hypoglycemic events in the 4 wk prior to study end from baseline (mean reduction of 2.46 events, not significant) and a significant reduction in nocturnal hypoglycemia (mean reduction of 2.24 events, p = 0.0078). Glycemic control improved in the ND stratum as expected and, in the ED stratum, there was no significant change in HbA1c from baseline (mean reduction of -0.45%). At study end, mean daily IDet doses were 0.39 U/kg (ND) and 0.54 U/kg (ED). Weight increased by 5.7 and 2.0 kg in the ND and ED strata, respectively, and was within the normal limits for growing children. IDet provided good glycemic control and was well tolerated, with a reduced risk of nocturnal hypoglycemia in a heterogeneous cohort of children and adolescents with T1D.

Topics: Adolescent; Blood Glucose; Child; Cohort Studies; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemia; In Vitro Techniques; Insulin Detemir; Insulin, Long-Acting; Sweden

Two drugs commonly used in triple-drug therapy for treatment of a Helicobacter pylori infection, clarithromycin and omeprazole, have rarely been associated with hypoglycemia when given alone. No documented interactions between H. pylori treatment with clarithromycin, amoxicillin, and omeprazole and insulin detemir have been previously reported. This case report describes an 82-year-old man with drug-controlled type 2 diabetes who experienced severe hypoglycemia during treatment for a H. pylori infection in an outpatient setting. His diabetes treatment included 32 units of insulin detemir once/day at bedtime and insulin aspart, determined by carbohydrate intake, 3 times/day with meals. After 5 days of clarithromycin 500 mg twice/day, amoxicillin 500 mg twice/day, and omeprazole 20 mg twice/day for treatment of the H. pylori infection, the patient experienced hypoglycemia and self-discontinued clarithromycin. Insulin detemir was decreased to 15 units and hypoglycemia reoccurred. Insulin detemir was further decreased to 10 units without further symptoms of hypoglycemia for the remainder of the H. pylori treatment. Once treatment was completed, the patient was instructed to resume taking 32 units of insulin detemir once/day. His blood glucose concentration returned to a baseline value, and he denied experiencing further hypoglycemic episodes. Health care practitioners should be aware of this possible drug interaction and anticipate that insulin detemir dosage adjustments may be required during treatment of H. pylori infection to avoid significant adverse events.

Topics: Aged, 80 and over; Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Clarithromycin; Drug Interactions; Drug Therapy, Combination; Helicobacter Infections; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin, Long-Acting; Male; Omeprazole

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

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

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

Insulin overdose can cause harm due to hypoglycaemia, effects on electrolytes and acute hepatic injury. The established long-acting insulin analogue preparations (detemir and glargine) can present specific management problems because, in overdose, their effects are extremely prolonged, often lasting 48-96 hours. The primary treatment is continuous intravenous 10% or 20% glucose infusion with frequent capillary blood glucose monitoring. Surgical excision of the insulin injection site has been used successfully, even days after the overdose occurred. Once the effects of overdose have receded, diabetes treatment must be restarted with care, especially in patients with type 1 diabetes. Monitoring serum insulin concentration has been successfully used to predict when the effects of the overdose will cease.

Topics: Adult; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Drug Overdose; Electrolytes; Glucose; Humans; Hypoglycemia; Infusions, Intravenous; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Sweetening Agents

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

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

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

To estimate short-term cost-effectiveness of insulin detemir vs. NPH insulin based on the incidence of mild hypoglycaemia in subjects with Type 1 diabetes in Denmark, Sweden, Finland and the Netherlands.. A model was developed to evaluate cost-effectiveness based on mild (self-treated) hypoglycaemia and pharmacy costs over 1 year. Published rates of mild hypoglycaemia were used for NPH insulin and insulin detemir. Effectiveness was calculated in terms of quality-adjusted life expectancy. Pharmacy costs were accounted using published prices and defined daily doses for both insulins. Costs were expressed in 2010 euros (€).. Treatment with insulin detemir was associated with fewer mild hypoglycaemic events than NPH insulin (mean rates of 26.3 vs. 35.5 events per person-year), leading to an improvement in mean quality-adjusted life expectancy of approximately 0.019 (0.030) quality-adjusted life years (standard deviation). Annual costs were € 573.55 (110.42) vs. € 332.76 (62.18) in Denmark for insulin detemir and NPH insulin, respectively. These values were € 545.79 (106.54) vs. € 306.12 (57.78) in Sweden, € 720.10 (140.74) vs. € 408.73 (78.61) in Finland and € 584.01 (109.47) vs. € 359.60 (64.84) in the Netherlands. Incremental cost-effectiveness ratios were approximately € 12,644 (Denmark), € 12,612 (Sweden), € 16,568 (Finland) and € 12,216 (the Netherlands) per quality-adjusted life year gained for insulin detemir vs. NPH insulin.. Insulin detemir is likely to be cost-effective vs. NPH insulin in subjects with Type 1 diabetes in Denmark, Sweden, Finland and the Netherlands. Increased pharmacy costs with insulin detemir should not be a barrier to therapy based on these findings.

Topics: Cost-Benefit Analysis; Denmark; Diabetes Mellitus, Type 1; Female; Finland; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Netherlands; Pharmacies; Quality-Adjusted Life Years; Sweden

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

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

Topics: Blood Glucose; Clinical Trials as Topic; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

The liver glucose production (LGP) levels of 15-h overnight fasted weaned rats submitted to short-term insulin-induced hypoglycemia (ST-IIH) and long-term IIH (LT-IIH) were compared. Experiments to characterize ST-IIH or LT-IIH that followed an intraperitoneal (ip) injection (1.0 U/kg) of regular (ST-IIH) or insulin detemir (LT-IIH) were performed and glycemia were measured 0 (normoglycemic control), 0.5 h (ST-IIH), 4 h and 6 h (LT-IIH) later. The values of glycemia (mg/dl) were 77.8 ±l 7.2 (normoglycemic control), 26.2 ±l 6.1 (ST IIH 0.5 h), 21.2 ±l 7.6 (LT-IIH 4 h) and 35.3 ±l 14.5 (LT-IIH 6.0). The LGP levels were measured in the rats submitted to ST-IIH (0.5 h) and LT-IIH (4 h or 6 h). The rats that received ip saline were used as the normoglycemic control group (COG). The livers from the COG and IIH groups (ST-IIH or LT-IIH) were perfused in situ with infusion of L-alanine (5 mM), L-glutamine (10 mM), glutamine dipeptide (5 mM), L-lactate (2 mM) or glycerol (2 mM). The ST-IIH rats showed a higher LGP level than COG group following the L-glutamine infusion (p < 0.05), but the LGP levels that were measured following the L-lactate, L-alanine, glutamine dipeptide (5 mM), L-lactate (2 mM) or glycerol infusion remained unchanged. Moreover, if the period of IIH was expanded to 4 h following insulin injection, the LGP levels induced by L-alanine, glutamine dipeptide or glycerol infusion also increased (p < 0.05, LT-IIH vs. COG). However, the LGP from the L-lactate infusion remained unchanged until 6 h after insulin injection. In conclusion, these results suggest that the intensification of liver gluconeogenesis during ST-IIH and LT-IIH in weaned rats is not a synchronous "all or nothing" process; instead, this process integrated in a temporal manner and is specific for each gluconeogenic substrate.

Topics: Alanine; Animals; Gluconeogenesis; Glucose; Glutamine; Glycerol; Hypoglycemia; Hypoglycemic Agents; Injections, Intraperitoneal; Insulin; Insulin Detemir; Insulin, Long-Acting; Lactic Acid; Liver; Male; Rats; Rats, Wistar; Time Factors

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

The role of glutamine dipeptide (GDP) to prevent against prolonged insulin induced hypoglycemia (IIH) in overnight fasted rats was investigated. The glycemia was measured 0, 2, 4, 8, and 10 h after an intraperitoneal (i.p.) injection (1 U/kg) of Detemir insulin. Because the lowest glycemia was obtained 4 h after insulin administration, the experiments were done at this time. The hypoglycemia obtained 4 h after insulin injection was partially prevented with increasing oral doses of GDP (1.56, 3.12, 6.25, 12.5 mg/kg). The best result was obtained with 12.5 mg/kg. However, from this dose (25.0, 50.0, 100.0 mg/kg), the values of glycemia progressively decreased (p<0.05). The effect of GDP to prevent prolonged IIH was mediated, partly at least, by an intensification of liver gluconeogenesis. Moreover, the increased portal availability of GDP, L-alanine and L-glutamine after GDP administration also contributed to the IIH prevention, since the rate of gluconeogenesis progressively augmented with the infusion of increasing concentrations of these substances. However, after getting the maximal value, the rate of liver gluconeogenesis decreased (p<0.05) if a more elevated concentration of L-alanine or L-glutamine was infused. On the other hand, the liver gluconeogenesis during the infusion of increasing concentrations of GDP was unchanged. Because, GDP did not directly inhibit liver gluconeogenesis, but an inhibition of this metabolic pathway was observed with low ammonia concentrations (from 0.062 mM) it is possible that the ammonia from the catabolism of GDP by extra hepatic tissues could inhibit liver gluconeogenesis. This mechanism could help to explain the lower glycemia obtained with more elevated doses of oral GDP.

Topics: Alanine; Animals; Area Under Curve; Blood Glucose; Dipeptides; Gluconeogenesis; Glutamine; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Liver; Liver Circulation; Male; Rats; Rats, Wistar; Urea

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

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

Insulin detemir (Levemir) is a soluble human insulin analogue acylated with a 14-carbon fatty acid, which reversibly binds to albumin, thereby providing a more prolonged metabolic effect with lower variability as compared to NPH insulin taken as reference. Thanks to this pharmacokinetic and pharmacodynamic profile, insulin detemir is essentially used within a basal-bolus regimen. We report the results obtained in 232 type 1 diabetic patients recruited in Belgium in the frame of the international observational, open, prospective PREDICTIVE study. In patients initially treated with either NPH insulin or glargine, followed for 26 weeks, the shift to insulin detemir did not change HbA1c levels, but significantly reduced both the mean and the variability of fasting blood glucose levels while diminishing the risk of hypoglycaemic episodes, especially at night. Therefore, insulin detemir was associated with significantly improved quality of life. These changes were obtained with a slight increase in daily insulin doses but without weight gain.

Topics: Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemia; Insulin; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged

The insulin analogs, glargine and detemir, are associated with reduced hypoglycemia incidence compared with NPH insulin. We assessed the impact of changing basal insulin from NPH to glargine or detemir in patients with type 1 diabetes mellitus who experienced severe hypoglycemia.. A retrospective chart review was conducted that included 73 (31 female) patients (mean age 48 years, diabetes duration 19 years) treated for 12 to 24 months with insulin glargine (n = 43) or detemir (n = 30).. There were no patients who withdrew from treatment due to side effects. The mean treatment duration in both groups was 18 months. Changing from NPH insulin was associated with a -0.3% (p = 0.036) reduction in HbA1c for glargine (baseline 8.8%) and -0.4% (p = 0.040) for detemir (baseline 8.3%) treated patients; insulin dosages increased, respectively by 4.1 (p = 0.045) and 4.3 units (p = 0.004) (mean values). Weight did not increase significantly and the 1-year rate of serious hypoglycemia was 0.25/person/year.. Switching from NPH-insulin to insulin detemir or glargine in type 1 diabetes mellitus patients with previous serious hypoglycemia was associated with a reduction in HbA1c. However, severe hypoglycemia was not completely eliminated, and few patients reached internationally accepted glycemic treatment goals.. We searched Medline, PubMed (with key search terms type 1 diabetes, NPH insulin, detemir, glargine and serious hypoglycemia), reference lists and databases of ongoing and completed trials (through July 2008) provided from the manufacturers of the drugs to identify relevant literature.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Retrospective Studies; Severity of Illness Index; Treatment Outcome

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

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

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

Iowa Care (Iowa Medicaid), USA, switched insulin glargine to insulin detemir in subjects with diabetes mellitus without the approval of healthcare providers. This study set out to examine the impact of transition on parameters of diabetes management in type 1 diabetes.. This was a retrospective review of the records of subjects with type 1 diabetes up to August 2007 in whom transition occurred. Subjects completing 6 months of insulin detemir therapy were included. Twenty-four subjects switching from insulin glargine to insuline detemir (group 1) fulfilled the duration with insulin detemir. Glycaemic control (glycosylated haemoglobin [HbA1c]), bodyweight, daily insulin dose (units), total and insulin glargine or insulin detemir and rapid-acting insulin aspart and hypoglycaemic events during the last 4 weeks, pre-switch and again at 6 months post-switch were assessed. Records of 21 age-matched subjects and continuing insulin glargine for 6 months (group 2) were examined. Subjects switched from insulin glargine to insulin detemir in the same daily dose. The daily doses of insulin detemir and aspart in group 1 were adjusted by telephone weekly based on blood glucose monitoring until stabilization occurred. Subjects were followed up in the outpatient clinic every 3 months.. Subjects in group 1 changed to insulin detemir twice a day because of a significant rise in hypoglycaemia with the daily dose used once a day. Glycaemic control remained stable on continuing insulin glargine; HbA1c 7.6+/-0.3 to 7.8+/-0.3%, while it worsened on switching to insulin detemir; HbA1c 7.9+/-0.6 to 8.8+/-0.8 despite a higher daily dose; insulin detemir 46+/-9 U/day versus pre-switch insulin glargine 36+/-8 U/day and group 2 insulin glargine 35+/-6 U/day; and greater total insulin dose: 80+/-12 U/day versus 68+/-10 pre-switch and group 2 insulin glargine 62+/-10 U/day (p<0.05 for all comparisons). Bodyweight and hypoglycaemic events were not significantly different pre- and post-switch.. Switching to insulin detemir from glargine is likely to result in lapse of glycaemic control despite a higher daily insulin dose, increased number of injections and need for frequent evaluations.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Monitoring; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Iowa; Male; Medicaid; Retrospective Studies; Therapeutic Equivalency; Time Factors; Treatment Outcome; United States

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

To assess the effect of the insulin analog detemir on glycemic control and severe hypoglycemia in children and adolescents with type 1 diabetes.. A retrospective chart analysis was performed in 105 patients with type 1 diabetes after switching to insulin detemir between 2004 and 2007. In children below 12 yr of age (n = 53), evening neutral protomin hagedorn (NPH) insulin was replaced by insulin detemir if therapeutic goals were not reached and blood glucose levels were unpredictable or hardly controllable. In adolescents above 12 yr of age (n = 52), insulin detemir was started when changing to intensified insulin therapy.. In children below 12 yr of age, hemoglobin A1c (HbA1c) at start was 8.3 +/- 0.8% and after 12 months of treatment with insulin detemir significantly lowered (7.6 +/- 0.6%, p < 0.001). In the age-group above 12 yr of age at the start of the study, the improvement of HbA1c after 12 months of treatment was less pronounced (8.0 +/- 1.2 vs. 7.6 +/- 1.0%) but still significant (p < 0.01). The risk for severe hypoglycemia was significantly decreased compared with patients attending the outpatient clinic between 1995 and 2003 (4.8/100 patient years vs. 7.6/100 patient years, p = 0.003). From the beginning to the end of the follow-up period, body mass index dropped significantly in children below 12 yr of age but no effect was observed in adolescents.. Use of insulin detemir allows a safe nocturnal glycemic control in children and adolescents with type 1 diabetes and is associated with significantly improved HbA1c levels and fewer severe hypoglycemic events. This makes insulin detemir a most valuable new tool for the treatment of children and adolescents with type 1 diabetes.

Topics: Adolescent; Blood Glucose; Child; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Male; Retrospective Studies; Severity of Illness Index

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

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