insulin-detemir and Diabetes-Mellitus--Type-1

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

To compare the safety and efficacy of insulin detemir versus neutral protamine Hagedorn (NPH) in pregnant women with diabetes.. MEDLINE, CENTRAL, Google Scholar databases, and ClinicalTrials.gov registry were searched from inception to December 2021 to identify randomized controlled trials (RCTs) concerning adult women with singleton pregnancies, gestational or pregestational diabetes, and the need for insulin therapy. A systematic review and a meta-analysis (weighted data, random-effects model) were performed. Continuous outcomes were expressed as mean difference (MD) with 95% confidence interval (CI) (inverse variance method); dichotomous outcomes were expressed as risk ratio (RR) with 95% CI (Mantel-Haenszel method). Heterogeneity was quantified using the I. Insulin detemir was associated with less maternal hypoglycemic events and decreased risk for prematurity compared with NPH insulin. More research should be conducted to reach a safe conclusion about the optimal insulin regimen for women with diabetes in pregnancy.

Topics: Adult; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Pregnancy; Protamines; Randomized Controlled Trials as Topic

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Since insulin is the unique and life-long therapy in type 1 diabetes and classical insulin preparations have certain limitations due to their pharmacokinetic and pharmacodynamic properties, the new insulin analogues aim to eliminate these limitations. Five insulin analogues are commercially available and approved for individuals with type 1 diabetes: three rapid-acting (insulin lispro, insulin aspart and insulin glulisine) and two long-acting insulin analogues (insulin glargine and insulin detemir). According to several studies conducted in children with type 1 diabetes, insulin analogues, due to their structural alterations, offer flexibility, reduction of nocturnal hypoglycemic episodes and decrease in postprandial hyperglycemic events, resulting in improved quality of life for diabetic children and their families. However, diabetes control measured with glycosylated hemoglobin A1c has been reported to be similar to conventional insulin preparations. Evidence-based medical reports indicate that insulin analogues are safe and effective, and therefore approved for children even from the age of 2 years. Moreover, suspicions and reports on the association of insulin analogues with carcinogenesis have not been established, requiring further investigation. This review reports the properties and characteristics of insulin analogues, as well as the results of current studies concerning pediatric patients with type 1 diabetes.

Topics: Adolescent; Child; Diabetes Mellitus, Type 1; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting

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

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

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 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Basal bolus insulin dosing (BBD) may be defined as the physiological replacement of basal and bolus insulin to achieve near normal glycemia without hypoglycemia and loss of life quality. Normally, continuous and variable basal insulin release provides partial suppression of hepatic glucose production to maintain euglycemia during the fasting period. With meals, additional insulin is released in a biphasic pattern to further suppress hepatic glucose production and to increase glucose transport into muscle, fat and liver. Newer subcutaneous insulins for bolus and basal mimic near normal secretion. In addition, improvements in continuous subcutaneous insulin infusion pump features such as dual wave insulin delivery allow improved postprandial glycemia. Insulin dosing is done in a three step process. Firstly, the dosage is estimated based on formulas derived from body weight or previous insulin requirements. Secondly, pre-dosing adjustments modify these formulas by considering estimations of insulin sensitivity based on clinical judgment and laboratory evaluations. Lastly, post-dosage adjustments are based on timed, self-monitored, blood glucose determinations assisted by overall average glucose determinations such as hemoglobin A1c. Continuous glucose monitoring systems have provided a more insightful tool for dosage adjustments. Daily consecutive intensive glucose evaluations using a continuous glucose monitoring system and corresponding dosage adjustments may offer an even better tool for insulin dosing selection.

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Fasting; Humans; Injections, Subcutaneous; Insulin; Insulin Detemir; Insulin Secretion; Insulin, Long-Acting; Reference Values

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

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

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

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

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

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

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

Topics: Animals; Blood Glucose; Carrier Proteins; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Solubility

To compare the efficacy and safety of insulin detemir (IDet) versus neutral protamine Hagedorn (NPH) insulin used in pregnant women with diabetes.. A randomized study was conducted in diabetic pregnant women (n=240) (including 132 with pregestational diabetes and 108 with gestational diabetes). All patients were randomly divided into two groups: IDet group (n=120) treated with IDet plus short acting insulin Novolin-R before three meals (RRR-IDet plan), and NPH group treated with NPH plus Novolin-R before three meals (RRR-NPH plan). Patients were enrolled during 12-28 gestation weeks and followed up until delivery.. Basal characteristics, such as age, enrollment gestational weeks, average HbA1c, fasting plasma glucose (FPG) and oral glucose tolerance test (OGTT) were similar between two groups. After 1 week of treatment, the FPG of IDet group were significantly lower than NPH group (p<0.05) and the time required to reach the targeted blood glucose level was significantly shorter (p<0.001). After 3 months of treatment, the HbA1c level in the two groups was normalized but there was no significant difference in HbA1c level. Maternal and neonatal outcomes were comparable between the two therapeutic approaches; however, the incidence of hypoglycemia in IDet group was remarkably lower than that of NPH group (p<0.05). The adverse drug reactions were rare and similar between the two groups.. For the treatment of gestational diabetes, both RRR-IDet plan and RRR-NPH plan were reported to control blood glucose effectively. Compared with NPH, IDet could control blood glucose and reached the targets faster and more effectively, thus reducing the number of insulin injections and the incidence of hypoglycemia in pregnant women without increasing adverse birth outcomes. Therefore, for pregnant women with gestational diabetes, who require insulin therapy, IDet would be an ideal basal insulin being worthy of promotion in clinical settings.

Topics: Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Infant, Newborn; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Pregnancy

With healthcare systems under increasing financial pressure from costs associated with diabetes care, it is important to assess which treatments provide clinical benefits and represent best value. This study evaluated the annual costs of insulin degludec (degludec) versus insulin detemir (IDet) in children and adolescents with type 1 diabetes (T1D) in the UK.. Using data from a randomized, treat-to-target, non-inferiority trial-BEGIN YOUNG 1-annual costs with degludec versus IDet in children and adolescents aged 1-17 years with T1D were estimated, as costs of these insulins and hyperglycemia with ketosis events. Analyses by age group (1-5, 6-11 and 12-17 years) and scenario (no ketosis benefit, no dose benefit, hyperglycemia with ketones >0.6 and >3.0 mmol/L and the additional costs of twice-daily IDet in 64% of patients) were also performed.. The mean annual cost per patient was estimated as £235.16 for degludec vs £382.91 for IDet, resulting in an annual saving of £147.75 per patient. These substantial cost savings were driven by relative reductions in the frequency of hyperglycemia with ketosis and basal insulin dose with degludec versus IDet. Annual savings in favor of degludec were observed across each age group (£122.63, £140.59 and £172.50 for 1-5, 6-11 and 12-17 years age groups, respectively). Five scenario analyses further demonstrated the robustness of the results, which included no ketosis or dose benefits in favor of degludec.. Degludec provides appreciable annual cost savings compared with IDet in children and adolescents with T1D in a UK setting. While a cost-effectiveness analysis could incorporate the health impact of treatment complications better than the present cost analysis, the strong generalizability of the data from this study suggests that degludec can help healthcare providers to maximize health outcomes despite increasingly stringent budgets.

Topics: Adolescent; Biomarkers; Blood Glucose; Child; Child, Preschool; Cost-Benefit Analysis; Diabetes Mellitus, Type 1; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Infant; Insulin Detemir; Insulin, Long-Acting; Male; Prognosis; United Kingdom

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 an additional rapid-acting insulin bolus on postprandial lipaemia, inflammation and pro-coagulation following high-carbohydrate high-fat feeding in people with type 1 diabetes.. Triglyceride concentrations following LF remained similar to baseline, whereas triglyceride levels following HF were significantly greater throughout the 6-h observation period. The additional insulin bolus (HFA) normalised triglyceride similarly to low fat 3-6 h following the meal. HF was associated with late postprandial elevations in tumour necrosis factor alpha, whereas LF and HFA was not. Fibrinogen, plasminogen activator inhibitor-1 and tissue factor pathway levels were similar between conditions.. Additional bolus insulin 3 h following a high-carbohydrate high-fat meal prevents late rises in postprandial triglycerides and tumour necrosis factor alpha, thus improving cardiovascular risk profile.

Topics: Adult; Biomarkers; Blood Coagulation; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 1; Diet, High-Fat; Dietary Carbohydrates; Dietary Fats; England; Humans; Hypoglycemic Agents; Inflammation Mediators; Insulin Detemir; Insulin Glargine; Male; Meals; Postprandial Period; Risk Factors; Time Factors; Treatment Outcome; Triglycerides; Tumor Necrosis Factor-alpha; Young Adult

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 use continuous glucose monitoring (CGM) to compare glycemic variability in patients with type 1 diabetes (T1D) treated with insulin degludec (IDeg) versus insulin detemir (IDet).. Ten patients with T1D were randomly assigned to receive once-daily IDeg, followed by twice-daily IDet, or vice versa. Glucose variability was evaluated by CGM after >4 weeks of the first insulin and again after crossover to the second insulin.. The total daily insulin dose (U/kg/day) and the total daily basal insulin dose (U/kg/day) were significantly lower during treatment with IDeg than with IDet [median (interquartile range): 0.55 (0.54-0.73) vs. 0.64 (0.54-0.83); P = 0.028, 0.24 (0.19-0.36) vs. 0.30 (0.19-0.39); P = 0.027]. The 24-hour mean glucose levels were not significantly different. However, their standard deviation (SD) was significantly smaller during treatments with IDeg than those with IDet [59.5 (39.5-71.0) vs. 72.8 (61.8-92.8); P = 0.008]. Their mean fasting glucose levels and the mean postprandial peak levels after breakfast and after dinner were significantly lower with IDeg.. A CGM-based comparison demonstrated that once-daily IDeg showed fewer glycemic fluctuations than twice-daily IDet. IDeg appears to stabilize blood glucose levels better during both daytime and nighttime (particularly, before and after breakfast) with a lower insulin dosage.

Topics: Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin, Long-Acting; Male; Middle Aged; Pilot Projects; Postprandial Period

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 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

Growth hormone (GH) secretion is increased in pre-pubertal children with type 1 diabetes and GH excess produces insulin resistance. Early-morning insulinopenia contributes to lower insulin-like growth factor (IGF-I) levels and to GH hypersecretion.. To evaluate differences in GH/IGF-I axis of pre-pubertal children with type 1 diabetes treated with glargine or detemir as long-acting insulin analogues, which was the main outcome measure, and to compare insulin effects in obtaining good metabolic control.. Children with type 1 diabetes.. This was a 32-week, randomized, open-label, two-period, cross-over comparison between bedtime glargine and twice-daily detemir insulin, involving pre-pubertal children in care at a diabetes pediatric centre. After a 8-week-run-in period subjects were randomized to bedtime glargine or twice-daily detemir insulin administration. After a 12-week period treatments were inverted and continued for additional 12 weeks.. Overall, 15 pre-pubertal children (53.3% males, mean age 8.6±1.5 years, duration of diabetes 4.2±1.5 years) completed the study. Groups did not differ for GH/IGF axis and HbA1c levels. Treatment with glargine was associated with lower fasting glucose values than treatment with detemir (8.1±1.5 vs. 8.2±1.7 mmol/L, p=0.01). Incidence rate of hypoglycemia was not different between insulin treatments (IRR=1.18, 95%CI 1.00-1.38; p=0.07). Detemir treatment was associated with a higher increase in body weight (p=0.008) and height (p=0.02) when compared with glargine.. Detemir and glargine not show significant differential effects on the GH/IGFI axis. The greater weight gain and height associated with detemir treatment, apparently not related to the level of pubertal growth, deserve further investigation.

Topics: Child; Cross-Over Studies; Diabetes Mellitus, Type 1; Female; Human Growth Hormone; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin-Like Growth Factor I; Male; 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

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

To investigate, using a novel non-steady-state protocol, the differential effects of subcutaneous (s.c.) detemir and NPH insulin on glucose flux and lipid metabolism after insulin withdrawal.. After a period of insulin withdrawal resulting in whole-blood glucose concentration of 7 mmol/l, 11 participants (five men, mean age 41.0 years, mean body mass index 25 kg/m(2)) with type 1 diabetes (mean glycated haemoglobin concentration 57 mmol/mol, mean diabetes duration 14 years) received 0.5 units per kg body weight s.c. insulin detemir or NPH insulin in random order. Stable isotopes of glucose and glycerol were infused intravenously throughout the study protocol.. Glucose concentration decreased after insulin treatment as a result of suppression of endogenous glucose production, which occurred to a similar extent with both detemir and NPH insulin. The rate of glucose disappearance (Rd) was not increased significantly with either type of insulin. When the effect of detemir and NPH insulin on glucose flux at glucose concentrations between 9 and 6 mmol/l was examined, glucose rate of appearance (Ra) was similar with the two insulins; however, glucose Rd was greater with NPH insulin than with detemir at glucose concentrations of 8.0, 8.5, 7.0 and 6.0 mmol/l (p < 0.05) The percentage change in glycerol Ra, a measure of lipolysis, was greater in the NPH group than in the detemir group (p = 0.04).. The results of the study are consistent with the hypothesis that detemir has a lesser effect on the periphery, as evidenced by a lesser effect on peripheral glucose uptake at specific glucose concentrations.

Topics: Adult; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Glycerol; Humans; Hyperglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin Detemir; Insulin, Isophane; Lipolysis; Male

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

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

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

The aim of the present study was to investigate the effects of subcutaneous detemir on glucose flux, lipid metabolism and brain function. Twelve people with type 1 diabetes received, in random order, 0.5 units/kg body weight detemir or NPH insulin. Glucose concentration was clamped at 5 mmol/l then increased to 10 mmol/l. Glucose production rate (glucose Ra), glucose uptake (glucose Rd) and glycerol production (glycerol Ra) were measured with a constant intravenous infusion of [6,6(2) H(2)]glucose and [(2)H(5)]glycerol. Electroencephalography direct current (DC) and alternating current (AC) potentials were measured. While detemir induced similar effects on glucose Ra, glucose Rd and glycerol Ra during euglycaemia compared with NPH, it triggered a distinct negative shift in DC potentials, with a significant treatment effect in frontal cerebrocortical channels (p < 0.001). AC spectral power showed significant differences in theta and alpha frequencies during euglycaemia (p = 0.03). Subcutaneous detemir exerts different effects on brain function when compared with NPH in people with type 1 diabetes. This may be an important mechanism behind the limitation of weight gain with detemir.

Topics: Adult; Blood Glucose; Brain; Cross-Over Studies; Diabetes Mellitus, Type 1; Electroencephalography; Female; Glycerol; Humans; Hypoglycemic Agents; Infusions, Intravenous; Injections, Subcutaneous; Insulin Detemir; Insulin Infusion Systems; Insulin, Isophane; Lipolysis; Male; Weight Gain

This randomized controlled trial aimed to compare the efficacy and safety of insulin detemir (IDet) with neutral protamine Hagedorn (NPH), both with insulin aspart, in pregnant women with type 1 diabetes. The perinatal and obstetric pregnancy outcomes are presented.. Subjects were randomized to IDet (n = 152) or NPH (n = 158) ≤12 months before pregnancy or at 8-12 gestational weeks.. For IDet and NPH, there were 128 and 136 live births, 11 and 9 early fetal losses, and two and one perinatal deaths, respectively. Gestational age at delivery was greater for children from the IDet arm than the NPH arm (treatment difference: 0.49 weeks [95% CI 0.11;0.88], p = 0.012, linear regression). Sixteen children had a malformation (IDet: n = 8/142, 5.6%; NPH: n = 8/145, 5.5%). The incidence of adverse events was similar between treatments.. IDet is as well tolerated as NPH as regards perinatal outcomes in pregnant women with type 1 diabetes and no safety issues were identified.

Topics: Abortion, Induced; Abortion, Spontaneous; Congenital Abnormalities; Diabetes Mellitus, Type 1; Drug Combinations; Female; Fetal Death; Gestational Age; Humans; Hypoglycemic Agents; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Live Birth; Pregnancy; Pregnancy in Diabetics; Pregnancy Outcome; Pregnancy, Ectopic

The pharmacodynamic characteristics of the basal insulin analogues insulin detemir (IDet) and insulin glargine (IGlar) have been examined extensively via euglycaemic clamp studies. However, differences in clamp methodology and in the analysis of clamp data between trials have led to confusion over the duration of action of these two insulins. The aim of this study was to address these ambiguities in the literature by assessing the pharmacodynamic properties of IDet and IGlar over 30 h under single-dose and steady-state conditions using the definitions and procedures previously standardized by Heise and Pieber in 2007.. This was a single-centre, randomized, double-blind, glucose clamp trial involving 36 patients with type 1 diabetes.. The mean duration of action of IDet was 25.9 h, compared with 19.8 h for IGlar after a single-dose (NS), and 23.3 h (IDet) versus 27.1 h (IGlar) at steady-state (p < 0.0001). IDet had a significantly higher area under the curve glucose infusion rate (AUCGIR ) than IGlar over 0-12 h after a single-dose (p = 0.0018). The steady-state AUCGIR for IDet was numerically higher than IGlar over 0-12 h (728 vs. 592 mg/kg, respectively; p = NS), but significantly lower than IGlar at 12-30 h (p = 0.0003).. The duration of action of IDet is 23 h (range: 4.0-30.0), while that of IGlar is 27 h (range: 10.5-29.0) (95% CI: -8.1, 0.6). This suggests both insulins can be used for once-daily dosing, but individual needs must be considered.

Topics: Adolescent; Adult; Area Under Curve; Blood Glucose; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Glucose Clamp Technique; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged

Studies in rodents have demonstrated that insulin in the central nervous system induces satiety. In humans, these effects are less well established. Insulin detemir is a basal insulin analog that causes less weight gain than other basal insulin formulations, including the current standard intermediate-long acting Neutral Protamine Hagedorn (NPH) insulin. Due to its structural modifications, which render the molecule more lipophilic, it was proposed that insulin detemir enters the brain more readily than other insulins. The aim of this study was to investigate whether insulin detemir treatment differentially modifies brain activation in response to food stimuli as compared to NPH insulin. In addition, cerebral spinal fluid (CSF) insulin levels were measured after both treatments. Brain responses to viewing food and non-food pictures were measured using functional Magnetic Resonance Imaging in 32 type 1 diabetic patients, after each of two 12-week treatment periods with insulin detemir and NPH insulin, respectively, both combined with prandial insulin aspart. CSF insulin levels were determined in a subgroup. Insulin detemir decreased body weight by 0.8 kg and NPH insulin increased weight by 0.5 kg (p = 0.02 for difference), while both treatments resulted in similar glycemic control. After treatment with insulin detemir, as compared to NPH insulin, brain activation was significantly lower in bilateral insula in response to visual food stimuli, compared to NPH (p = 0.02 for right and p = 0.05 for left insula). Also, CSF insulin levels were higher compared to those with NPH insulin treatment (p = 0.003). Our findings support the hypothesis that in type 1 diabetic patients, the weight sparing effect of insulin detemir may be mediated by its enhanced action on the central nervous system, resulting in blunted activation in bilateral insula, an appetite-regulating brain region, in response to food stimuli.. ClinicalTrials.gov NCT00626080.

Topics: Appetite Regulation; Blood-Brain Barrier; Body Weight; Brain Mapping; Diabetes Mellitus, Type 1; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Magnetic Resonance Imaging; Photic Stimulation

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

Insulin regulates the GH-IGF1 axis. Insulin analogs differ from human insulin in receptor affinity and possibly liver accessibility. Therefore, we compared the GH-IGF1 axis response with human NPH insulin, insulin detemir, and insulin glargine in patients with type 1 diabetes (T1D).. A total of 17 patients (seven were women) with T1D (age of 42 (24-63) years (mean and range), BMI of 24.7 (19.5-28.3) kg/m(2), HbA1c of 7.2 (6.3-8.0) % (55 (45-64) mmol/mol), T1D duration of 26 (8-45) years) were studied using a randomized, three-period crossover design. Patients received s.c. injections of equal, individual doses of NPH, detemir, and glargine at 1800 h. Plasma glucose, serum total IGF1, bioactive IGF, IGF-binding protein (IGFBPs), and GH were measured hourly for 14 h post-injection.. When compared with the area under the curve (AUC) following NPH and glargine, detemir resulted in the lowest 6-14 h AUC (mean and range) of IGFBP1 (1518 (1280-1800)) vs 1621 (1367-1922) vs 1020 (860-1210) μg/l×h) and GH (17.1 (14.1-20.6) vs 15.4 (12.7-18.6) vs 10.2 (8.5-12.3) μg/l×h), but in the highest AUC of bioactive IGF (3.8 (3.5-4.2) vs 3.7 (3.4-4.0) vs 4.4 (4.1-4.8) μg/l×h) (all P<0.01). These differences were unrelated to plasma glucose. By contrast, profiles of total IGF1, IGFBP2, and IGFBP3 were comparable.. Independent of plasma glucose, a single dose of detemir caused larger suppression in serum IGFBP1 than NPH and glargine, whereas bioactive IGF was higher, thereby explaining the lower GH levels. Thus, detemir appears to be more liver specific than NPH insulin and glargine.

Topics: Adult; Area Under Curve; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Female; Human Growth Hormone; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin Detemir; Insulin Glargine; Insulin-Like Growth Factor Binding Protein 2; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Insulin, Isophane; Insulin, Long-Acting; Linear Models; Male; Middle Aged; Time Factors; Treatment Outcome

To test the hypothesis that insulin detemir, which is associated with less weight gain than other basal insulin formulations, exerts its weight-modulating effects by acting on brain regions involved in appetite regulation, as represented by altered cerebral blood flow (CBF) or cerebral glucose metabolism (CMRglu).. Twenty-eight male type 1 diabetic patients (age 36.9 ± 9.7 years, BMI 24.9 ± 2.7 kg/m(2), A1C 7.5 ± 0.6%) successfully completed a randomized crossover study, consisting of two periods of 12-week treatment with either insulin detemir or NPH insulin, both in combination with prandial insulin aspart. After each treatment period, patients underwent positron emission tomography scans to measure regional CBF and CMRglu.. After 12 weeks, A1C, daily insulin doses, fasting insulin, and blood glucose levels were similar between treatments. Insulin detemir resulted in body weight loss, whereas NPH insulin induced weight gain (between-treatment difference 1.3 kg; P = 0.02). After treatment with insulin detemir relative to NPH insulin, CBF was higher in brain regions involved in appetite regulation, whereas no significant difference in CMRglu was observed.. Treatment with insulin detemir versus NPH insulin resulted in weight loss, paralleled by increased CBF in appetite-related brain regions in the resting state, in men with well-controlled type 1 diabetes. These findings lend support to the hypothesis that a differential effect on the brain may contribute to the consistently observed weight-sparing effect of insulin detemir.

Topics: Adolescent; Adult; Appetite; Brain; Cerebrovascular Circulation; Cross-Over Studies; Diabetes Mellitus, Type 1; Female; Follow-Up Studies; Glucose; Humans; Hypoglycemic Agents; Imaging, Three-Dimensional; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Magnetic Resonance Imaging; Male; Middle Aged; Regional Blood Flow; Retrospective Studies; Young Adult

To compare the pharmacodynamic properties of insulin detemir (detemir) and neutral protamine lispro (NPL) insulin using a euglycaemic glucose clamp.. In a double-blind, crossover study, 30 patients with C-peptide negative type 1 diabetes were randomly assigned to a single dose (0.4 U/kg) of detemir and NPL. Plasma glucose (PG) was normalized with a variable insulin infusion and then decreased stepwise, followed by a euglycaemic clamp at 5.5 mmol/l over 32 h. Duration of action was defined as time from dosing until PG exceeded 8.3 mmol/l for at least 30 min.. Duration of action was similar for detemir [23.0 (range 2.25-32) h] and NPL [22.0 (9.5-32) h], p = 0.55. Using glucose infusion rate (GIR) parameters, detemir showed a flatter pharmacodynamic profile versus NPL: area under the curve, AUC(GIR) ((0-32))  = 1326 vs. 1841 mg/kg, p < 0.01 (detemir vs. NPL, respectively); AUC(GIR) ((0-12))  = 784 vs. 1392 mg/kg, p < 0.05; AUC(GIR) ((12-32))  = 455 vs. 274 mg/kg, p = 0.051; GIR(late) (12-32)/GIR(early) (0-12) ratio = 0.33 vs. 0.04, p < 0.001. Detemir also showed a lower and later peak of action than NPL [GIR(max) 2.0 vs. 3.2 mg/kg/min, p < 0.01; T(max) 9.1 (95% confidence interval: 3.0-14.7) vs. 7.0 h (1.8-15.2)].. Detemir and NPL had similar duration of action of approximately 24 h in patients with type 1 diabetes. Compared with NPL, detemir had a flatter profile with a more even distribution of metabolic effect over 24 h.

Topics: Adult; Area Under Curve; Blood Glucose; Body Mass Index; Cross-Over Studies; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Double-Blind Method; Female; Glucose Clamp Technique; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Male; Protamines

This 52-week, randomized, multinational, open-label, parallel-group, non-inferiority trial investigated the efficacy and safety of basal-bolus treatment with insulin detemir vs. NPH (neutral protamine Hagedorn) insulin, in combination with insulin aspart, in subjects aged 2-16 years with Type 1 diabetes mellitus.. Of the 347 randomized and exposed subjects, 177 received insulin detemir and 170 NPH insulin, both administered once or twice daily in combination with mealtime insulin aspart. Glycaemic measurements and weight were followed over 52 weeks.. After 52 weeks, insulin detemir was shown to be non-inferior to NPH insulin with regard to HbA(1c) [mean difference insulin detemir-NPH: 1.30 mmol/mol, 95% CI -1.32 to 3.92 (0.12%, 95% CI -0.12 to 0.36) in the full analysis set and 1.41 mmol/mol, 95% CI -1.26 to 4.08 (0.13%, 95% CI -0.12 to 0.37) in the per protocol analysis set]. Hypoglycaemic events per subject-year of exposure of 24-h and nocturnal hypoglycaemia were significantly lower with insulin detemir than with NPH insulin (rate ratio 0.76, 95% CI 0.60-0.97, P = 0.028 and 0.62, 95% CI 0.47-0.84, P = 0.002, respectively). Weight standard deviation (sd) scores (body weight standardized by age and gender) decreased with insulin detemir, but increased slightly with NPH insulin (change: -0.12 vs. 0.04, P < 0.001). At end of the trial, median insulin doses were similar in both treatment groups.. Insulin detemir was non-inferior to NPH insulin after 52 weeks' treatment of children and adolescents aged 2-16 years, and was associated with a significantly lower risk of hypoglycaemia, together with significantly lower weight sd score when compared with NPH insulin.

Topics: Adolescent; Blood Glucose; Body Mass Index; Body Weight; Child; Child, Preschool; Diabetes Mellitus, Type 1; Drug Administration Schedule; Europe; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Treatment Outcome

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

Mixing rapid acting insulin analogs with detemir insulin to minimize daily injections has been adopted as a common regimen, especially for some children with type 1 diabetes, despite the manufacturing company's caution against mixing these analogs in the same syringe. The effect of this practice on the pharmacodynamics (PD) of rapid-acting insulin has not been widely studied. This crossover, randomized study was undertaken to determine whether mixing aspart with detemir insulin has an adverse effect on the early glucodynamic action of rapid-acting insulin analog in humans.. Eight adolescents with type 1 diabetes (age 17.3 ± 0.6 years and A1C 7.3 ± 0.3%) had two euglycemic glucose clamps during which 0.2 units/kg aspart and 0.4 units/kg detemir insulin were injected either as a separate or single mixed injection in random order.. Mixing the two insulins diminished the peak and overall early aspart insulin action with significantly lower maximum glucose infusion rate (GIR(max) separate 6.1 ± 0.7 mg/kg/min vs. mix 4.5 ± 0.5 mg/kg/min; P = 0.03) values and the area under curve for GIR during the first 3 h of the insulin action study (separate 757 ± 105 mg/kg vs. mix 491 ± 66 mg/kg; P = 0.04).. These data demonstrate that mixing aspart with detemir insulin markedly lowers the early PD action of aspart and prolongs its time-action profile as compared with the separate injection of these analogs. These changes in insulin PD should be weighed against the added convenience of mixing when considering such unlicensed use of these insulins in youth with type 1 diabetes.

Topics: Adolescent; Blood Glucose; Child; Diabetes Mellitus, Type 1; Drug Combinations; Drug Interactions; Female; Glucose; Humans; Hypoglycemic Agents; Infusion Pumps; Insulin Aspart; Insulin Detemir; Insulin, Long-Acting; Male; Time Factors; Young Adult

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

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

This multicenter observational study was conducted to investigate the efficacy and safety of insulin detemir (detemir) for diabetes management in Japanese children and adolescents.. Data from the Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes database were analyzed. Ninety children (32 boys, 58 girls; mean age, 11.9 ± 3.8 years) who transferred from a neutral protamine Hagedorn insulin or insulin glargine basal-bolus regimen to detemir basal-bolus therapy and who were observed for at least 12 months were identified. Clinical data obtained at 0, 3, 6, and 12 months were analyzed to determine the type of bolus insulin used, number and timing of detemir injections, detemir dose as a proportion of the total insulin dose, hemoglobin A1c (HbA1c), fasting blood glucose (FBG) and frequency of severe hypoglycemia.. Twelve months after switching to detemir, the detemir dose represented 39.8% of the total insulin dose, and 37.8% of patients were being treated with twice-daily injections. HbA1c and FBG were significantly reduced from baseline at 3 and 6 months but not at 12 months. Considering the seasonal HbA1c variation in the Japanese population, a separate analysis was performed using data for 65 children (21 boys, 44 girls; mean age, 11.6 ± 2.9 years) who switched to detemir during the winter. Subset analysis showed significant HbA1c reductions from baseline at all specified times. The incidence of severe hypoglycemia during detemir treatment was 4.4 episodes per 100 patient-years.. Detemir is an effective and safe basal insulin for diabetes management in Japanese children and adolescents.

Topics: Adolescent; Blood Glucose; Child; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin Detemir; Insulin, Long-Acting; Japan; Male; Morbidity; Retrospective Studies; Treatment Outcome

This randomized, controlled noninferiority trial aimed to compare the efficacy and safety of insulin detemir (IDet) versus neutral protamine Hagedorn (NPH) (both with prandial insulin aspart) in pregnant women with type 1 diabetes.. Patients were randomized and exposed to IDet or NPH up to 12 months before pregnancy or at 8-12 weeks gestation. The primary analysis aimed to demonstrate noninferiority of IDet to NPH with respect to A1C at 36 gestational weeks (GWs) (margin of 0.4%). The data were analyzed using linear regression, taking several baseline factors and covariates into account.. A total of 310 type 1 diabetic women were randomized and exposed to IDet (n = 152) or NPH (n = 158) up to 12 months before pregnancy (48%) or during pregnancy at 8-12 weeks (52%). The estimated A1C at 36 GWs was 6.27% for IDet and 6.33% for NPH in the full analysis set (FAS). IDet was declared noninferior to NPH (FAS, -0.06% [95% CI -0.21 to 0.08]; per protocol, -0.15% [-0.34 to 0.04]). Fasting plasma glucose (FPG) was significantly lower with IDet versus NPH at both 24 GWs (96.8 vs. 113.8 mg/dL, P = 0.012) and 36 GWs (85.7 vs. 97.4 mg/dL, P = 0.017). Major and minor hypoglycemia rates during pregnancy were similar between groups.. Treatment with IDet resulted in lower FPG and noninferior A1C in late pregnancy compared with NPH insulin. Rates of hypoglycemia were comparable.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Pregnancy; Pregnancy in Diabetics

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

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

Insulin detemir lacks the usual propensity for insulin to cause weight gain. We investigated whether this effect was a result of reduced energy intake and/or increased energy expenditure.. A 32-week, randomized crossover design trial was undertaken in 23 patients with type 1 diabetes. Patients on a basal-bolus regimen (with insulin aspart as the bolus insulin) were randomly assigned to insulin detemir or NPH insulin as a basal insulin for 16 weeks, followed by the other basal insulin for 16 weeks. At the end of each 16-week period, total energy expenditure, resting energy expenditure, diet-induced thermogenesis, activity energy expenditure, energy intake, weight change, glycemic control, hypoglycemic episodes, and hormones that affect satiety and fuel partitioning were measured.. After 16 weeks, weight change was -0.69±1.85 kg with insulin detemir and +1.7±2.46 kg with NPH insulin (P<0.001). Total energy intake was significantly less with insulin detemir (2,016±501 kcal/day) than with NPH insulin (2,181±559 kcal/day) (P=0.026). There was no significant difference in any measure of energy expenditure, HbA1c percentage, or number of hypoglycemic episodes. Leptin was lower and resistin was higher with insulin detemir compared with NPH insulin (P=0.039, P=0.047). After the meal, ghrelin and pancreatic polypeptide levels (P=0.002, P=0.001) were higher with insulin detemir.. The reduced weight gain with insulin detemir compared with NPH insulin is attributed to reduced energy intake rather than increased energy expenditure. This may be mediated by a direct or indirect effect of insulin detemir on the hormones that control satiety.

Topics: Adult; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Eating; Energy Intake; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Weight Gain

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

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

This study compared the effects of insulin glargine and insulin detemir on blood glucose variability under clinical practice conditions in patients with type 1 diabetes (T1D) using glulisine as the mealtime insulin.. This was a multicenter, crossover trial in 88 randomized T1D patients: 54 men and 34 women, 46.8±13.7 years old, with a duration of diabetes of 18±9 years and hemoglobin A1c level of 7.1±0.7%. The per-protocol population included 78 patients: 44 received glargine/detemir and 34 detemir/glargine in the first/second 16-week period, respectively. The primary end point was the coefficient of variation (CV) of fasting blood glucose (FBG). Secondary end points included variability of pre-dinner blood glucose, mean amplitude of glycemic excursions, mean of daily differences, and doses and number of daily insulin injections. The non-inferiority criterion was an insulin glargine/insulin detemir FBG CV ratio with a 95% confidence interval (CI) upper limit ≤1.25.. The non-inferiority criterion was satisfied with a mean value of 1.016 (95% CI=0.970-1.065). Intention-to-treat analysis confirmed the non-inferiority with a 95% CI upper limit=1.062. No significant differences were found on secondary objectives, but there was a trend to higher doses and number of daily injections with insulin detemir. A total of eight (four glargine and four detemir) patients reported nine serious adverse events (including one severe episode of hypoglycemia). None of them was considered as related to basal insulins. Serious adverse events led to treatment discontinuation in two patients of the detemir group and none in the glargine group.. In T1D patients under clinical practice conditions, insulin glargine was non-inferior to insulin detemir regarding blood glucose variability, as assessed by CV of FBG.

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

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

We hypothesized that insulin detemir mixed with aspart had equivalent effects on blood glucose as if being given as separate injections in pediatric type 1 diabetes patients.. Fourteen children with type 1 diabetes were randomly assigned to either Study A (mixed insulins) or Study B (separate insulins) for the first 10 days and crossed over for the last 10 days. Each subject underwent continuous glucose monitoring on the last 72 h of each study.. The 48-h area under the curve (mmol/hour/l), M-value, and mean amplitude of glucose excursion (mmol/l) for Study A versus Study B were 457 +/- 70 versus 469 +/- 112 (P = 0.58), 39.67 +/- 15.37 versus 39.75 +/- 9.69 (P = 0.98), and 6.35 +/- 1.92 versus 5.98 +/- 0.92 (P = 0.42), respectively.. Insulin detemir mixed with aspart had equivalent effects on blood glucose versus giving them as separate injections in children with type 1 diabetes.

Topics: Adolescent; Blood Glucose; Child; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemic Agents; Injections; Insulin Aspart; Insulin Detemir; Insulin, Long-Acting; Male

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

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

The purpose of this study was to compare effects of insulin detemir once daily versus twice a day in a basal-bolus insulin regimen.. In this open-label, 7-month study, 520 patients with type 1 diabetes were randomly assigned to receive detemir once daily or twice daily with mealtime insulin aspart. Insulin doses were titrated over 1 month, with patients followed up over the subsequent 3 months. Thereafter, patients were able to switch from one regimen to the other, with an additional nonrandomized 3-month follow-up, to a total of 7 months. The primary end point was A1C at 4 months, with noninferiority defined as a difference <0.4% between groups.. A1C at 4 months was 8.1 +/- 0.9 versus 8.0 +/- 1.0% with once- and twice-daily detemir, respectively, with an adjusted between-group difference of 0.12% (95% CI -0.01 to 0.25%), showing noninferiority for once-daily dosing. Similar results were found in the per protocol population. Improvement in A1C was similar in both groups (-0.4 +/- 0.8 vs. -0.5 +/- 0.8%; P = 0.09, NS) but with differences in the 7-point glucose profile. Detemir doses were lower (29 +/- 18 vs. 39 +/- 20 units/day, P < 0.001), but aspart doses were higher (34 +/- 17 vs. 26 +/- 14 IU/day, P < 0.001) with once-daily detemir. At 7 months, A1C decreased slightly in patients switched from once-daily to twice-daily administration (8.2 +/- 0.8 vs. 8.0 +/- 0.8%; P = 0.34, NS) in association with increased total insulin doses (P < 0.05), but A1C increased in those switched from twice-daily to once-daily administration (7.2 +/- 0.9 vs. 7.6 +/- 0.8%, P < 0.05) in association with decreased doses (P < 0.05).. Although some individuals may benefit from twice-daily dosing, the most suitable routine starting schedule for detemir in a basal-bolus regimen for type 1 diabetes is once-daily injection.

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Drug Administration Schedule; Eating; Follow-Up Studies; Glycated Hemoglobin; Humans; Insulin Aspart; Insulin Detemir; Insulin, Long-Acting; Treatment Outcome

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

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 aim of this study was to compare the effects of exercise on plasma glucose excursions when using each of three basal insulins in people with Type 1 diabetes.. This was a multinational, open-label, randomized, three-period, crossover clinical trial. People with Type 1 diabetes [n = 51, age 39 +/- 10 (+/- sd) years, 67% men] managed with mealtime plus basal insulin regimens, were exercised for 30 min, 5 h after the last mealtime and basal insulin injection when using insulin detemir, insulin glargine or neutral protamine Hagedorn (NPH) insulin.. There were no significant differences in the plasma glucose excursions during or for 150 min after exercise. During 30 min exercise, five (11%) participants on insulin detemir developed minor hypoglycaemia, six (12%) for NPH and 18 (38%) for glargine. From the end of exercise to 150 min, five (11%) on insulin detemir developed minor hypoglycaemia, seven (14%) for NPH and nine (19%) for glargine. In total, from start of exercise to 150 min after exercise, 10 (21%) participants on insulin detemir experienced minor hypoglycaemia as compared with 13 (27%) for NPH and 27 (57%) for glargine (P < 0.001 glargine vs. detemir and NPH). Maximum plasma cortisol levels were lower on detemir and NPH than glargine.. Insulin detemir was associated with less hypoglycaemia than insulin glargine but not NPH insulin in relatively well-controlled people with Type 1 diabetes during and after exercise.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Exercise; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome; Young Adult

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 purpose of this study was to compare the efficacy and safety of insulin glargine and detemir with NPH insulin in children and adolescents with type 1 diabetes mellitus (DM).. Thirty four children and adolescents with type 1 DM (mean age 12.7 ± 3.4 years, diabetes duration 5.4 ± 3.0 years) were included in the study. All patients had been receiving intensive insulin therapy with insulin aspart and NPH for at least 6 months before switching from NPH to insulin glargine (Group 1, n=19) or detemir (Group 2, n=15). The medical records obtained within 6 months before and after treatment with insulin glargine and detemir were retrospectively reviewed and the data were compared in each group.. The mean age and duration of DM were similar in two groups (p>0.05). In both groups, switching from NPH to insulin glargine or detemir, resulted in a reduction in HbA(1c) (p0.05, for both). Patients in the detemir treated group had less increment in body mass index (BMI) SDS at the end of 6 months of therapy compared to NPH and glargine treated patients (p>0.05, for both). No side effects were noted throughout the study.. Both insulin glargine and detemir improved HbA(1c) at short-term and proved to be safe and well tolerated in children and adolescents with type 1 DM.

Topics: Adolescent; Blood Glucose; Body Mass Index; Child; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Retrospective Studies; 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

Insulin detemir (detemir) has previously been shown to be associated with lower within-subject variability compared with other basal insulin preparations in adults with type 1 diabetes mellitus (T1DM). This randomized, double-blind, crossover trial compared the within-subject variability of detemir and insulin glargine (glargine) in pharmacokinetic properties in children and adolescents with T1DM. The trial enrolled 32 children and adolescents (19 girls and 13 boys; mean +/- SD: age 13 +/- 2.5 yr and T1DM duration 6.3 +/- 3.0 yr) with a hemoglobin A1c (HbA1c) of 7.9 +/- 1.0%. Participants were randomized to a specific treatment sequence in which a dose of 0.4 U/kg of detemir and glargine was injected subcutaneously 24 h apart at each of two dosing visits. Insulin concentrations were measured at frequent intervals for a period of 16-h post-dosing. Detemir showed statistically significantly less within-subject variability compared with glargine with a 3.1-fold and 2.9-fold lower coefficient of variation (CV, %) for the area under the concentration-time curve [AUC((0-16) (h))] and the maximum concentration (C(max)), respectively. Separate analyses demonstrated a 2.5-fold and 2.9-fold lower CV (%) with detemir in children (8-12 yr) and a 4-fold and 3.8-fold lower CV (%) with detemir in adolescents (13-17 yr). No safety concerns were raised during the trial. In conclusion, within-subject variability in pharmacokinetic properties was significantly lower for detemir than for glargine in children and adolescents with T1DM. This indicates a less variable absorption with detemir, which is expected to be associated with a more predictable therapeutic effect also in this population.

Topics: Adolescent; Child; Cross-Over Studies; Diabetes Mellitus, Type 1; Double-Blind Method; Female; Humans; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male

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 24-month, multi-national, open-label, parallel group trial investigated the long-term efficacy and safety of insulin detemir and Neutral Protamine Hagedorn insulin in combination with mealtime insulin aspart in patients with Type 1 diabetes using a treat-to-target concept.. Patients were randomized 2 : 1 to detemir (n = 331) or NPH (n = 166) groups. Basal insulin was initiated once daily (evening) and titrated individually based on self-measured plasma glucose (PG) levels, aiming for pre-breakfast and pre-dinner targets < or = 6.0 mmol/l. A second basal morning dose could be added according to pre-defined criteria.. After 24 months, superiority of glycated haemoglobin (HbA(1c)) was achieved with detemir compared to NPH (detemir 7.36%, NPH 7.58%, mean difference -0.22% points) [95% confidence interval (CI) -0.41 to -0.03%], with reductions of 0.94% and 0.72% points, respectively. Fasting PG (FPG(lab)) was also lower with detemir (detemir 8.35 mmol/l, NPH 9.43 mmol/l; P = 0.019). Twenty-two per cent of patients treated with detemir reached an HbA(1c) < or = 7.0% in the absence of confirmed hypoglycaemia during the last month of treatment vs. 13% on NPH (P = 0.019). Risk of major and nocturnal hypoglycaemia was 69% and 46% lower with detemir than with NPH (P < 0.001), respectively; patients treated with detemir gained less weight (detemir 1.7 kg, NPH 2.7 kg; P = 0.024). The overall safety profile was similar in the two groups and treatment with detemir did not result in any unexpected findings.. Long-term treatment with the insulin analogues detemir + aspart was superior to NPH + aspart in reducing HbA(1c), with added benefits of less major and nocturnal hypoglycaemia and less weight gain.

Topics: Adolescent; Adult; Aged; Antibodies; Blood Glucose; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Treatment Outcome; Weight Gain

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

To compare pharmacokinetics and pharmacodynamics of insulin analogs glargine and detemir, 24 subjects with type 1 diabetes (aged 38 +/- 10 years, BMI 22.4 +/- 1.6 kg/m2, and A1C 7.2 +/- 0.7%) were studied after a 2-week treatment with either glargine or detemir once daily (randomized, double-blind, crossover study).. Plasma glucose was clamped at 100 mg/dl for 24 h after subcutaneous injection of 0.35 unit/kg. The primary end point was end of action (time at which plasma glucose was >150 mg/dl).. With glargine, plasma glucose remained at 103 +/- 3.6 mg/dl up to 24 h, and all subjects completed the study. Plasma glucose increased progressively after 16 h with detemir, and only eight subjects (33%) completed the study with plasma glucose <180 mg/dl. Glucose infusion rate (GIR) was similar with detemir and glargine for 12 h, after which it decreased more rapidly with detemir (P < 0.001). Estimated total insulin activity (GIR area under the curve [AUC](0-end of GIR)) was 1,412 +/- 662 and 915 +/- 225 mg/kg (glargine vs. detemir, P < 0.05), with median time of end of action at 24 and 17.5 h (glargine vs. detemir, P < 0.001). The antilipolytic action of detemir was lower than that of glargine (AUC free fatty acids(0-24 h) 11 +/- 1.7 vs. 8 +/- 2.8 mmol/l, respectively, P < 0.001).. Detemir has effects similar to those of glargine during the initial 12 h after administration, but effects are lower during 12-24 h.

Topics: Adult; Area Under Curve; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Double-Blind Method; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged

This study was conducted to evaluate the dose ratio of insulin detemir and neutral protamine Hagedorn (NPH) insulin over a range of therapeutically relevant subcutaneous doses.. The study was a randomized, double-blind, crossover 24-h-iso-glycemic clamp trial in 12 C-peptide-negative type 1 diabetic patients. Each subject received, by an incomplete block design selection, two of three possible doses of insulin detemir (0.15, 0.3, 0.6 U/kg) and NPH insulin (0.15, 0.3, 0.6 IU/kg), respectively. A detailed assessment of endogenous glucose production (EGP) and glucose uptake was performed, by use of stable isotopic labeled glucose tracer (D-[6,6- (2)H (2)] glucose).. Dose proportionality was observed within the tested dose range. Regarding unit dose ratio, 0.68 U insulin detemir equals 1 IU NPH insulin (95% CI [0.35; 1.30]). There was no statistically significant difference in effect on the area under the curve (AUC) of glucose infusion rate (GIR) (AUC (GIR)) and the maximal GIR (GIR (max)) values, when comparing U (insulin detemir) to IU (NPH insulin). The pharmacodynamic within-subject profile was lower with insulin detemir in regard to AUC (GIR 0-24 h), GIR (max) and duration of action ( P<0.05). There was a tendency for a greater reduction of EGP with insulin detemir than with NPH insulin in regard to the area over the curve (AOC) of EGP in 24 hours (AOC (EGP 0-24 h)) ( P=0.07) and minimal EPG (EGP (min)) ( P=0.02).. These data show that insulin detemir is dose-proportional to NPH insulin in type 1 diabetic patients at clinically relevant doses. The data indicate that insulin detemir has a lower degree of within-subject variability.

Topics: Adult; Area Under Curve; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Double-Blind Method; Female; Glucose; Humans; Injections, Subcutaneous; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged

This study investigated the pharmacodynamic and pharmacokinetic characteristics of the novel long-acting insulin analogue insulin detemir (IDet) under single-dose and steady-state conditions in comparison with those of NPH insulin at steady state.. Twenty-five subjects with Type 1 diabetes [seven females, 18 males, mean age (+/- sd) 39 +/- 12 years, body mass index 24 +/- 3 kg/m(2)] participated in three 24-h glucose clamps. IDet or NPH were given at 12-h intervals in fixed, individualized doses. The first clamp assessed the metabolic effect of NPH at steady state, the second investigated the effect of two single injections of IDet. Subjects continued IDet treatment for 7-14 days, after which the third clamp was performed to investigate IDet at steady state.. At steady state, the metabolic effect of IDet was constant over 24 h while a clear peak in the metabolic effect [expressed as glucose infusion rates (GIR)] was observed with NPH after each injection. The fluctuation in the metabolic effect (maximum GIR divided by the average of the GIR values at the interval ends) was significantly lower in the second 12 h of the experiments with IDet under steady-state conditions compared with NPH (fluctuation(12-24 h) 1.27 +/- 0.17 vs. 1.56 +/- 0.72, P < 0.05). The overall metabolic effect of IDet at steady state was comparable with that of NPH [GIR-area under curve (AUC)(0-24 h): 5697 +/- 1861 vs. 5929 +/- 1965 mg/kg] whereas a significantly lower effect (5187 +/- 1784 mg/kg, P = 0.01 vs. steady state) was observed following the first two IDet injections. GIR values at the end of clamp day 2 (first doses) and clamp day 3 (steady state) were comparable [GIR(trough 24 h) 3.7 +/- 1.7 vs. 3.8 +/- 1.6 mg/(kg x min) NS], indicating that IDet had reached steady state after the first two injections.. IDet administered twice daily reached steady state after the second injection and showed a constant metabolic effect over time under steady-state conditions. This should facilitate basal insulin substitution and decrease the risk of hypoglycaemia in insulin-treated subjects.

Topics: Adult; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Glucose; Glucose Clamp Technique; Humans; Hypoglycemic Agents; Infusions, Parenteral; Injections; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male

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

The aim of this study was to compare the long-term safety and efficacy of twice-daily insulin detemir or NPH insulin as the basal component of basal-bolus therapy in people with type 1 diabetes.. A multicentre, open-label, parallel-group study was conducted over 12 months and completed by 308 people (from an original randomized cohort of 428). Patients were randomized in a 2:1 ratio to receive insulin detemir or NPH insulin before breakfast and dinner, with insulin aspart at mealtimes.. Glycaemic control improved in both groups with HbA(1c) decreasing by 0.64 and 0.56% point in the insulin detemir and NPH insulin groups, reaching baseline-adjusted final values of 7.53 +/- 0.10% and 7.59 +/- 0.13%, respectively. No significant difference was apparent between treatments in terms of HbA(1c), fasting plasma glucose or 9-point blood glucose profiles. Fewer hypoglycaemic events (major and minor) occurred in association with insulin detemir compared with NPH insulin, but the overall hypoglycaemic risk did not differ statistically significantly (RR for detemir, 0.78 [0.56-1.08]). However, the risk of nocturnal hypoglycaemia during the maintenance phase (month 2-12) was 32% lower in the detemir group (p = 0.02) and lower in every month. This risk reduction remained statistically significant after correction for HbA(1c). After 12 months, baseline-adjusted mean body weight was significantly lower in the insulin detemir group than in the NPH insulin group (p < 0.001).. In long-term basal-bolus therapy, insulin detemir with insulin aspart as mealtime insulin is well tolerated and reduces the risks of nocturnal hypoglycaemia and weight gain compared to NPH insulin.

Topics: Adult; Blood Glucose; Body Weight; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male

To investigate the pharmacodynamic profile and duration of action for five subcutaneous doses of insulin detemir (0.1, 0.2, 0.4, 0.8, and 1.6 units/kg; 1 unit = 24 nmol) and one subcutaneous dose of NPH insulin (0.3 IU/kg; 1 IU = 6 nmol).. This single-center, randomized, double-blind, six-period, crossover study was carried out as a 24-h isoglycemic clamp (7.2 mmol/l) in 12 type 1 diabetic patients.. Duration of action for insulin detemir was dose dependent and varied from 5.7, to 12.1, to 19.9, to 22.7, to 23.2 h for 0.1, 0.2, 0.4, 0.8, and 1.6 units/kg, respectively. Interpolation of the dose-response relationships for AUC(GIR) (area under the glucose infusion rate curve) revealed that a detemir dose of 0.29 units/kg would provide the same effect as 0.3 IU/kg NPH but has a longer duration of action (16.9 vs. 12.7 h, respectively). Lower between-subject variability was observed for insulin detemir on duration of action (0.4 units/kg insulin detemir vs. 0.3 IU/kg NPH, P < 0.05) and GIR(max) (maximal glucose infusion rate) (0.2 and 0.4 units/kg insulin detemir vs. 0.3 IU/kg NPH, both P < 0.05). Assessment of endogenous glucose production (EGP) and peripheral glucose uptake (PGU) resulted in an AOC(EGP) (area over the EGP curve) of 636 mg/kg (95% CI 279-879) vs. 584 (323-846) and an AUC(PGU) (area under the PGU curve) of 173 (47-316) vs. 328 (39-617) for 0.29 units/kg detemir vs. 0.3 IU/kg NPH, respectively.. This study shows that insulin detemir provides a flat and protracted pharmacodynamic profile.

Topics: Adolescent; Adult; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Double-Blind Method; Fatty Acids, Nonesterified; Female; Glucose; Glucose Clamp Technique; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male

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

Insulin detemir is a soluble long-acting basal insulin analog designed to overcome the limitations of conventional basal insulin formulations. Accordingly, insulin detemir has been compared with NPH insulin with respect to glycemic control (HbA1c, prebreakfast glucose levels and variability, and hypoglycemia) and timing of administration.. People with type 1 diabetes (n = 408) were randomized in an open-label, parallel-group trial of 16-week treatment duration using either insulin detemir or NPH insulin. Insulin detemir was administered twice daily using two different regimens, either before breakfast and at bedtime (IDet(morn+bed)) or at a 12-h interval (IDet(12h)). NPH insulin was administered before breakfast and at bedtime. Mealtime insulin was given as the rapid-acting insulin analog insulin aspart.. With both insulin detemir groups, clinic fasting plasma glucose was lower than with NPH insulin (IDet(12h) vs. NPH, -1.5 mmol/l [95% CI -2.51 to -0.48], P = 0.004; IDet(morn+bed) vs. NPH, -2.3 mmol/l (-3.32 to -1.29), P < 0.001), as was self-measured prebreakfast plasma glucose (P = 0.006 and P = 0.004, respectively). The risk of minor hypoglycemia was lower in both insulin detemir groups (25%, P = 0.046; 32%, P = 0.002; respectively) compared with NPH insulin in the last 12 weeks of treatment, this being mainly attributable to a 53% reduction in nocturnal hypoglycemia in the IDet(morn+bed) group (P < 0.001). Although HbA1c for each insulin detemir group was not different from the NPH group, HbA1c for the pooled insulin detemir groups was significantly lower than for the NPH group (mean difference -0.18% [-0.34 to -0.02], P = 0.027). Within-person between-day variation in self-measured prebreakfast plasma glucose was lower for both detemir groups (both P < 0.001). The NPH group gained weight during the study, but there was no change in weight in either of the insulin detemir groups (IDet(12h) vs. NPH, -0.8 kg [-1.44 to -0.24], P = 0.006; IDet(morn+bed) vs. NPH, -0.6 kg [-1.23 to -0.03], P = 0.040).. Overall glycemic control with insulin detemir was improved compared with NPH insulin. The data provide a basis for tailoring the timing of administration of insulin detemir to the individual person's needs.

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

The aim of this randomized double-blind study was to compare the within-subject variability of the glucose-lowering effect of a novel insulin analog, insulin detemir, with that of insulin glargine and NPH insulin in people with type 1 diabetes. Fifty-four subjects (32 males and 22 females, age 38 +/- 10 years [mean +/- SD], BMI 24 +/- 2 kg/m(2), HbA(1c) 7.5 +/- 1.2%, diabetes duration 18 +/- 9 years) participated in this parallel group comparison. Each subject received four single subcutaneous doses of 0.4 units/kg of either insulin detemir (n = 18), insulin glargine (n = 16), or human NPH insulin (n = 17) under euglycemic glucose clamp conditions (target blood glucose concentration 5.5 mmol/l) on four identical study days. The pharmacodynamic (glucose infusion rates [GIRs]) and pharmacokinetic (serum concentrations of insulin detemir, human insulin, and insulin glargine) properties of the basal insulin preparations were recorded for 24 h postdosing. Insulin detemir was associated with significantly less within-subject variability than both NPH insulin and insulin glargine, as assessed by the coefficient of variation (CV) for the pharmacodynamic end points studied [GIR-AUC((0-12 h)) 27% (detemir) vs. 59% (NPH) vs. 46% (glargine); GIR-AUC((0-24 h)) 27 vs. 68 vs. 48%; GIR(max) 23 vs. 46 vs. 36%; P < 0.001 for all comparisons]. Insulin detemir also provided less within-subject variability in the pharmacokinetic end points: maximal concentration (C(max)) 18 vs. 24 vs. 34%; INS-AUC((0- infinity )) 14 vs. 28 vs. 33%. The results suggest that insulin detemir has a significantly more predictable glucose-lowering effect than both NPH insulin and insulin glargine.

Topics: Adult; Carrier Proteins; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Double-Blind Method; Female; Glucose; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Time Factors; Treatment Outcome

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 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

This trial aimed to characterize for the first time the pharmacokinetic profile of insulin detemir, the novel soluble basal insulin analog, in children and adolescents compared with adults. Comparisons were also made with NPH insulin to determine any between-treatment difference in the effect of age on pharmacokinetic profile.. This single-center, open-label, randomized, crossover trial included children (aged 6-12 years, n = 13), adolescents (aged 13-17 years, n = 10), and adults (aged 18-65 years, n = 11) of both sexes. Subjects were given single doses of 0.5 units/kg s.c. insulin detemir or 0.5 IU/kg NPH insulin on 2 separate days. Serial blood sampling was performed for 24 h for analysis of serum insulin detemir, human insulin, and glucose concentrations.. The mean pharmacokinetic profile of insulin detemir was similar across all three age-groups. This was determined by statistical analyses of the data, which showed no overall age effect or between-group differences when pairwise comparisons were made between children (or adolescents) and adults on the parameters of the area under the curve (AUC), AUC from zero to infinity, AUC from 0 to 24 h [AUC((0-24 h))], and the maximum concentration measured during the 24 h after closing. No overall age effect for AUC((0-24 h)) and C(max) was detected for NPH insulin, but data were only analyzable from seven adults and pairwise comparisons did indicate that children and adults had different pharmacokinetic profiles. Less total variability in the pharmacokinetics of insulin detemir than NPH insulin was indicated by lower coefficients of variation in AUC, C(max), and time to maximum concentration in all three age-groups.. The data suggest that insulin detemir can be used in children and adolescents with type 1 diabetes using titration guidelines similar to those used in adults. Moreover, insulin detemir may offer the advantage of greater predictability of response in comparison to NPH insulin due to lower total variability and a lesser degree of kinetic disparity across age-groups.

Topics: Adolescent; Adult; Age Factors; Aged; Carrier Proteins; Child; Cross-Over Studies; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged

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

A comparative analysis of clinical and laboratory parameters was carried out in 49 children. The patients were divided into 3 groups depending on the type of insulin they received. Group 1 included 20 children who used Insulin human (Insulatard), group 2 included 15 children using insulin Glargine, and group 3 included 14 children using insulin Detemir. All children using Detemir and Glargine used short acting insulin Aspart. Those using Insulin human (Insulatard) used Human insulin (rDNA, Actrapid) in addition. In all children, blood glucose, glycohemoglobin and cholesterol were determined by laboratory methods. Statistical calculations were carried out using a statistical package at a confidence level of p＜0.05. A significant difference was found between the mean values of glycohemoglobin and glucose of Glargine users and patients with using Insulin human (Insulatard) (p≺0.05). These indicators were lower in Glargine users. There is a positive correlation between doses of Regular insulin and Insulin human (Insulatard) with body weight and height. There is a positive correlation between dose of Detemir and body mass. However, no such relationship between Glargine, body mass and height was recorded. It was a negative correlation between its dose Glargine with glycohemoglobin and also between glucose and cholesterol using Glargine.

Topics: Blood Glucose; Child; Diabetes Mellitus, Type 1; Glucose; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Isophane Insulin, Human

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Pregnancy; Protamines

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Pregnancy; Protamines

Topics: Deglutition Disorders; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Detemir; Middle Aged; Respiratory Aspiration; Respiratory Insufficiency

Available basal insulin regimes differ in pharmacokinetic profiles, which may be related to subsequent changes in anthropometry in patients with type 1 diabetes. This analysis elucidates the standardized height and body mass index development (height and BMI standard deviation score [height-SDS and BMI-SDS]) in pediatric type 1 diabetes patients depending on the choice of basal insulin.. Longitudinal data of 10 338 German/Austrian patients from the Diabetes Prospective Follow-up (DPV, Diabetes Patienten Verlaufsdokumentation) database were analyzed. Patients aged 5.0 to 16.9 years were treated exclusively with neutral protamine Hagedorn (NPH), insulin detemir (IDet), insulin glargine (IGla), or continuous subcutaneous insulin infusion (CSII) for at least 3 years. Population-based German reference data were used to calculate height-SDS and BMI-SDS. Multiple linear regression was conducted.. BMI-SDS increased significantly in all regimes (NPH P = .0365; IDet P = .0003; IGla P < .0001; and CSII P < .0001). Direct comparison of the therapies revealed a favorable association only for NPH vs IGla. A rise in BMI-SDS was observed for all insulins in females, but only for IGla in males. BMI-SDS increment was not observed before 8 years of age. Initially and at the end of the observation period, mean height was above the 50th percentile of the reference population. Across the cohort, height-SDS declined during the observation period, except for CSII. Apart from the 5.0- to 7.9-year-old subgroup, long-acting insulin analogues were associated with a significant loss of height-SDS.. Choice of basal insulin regimen might influence height development. CSII appeared to have a favorable effect on growth trajectories. All therapies were associated with an increase of BMI-SDS, most evident in females.. 背景: 现有的基础胰岛素方案在药代动力学方面存在差异, 这可能与1型糖尿病患者后续的人体测量学变化有关。这项分析阐明了儿童1型糖尿病患者基于基础胰岛素的选择的标准化身高和体重指数BMI(身高和BMI标准差评分[身高-SDS和BMI-SDS])的发展。 方法: 对10338例德国/奥地利糖尿病进行前瞻性数据库中的纵向资料进行分析。年龄5.0~16.9岁的患者接受中性鱼精蛋白Hagedorn(NPH), 地特胰岛素(IDET), 甘精胰岛素(IGLA)或持续皮下胰岛素输注(CSII)治疗至少3年。以人群为基础的德国参考数据被用来计算身高-SDS和BMI-SDS。进行多元线性回归分析。 结果: BMI-SDS在所有方案中均显著升高(NPH P=.0365, IDET P=.0003, IGLA P<.0001, CSII P<.0001)。对这些疗法的直接比较显示, 仅对NPH和IGLA有有利的关联。在女性中观察到所有胰岛素的BMI-SDS升高, 但只在男性中观察到IGLA的升高。BMI-SDS在8岁前未见明显增加。 最初和在观察期结束时, 平均身高高于参考人口的第50个百分位数。在整个队列中, 除CSII外, 身高-SDS在观察期内均呈下降趋势。除了5.0到7.9岁的亚组外, 长效胰岛素类似物与身高-SDS显著降低相关。 结论: 基础胰岛素方案的选择可能影响身高发育。CSII似乎对增长轨迹有有利的影响。所有的治疗都与BMI-SDS的增加有关, 这在女性中最为明显。.

Topics: Adolescent; Austria; Biomarkers; Blood Glucose; Body Mass Index; Child; Child, Preschool; Diabetes Mellitus, Type 1; Female; Follow-Up Studies; Germany; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Longitudinal Studies; Male; Prognosis; Prospective Studies; Registries

Type 1 diabetes mellitus (T1DM) is rare in infants and toddlers and is usually associated with a relatively high mortality when complicated with diabetic ketoacidosis (DKA). In infants, the classical symptoms of DKA are atypical and therefore many infants with DKA are mistreated for infections. We report a case of DKA precipitated by COVID-19 in an 8-month-old infant with newly diagnosed diabetes mellitus. This case is reported in view of its rarity and originality. The relation between T1DM and COVID19 infection is discussed.

Topics: Betacoronavirus; Biomarkers; Blood Glucose; Coronavirus Infections; COVID-19; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Humans; Hypoglycemic Agents; Infant; Insulin Detemir; Male; Pandemics; Pneumonia, Viral; SARS-CoV-2

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

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

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

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

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

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

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

Topics: Child; Diabetes Mellitus, Type 1; Humans; Hypoglycemic Agents; Insulin Detemir

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

This study aims to compare glycemic control of persons with type 1 diabetes using multiple daily injections (MDI) with insulin glargine versus insulin detemir or with continuous subcutaneous insulin infusion (CSII) in daily practice.. Altogether, 47.7% used glargine, 43.9% used detemir, and 8.4% used CSII. The mean HbA1c was lower in the CSII group (63 mmol/mol [7.9%]) compared with the glargine group (66 mmol/mol [8.2%]) or the detemir group (67 mmol/mol [8.3%]). The overall rate of DKA was 5.1% per year. The rate of DKA was higher in the detemir group compared with the glargine group (6.3% per year vs. 3.8% per year, respectively, P < 0.049). In logistic regression analyses, the higher rate of DKA with detemir use was explained by HbA1c.. In daily practice, the glycemic control of type 1 diabetes patients with MDI was similar regardless of basal insulin, glargine, or detemir, whereas CSII allowed better glycemic control than MDI. The rate of DKA was higher with detemir than with glargine, but this is likely related to higher HbA1c rather than insulin regimen.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin Infusion Systems; Male; Middle Aged; Treatment Outcome

To identify distinct longitudinal patterns of body mass index (BMI) z score in type 1 diabetes from childhood to young adulthood and secondly to determine sex differences as well as associated clinical covariates.. A total of 5665 patients with type 1 diabetes (51% male) with follow-up from 8 to 20 years of age from the multicenter diabetes prospective registry DPV were studied (baseline diabetes duration ≥1 years, BMI z score aggregated per year of life). Latent class growth modeling (SAS: PROC TRAJ) was applied to analyze BMI z score over time.. Six distinct BMI z score trajectories were identified (group 1: 7% of patients, group 2: 22%, group 3: 20%, group 4: 16%, group 5: 25%, and group 6: 10%). Group 1, 2, 5, and 6 had an almost stable BMI z score, either in the low, near-normal, high stable, or chronic overweight range. Group 3 (60% girls) increased their BMI during puberty, whereas group 4 (65% boys) had a BMI decrease. Similar patterns were observed for girls only, whereas boys followed nearly stable trajectories without fluctuation over time. Between the near-normal and the other groups, significant differences (P < .05) in sex ratio, migration background, mental health, height z score, glycated hemoglobin A1c, diabetes treatment, dyslipidemia, hypertension, and smoking were observed.. In youth with type 1 diabetes, a great heterogeneity of BMI z score trajectories exists that highlight the importance of personalized sex-specific intervention programs for subjects at risk for unfavorable BMI development.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Body Height; Body Mass Index; Child; Diabetes Mellitus, Type 1; Dyslipidemias; Europe; Feeding and Eating Disorders; Female; Glycated Hemoglobin; Humans; Hypertension; Hypoglycemic Agents; Insulin Detemir; Male; Puberty; Registries; Sex Factors; Transients and Migrants; Young Adult

To assess the cost-effectiveness of basal insulin regimens for adults with type 1 diabetes mellitus in England.. A cost-utility analysis was conducted in accordance with the National Institute for Health and Care Excellence reference case. The UK National Health Service and personal and social services perspective was used and a 3.5% discount rate was applied for both costs and outcomes. Relative effectiveness estimates were based on a systematic review of published trials and a Bayesian network meta-analysis. The IMS CORE Diabetes Model was used, in which net monetary benefit (NMB) was calculated using a threshold of £20,000 per quality-adjusted life-year (QALY) gained. A wide range of sensitivity analyses were conducted.. Insulin detemir (twice daily) [iDet (bid)] had the highest mean QALY gain (11.09 QALYs) and NMB (£181,456) per patient over the model time horizon. Compared with the lowest cost strategy (insulin neutral protamine Hagedorn once daily), it had an incremental cost-effectiveness ratio of £7844/QALY gained. Insulin glargine (od) [iGlarg (od)] and iDet (od) were ranked as second and third, with NMBs of £180,893 and £180,423, respectively. iDet (bid) remained the most cost-effective treatment in all the sensitivity analyses performed except when high doses were assumed (>30% increment compared with other regimens), where iGlarg (od) ranked first.. iDet (bid) is the most cost-effective regimen, providing the highest QALY gain and NMB. iGlarg (od) and iDet (od) are possible options for those for whom the iDet (bid) regimen is not acceptable or does not achieve required glycemic control.

Topics: Adult; Bayes Theorem; Blood Glucose; Computer Simulation; Cost-Benefit Analysis; Diabetes Mellitus, Type 1; England; Female; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Male; Middle Aged; Models, Economic; Quality-Adjusted Life Years; Young Adult

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

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

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

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

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 compare glycemic control, maternal-neonatal outcomes and fetal fat body mass growth of type 1 diabetic pregnant women treated with continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI) with the long-acting insulin analogue detemir as basal insulin.. Retrospective study of 53 women, attending the Unit of Prenatal Medicine of Careggi University Hospital, Florence, from 2009 to 2012: 35 treated with CSII, 18 with MDI-detemir. Each woman performed daily blood glucose self-monitoring, had an individualized nutritional therapy, weekly prenatal visits and ultrasound scans (US) according to the Tuscan guidelines. US were also performed every two weeks from 28 to 38 weeks of gestation to assess fetal fat body mass growth. Student's t-test and Chi-square test were performed to compare the groups' results.. No significant differences were observed in metabolic control, in any maternal and neonatal outcome nor fetal fat body mass growth for either group. The MDI group needed higher daily doses of insulin (MDI: 1.00 ± 0.32 UI/kg versus CSII: 0.75 ± 0.29 UI/kg, p = 0.007) to reach results comparable to the CSII group.. MDI therapy with detemir is a safe and effective alternative, with a good benefit-cost ratio compared to insulin pumps.

Topics: Adult; Cost-Benefit Analysis; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemic Agents; Infusions, Subcutaneous; Injections, Subcutaneous; Insulin Detemir; Insulin Infusion Systems; Pregnancy; Retrospective Studies

We aimed to compare hemoglobin A1c (HbA1c), total and basal insulin doses, basal insulin injection frequencies, and body mass index (BMI) in children with type 1 diabetes mellitus (T1DM) who are receiving detemir and glargine as basal insulin in a basal-bolus therapy.. This retrospective study included 117 (53 females) children and adolescents with T1DM older than 4 yr of age, minimum diabetes duration of 2 yr, and receiving basal-bolus insulin regimen (at least 4 injections/d, insulin aspart or lispro as bolus insulin). Comparisons were made for those receiving insulin detemir (n = 32) or glargine (n = 85) as the basal insulin.. Age, pubertal status, BMI standard deviation scores, and diabetes duration were similar in detemir and glargine groups. Glycemic control was similar in both groups (HbA1c levels 8.9 ± 2.1% vs. 8.5 ± 1.7% for detemir and glargine, respectively; p = 0.497). Both mean basal insulin (0.52 vs. 0.41 U/kg/d, p < 0.001) and mean total daily insulin (1.11 vs. 0.93 U/kg/d, p < 0.001) doses were higher in the detemir group. Furthermore, higher ratio of twice-daily basal insulin injection was detected in the detemir group (62.5 vs. 32.9% p = 0.004). Subgroup analysis according to pubertal status, or the number of daily basal injections showed similar results.. Insulin detemir provides similar glycemic control with glargine, but, approximately 27% higher mean basal and 19% higher mean total insulin doses with two-fold more twice-daily basal insulin injection requirement.

Topics: Adolescent; Blood Glucose; Child; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Injections; Insulin Detemir; Insulin Glargine; Male; Retrospective Studies; Treatment Outcome

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

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

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

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

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

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

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

Monitoring of blood glucose concentration is important to evaluate the diabetic status of dogs. Continuous glucose monitoring systems (CGMS) have been applied in veterinary medicine for glucose monitoring in diabetic dogs. The purpose of the study was to evaluate the daily glycemic profiles obtained with CGMS and compare glucose fluctuations between day- and night-time in diabetic dogs. Five diabetic dogs were used in this study and were treated with either NPH insulin or insulin detemir. For data analyses, day-time was defined as 9:00 am-9:00 pm and night-time as 9:00 pm-9:00 am. Using glucose profiles, we determined the mean glucose concentrations (1- and 12-hr intervals), and times spent in hyperglycemia >200 mg/dl or hypoglycemia <60 mg/dl. None of the parameters differed significantly between day-time and night-time in dogs treated with NPH insulin or insulin detemir. In conclusion, this study confirmed, using CGMS, that there are no differences in glucose fluctuations between day- and night-time, in diabetic dogs on a similar feeding regimen and insulin administration.

Topics: Animals; Blood Glucose; Circadian Rhythm; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Dog Diseases; Dogs; Female; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Monitoring, Physiologic; Time Factors

To compare glycaemic control and pregnancy outcome in women with type 1 diabetes treated with the long-acting insulin analogues detemir or glargine.. Retrospective study of singleton pregnancies from 2007 to 2011 in women with type 1 diabetes with a single living fetus at 22 weeks using either insulin detemir (n = 67) or glargine (n = 46) from conception.. Baseline characteristics were similar in the detemir and glargine groups. Haemoglobin A1c was comparable at 8 weeks (median 6.6% (range 5.6-9.8) vs. 6.8% (5.4-10.1), p = 0.15) and at 33 weeks (6.1% (5.1-7.6) vs. 6.2% (4.8-7.2), p = 0.38). The incidence of severe hypoglycaemia was comparable (15 (23%) vs. 10 (23%), p = 0.98). Pre-eclampsia occurred in 9 (14%) vs. 8 (18%), p = 0.52, pre-term delivery in 21 (31%) vs. 16 (35%), (p = 0.70) and 33 (49%) vs. 14 (30%) infants were large for gestational age (p = 0.046). No perinatal deaths were observed. One offspring in each group was born with a major congenital malformation.. Glycaemic control and pregnancy outcome were comparable in women using insulin detemir or glargine, except for a lower prevalence of large for gestational age infants in women on glargine. The use of both long-acting insulin analogues during pregnancy seems safe.

Topics: Adolescent; Adult; Blood Glucose; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Pregnancy; Pregnancy in Diabetics; Pregnancy Outcome; Retrospective Studies; Young Adult

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

Topics: Adult; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Infant, Newborn; Insulin Detemir; Insulin, Long-Acting; Medical Audit; Pregnancy; Pregnancy in Diabetics; Pregnancy Outcome; Retrospective Studies

This study aimed to compare glycemic variations seen among Japanese patients with type 1 diabetes treated with insulin glargine versus insulin detemir using continuous glucose monitoring (CGM) in a crossover design.. Twenty-three patients with type 1 diabetes were enrolled in this study. The subjects were on either insulin glargine followed by insulin detemir twice daily, or vice versa, with no change in the timing of injections. The glycemic variations during 4-day hospitalizations were monitored by CGM while the patients were on either regimen, with a second hospitalization scheduled more than 1 month after the change of the long-acting insulin analogs. CGM data obtained on Day 3 of both hospitalizations were compared.. The subjects had a median age of 44.0 years, a median body mass index of 22.2 kg/m(2), and a median glycosylated hemoglobin of 7.3%. There was no significant difference between the two treatments with a mean glucose level of 156 mg/dL with the insulin glargine treatment versus 150 mg/dL with the insulin detemir treatment; their SD values were 60 versus 51 mg/dL, their mean amplitude of glycemic excursions values were 121 versus 105 mg/dL, and their mean of daily differences values were 45.7 versus 41.4 mg/dL, respectively. In addition, the insulin detemir treatment was associated with a narrower range of postprandial glucose increases after lunch (80 vs. 59 mg/dL; P=0.007).. A comparison of the long-acting insulin analogs administered twice daily in type 1 diabetes demonstrated that insulin detemir may potentially offer better glycemic control after lunch than insulin glargine.

Topics: Adult; Asian People; Blood Glucose; Body Weight; Cross-Over Studies; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Treatment Outcome

Early morning hyperglycemia is frequent among children and adolescents with type 1 diabetes. Reasons are a dawn phenomenon, a Somogyi phenomenon or a lack of insulin in the morning hours. Only few studies are published regarding incidence and relation to different modes of basal insulin treatment in this population.We analyzed all cases recorded in the DPV register from 1995 to 2010. 5 839 patients from 128 centers with at least 3 blood glucose measurements during the last night of a hospital stay were included.24.2% of patients showed a morning hyperglycemia above 200 mg/dl. 8.6% showed a dawn phenomenon, 7.0 % a lack of insulin and 2.0% a Somogyi phenomenon. A dawn phenomenon was significantly less frequent in patients treated with an insulin pump (1.1%) compared to long acting insulin analogs Glargin and Levemir (5.4%) or NPH insulin (8.2%). Lack of insulin was again less frequent during insulin pump treatment compared to other treatments (1.9% vs. 4.9% vs. 5.3%). Median rise of blood glucose levels was 33.4 mg/dl between midnight and 6 a.m. Mode of basal insulin treatment is an important factor: while treatment with an insulin pump led to a blood glucose fall of 28.5 mg/dl between 3 and 6 a.m., treatment with insulin analog or NPH insulin resulted in a rise of 28.5 or 35.9 mg/dl, respectively.This study shows that insulin pump treatment reduces the frequency of morning hyperglycemia caused by the dawn phenomenon or a lack of insulin.

Topics: Blood Glucose; Child; Circadian Rhythm; Diabetes Mellitus, Type 1; Humans; Hyperglycemia; Insulin; Insulin Detemir; Insulin Glargine; Insulin Infusion Systems; Insulin, Isophane; Insulin, Long-Acting; Quality Assurance, Health Care; Registries

Topics: Diabetes Mellitus, Type 1; Female; Humans; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Pregnancy; Pregnancy in Diabetics

Lipoatrophy is a rare complication of treatment with insulin analogues. It has been reported with insulin Lispro (Eli Lilly, Indianapolis, Indiana, USA) and insulin Glargine (Sanofi-Aventis, Paris, France). To our knowledge, this is one of the first reports of lipoatrophy with Aspart, biphasic Aspart and Detemir insulin analogues (Novo Nordisk, Bagsvaerd, Denmark). We report the cases of four children with type I diabetes who were commenced on NovoMix 30 or NovoRapid/Levemir insulin injections. They developed lipoatrophy at the injection sites after 2-3 years of treatment. In two of our patients, lipoatrophy resolved when the injection sites were changed, suggesting that local factors could be the cause of lipoatrophy. However, lipoatrophy developed at the new sites in the other two patients, requiring a change of insulin preparation. Regular examination of the injection sites facilitated early detection of lipoatrophy in our patients. Lipoatrophy completely resolved over 1-2 years in all patients with no recurrence after 3-4 years of follow-up.

Topics: Adolescent; Biphasic Insulins; Child; Child, Preschool; Diabetes Mellitus, Lipoatrophic; Diabetes Mellitus, Type 1; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Lipodystrophy

To evaluate the long-term clinical and economic outcomes associated with insulin detemir and neutral protamine hagedorn (NPH) insulin in combination with mealtime insulin aspart in patients with type 1 diabetes in Sweden, based on data from a two-year, multi-national, open-label, randomized, controlled trial.. Insulin detemir was associated with significant improvements in glycaemic control after 24 months (HbA1c 7.36% versus 7.58%, mean difference -0.22%, p = 0.022) and major hypoglycaemic events (69% risk reduction, p = 0.001) versus NPH. Patients treated with detemir gained less weight (1.7 versus 2.7 kg, P = 0.024). Based on these findings, a published and validated computer model (IMS CORE Diabetes Model) was used to estimate life-expectancy, quality-adjusted life expectancy and both direct medical costs and indirect costs.. Basal-bolus therapy with insulin detemir was projected to improve life expectancy by 0.14 years (15.02 ± 0.19 versus 14.88 ± 0.18 years) and quality-adjusted life expectancy by 0.53 quality-adjusted life years (QALYs) versus NPH (8.35 ± 0.11 versus 7.82 ± 0.10 QALYs). Improvements in QALYs were driven by avoided or delayed diabetes-related complications and fewer hypoglycaemic events. Direct medical costs over patient lifetimes were SEK 26,144 higher in the insulin detemir arm (SEK 995,025 ± 19,580 versus 968,881 ± 19,769), leading to an incremental cost-effectiveness ratio of SEK 49,757 per QALY gained. Capturing indirect costs led to insulin detemir being cost saving over patient lifetimes, by SEK 80,113, compared to NPH (SEK 2,959,909 ± 64,727 versus 3,040,022 ± 62,317).. Compared with NPH, insulin detemir is likely to be cost-effective from a healthcare payer perspective and dominant from a societal perspective in patients with type 1 diabetes in Sweden.

Topics: Adult; Cohort Studies; Cost of Illness; Cost-Benefit Analysis; Diabetes Complications; Diabetes Mellitus, Type 1; Drug Costs; Female; Health Care Costs; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Outcome Assessment, Health Care; Quality-Adjusted Life Years; Sweden; Time Factors

The effects of insulins detemir (Det) and glargine (Glar) on endogenous glucose production (EGP) and net hepatic glucose output (NHGO) were compared.. Arteriovenous difference and tracer ([3-(3) H]glucose) techniques were employed during a two-step hyperinsulinemic euglycaemic clamp in conscious dogs (6 groups, n = 5-6/group). After equilibration and basal sampling (0-120 min), somatostatin was infused and basal glucagon was replaced intraportally. Det or Glar was infused via portal vein (Po), peripheral vein (IV), or bilateral carotid and vertebral arteries (H) at 0.1 and 0.3 mU/kg/min (low Insulin; Glar vs. Det, respectively, 120-420 min) and 4× the low insulin rate (high insulin; 420-540 min).. NHGO and EGP were suppressed and glucose R(d) and infusion rate were stimulated similarly by Det and Glar at both Low and high insulin with each infusion route. Non-esterified fatty acid (NEFA) concentrations during low insulin were 202 ± 37 versus 323 ± 75 µM in DetPo and GlarPo (p < 0.05) and 125 ± 39 versus 263 ± 48 µM in DetIV and GlarIV, respectively (p < 0.05). In DetH versus GlarH, pAkt/Akt (1.7 ± 0.2 vs. 1.0 ± 0.2) and pSTAT3/STAT3 (1.4 ± 0.2 vs. 1.0 ± 0.1) were significantly increased in the liver but not in the hypothalamus.. Det and Glar have similar net effects on acute regulation of hepatic glucose metabolism in vivo regardless of delivery route. Portal and IV detemir delivery reduces circulating NEFA to a greater extent than glargine, and head detemir infusion enhances molecular signalling in the liver. These findings indicate a need for further examination of Det's central and hepatic effects.

Topics: Animals; Blood Glucose; Central Nervous System; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Dogs; Glucose Clamp Technique; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Liver

Topics: Adult; Diabetes Mellitus, Type 1; Female; Glucocorticoids; Humans; Insulin; Insulin Detemir; Insulin, Long-Acting; Prednisone; Serum Sickness

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

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

OBJECTIVE To investigate if long-acting insulin analogs decrease the risk of diabetic ketoacidosis (DKA) in young individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS Of 48,110 type 1 diabetic patients prospectively studied between 2001 and 2008, the incidence of DKA requiring hospitalization was analyzed in 10,682 individuals aged /=2 years. RESULTS The overall rate of DKA was 5.1 (SE +/- 0.2)/100 patient-years. Patients using insulin glargine or detemir (n = 5,317) had a higher DKA incidence than individuals using NPH insulin (n = 5,365, 6.6 +/- 0.4 vs. 3.6 +/- 0.3, P < 0.001). The risk for DKA remained significantly different after adjustment for age at diabetes onset, diabetes duration, A1C, insulin dose, sex, and migration background (P = 0.015, odds ratio 1.357 [1.062-1.734]). CONCLUSIONS Despite their long-acting pharmacokinetics, the use of insulin glargine or detemir is not associated with a lower incidence of DKA compared with NPH insulin.

Topics: Adolescent; Child; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Humans; Hypoglycemic Agents; Incidence; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Risk Factors

Insulin glargine (Lantus) stimulates growth of MCF-7 cells stronger than human insulin. We investigated if serum from diabetic patients treated with glargine versus human insulin may display a similar effect.. Pairs of serum samples from 31 C-peptide negative type-1 diabetic patients were investigated. In cross-over fashion, 23 patients were treated with glargine plus rapid-acting insulin analogues, and similar doses of human NPH and rapid-acting insulin. For comparison, eight patients were treated with insulin detemir (Levemir) and human NPH. MCF-7 cells were incubated with 10% serum and proliferation was assessed after 72 hours.. Serum containing insulin glargine was 1.11(95% CI 1.05-1.18) fold more mitogenic than human insulin-containing serum (p < 0.005); mitogenicity of serum containing detemir was 0.99(95% CI 0.98-1.02) fold that of human insulin-containing serum.. The serum of diabetic patients was slightly stronger mitogenic when using glargine as compared to human insulin or detemir for treatment.

Topics: Breast Neoplasms; C-Peptide; Cell Line, Tumor; Cells; Chemotactic Factors; Diabetes Mellitus; Diabetes Mellitus, Type 1; Female; Humans; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Pilot Projects; Risk Factors

Topics: Adult; Apgar Score; Cesarean Section; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemic Agents; Infant, Newborn; Insulin; Insulin Detemir; Insulin, Long-Acting; Pregnancy; Pregnancy Complications; Pregnancy Outcome

Topics: Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Eating; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin Infusion Systems; Insulin, Isophane; Insulin, Long-Acting; Patient Education as Topic

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

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

Insulin 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

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

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

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 aim of this analysis was to evaluate the long-term clinical and economic outcomes associated with insulin detemir and neutral protamine Hagedorn (NPH) insulin in combination with mealtime insulin aspart in patients with type 1 diabetes in Belgian, French, German, Italian and Spanish settings.. The published and validated IMS CORE Diabetes Model was used to make long-term projections of life expectancy, quality-adjusted life expectancy and direct medical costs. The analysis was based on patient characteristics and treatment effects from a 2-year randomised controlled trial. Events were projected for a time horizon of 50 years. Potential uncertainty using a modelling approach was addressed.. Basal-bolus therapy with insulin detemir was projected to improve quality-adjusted life expectancy by 0.45 years versus NPH in the German setting, with similar improvements in the other countries. Insulin detemir was associated with cost savings in Belgium, Germany and Spain. In France and Italy, lifetime costs were slightly higher in the detemir arm, leading to incremental cost-effectiveness ratios of 519 euro per QALY gained and 3,256 euro per QALY gained, respectively.. Compared to NPH, insulin detemir is likely to be a dominant treatment strategy in Belgium, Germany and Spain and highly cost-effective in France and Italy in patients with type 1 diabetes.

Topics: Adolescent; Adult; Aged; Cost-Benefit Analysis; Diabetes Mellitus, Type 1; Drug Administration Schedule; Drug Dosage Calculations; Europe; Female; Financing, Personal; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Life Expectancy; Male; Middle Aged; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Sensitivity and Specificity; Young Adult

Subjects with type 1 diabetes mellitus (T1DM) eventually develop insulin resistance and other features of T2DM such as cardiovascular disorders. The exact mechanism has been not been completely understood. In this study, we tested the hypothesis that excessive or inappropriate exposure to insulin is a primary mediator of insulin resistance in T1DM. We found that continuous exposure of mice with non-obese diabetes to insulin detemir, which is similar to some current conventional treatment of human T1DM, induced severe insulin resistance, whereas untreated hyperglycemia for the same amount of time (2 weeks) did not cause obvious insulin resistance. Insulin resistance was accompanied by decreased mitochondrial production as evaluated by mitochondrial DNA and levels of transcripts and proteins of mitochondrion-associated genes, increased ectopic fat accumulation in liver and skeletal muscle (gastrocnemius) evaluated by measurements of triglyceride content, and elevated oxidative stress detected by the GSH/GSSG ratio. Prolonged exposure of cultured hepatocytes to insulin induced significant insulin resistance, whereas the same length of exposure to a high level of glucose (33 mm) did not cause obvious insulin resistance. Furthermore, our results showed that prolonged exposure to insulin caused oxidative stress, and blockade of mitochondrion-derived oxidative stress by overexpression of manganese-superoxide dismutase prevented insulin resistance induced by the prolonged exposure to insulin. Together, our results show that excessive exposure to insulin is a primary inducer of insulin resistance in T1DM in mice.

Topics: Animals; Diabetes Mellitus, Type 1; Glucose; Hepatocytes; Humans; Hyperglycemia; Insulin; Insulin Detemir; Insulin Resistance; Insulin, Long-Acting; Lipid Metabolism; Mice; Mitochondria; Oxidative Stress; Time Factors

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

Topics: Adult; Diabetes Mellitus, Type 1; Female; Fetal Development; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin, Long-Acting; Pregnancy; Pregnancy in Diabetics

To evaluate long-term effects of treatment with insulin analogue glargine in patients with type 1 diabetes mellitus and to follow up their further course of life.. Retrospective evaluation of 114 patients who, from September 2004, had their basal insulin changed from NPH insulin to insulin glargine. Treatment was changed again in patients in whom a year-long treatment with insulin glargine did not bring improvement in diabetes control. The original sample was divided into 3 groups and the results compared. Compensation of diabetes (HbA1c) after 1, 2 and 3 years and changes to basal and bolus daily insulin dose and body weight were evaluated.. The results are presented as median and 25th and 75th percentile. Group A--75 patients (65%) treated for the entire evaluation period with insulin glargine. Initial HbA1c was 7.3 (6.4-8.2)%, 6.9 (6.0-8.4)% after 1 year, 7.1 (5.9-7.9)% after 2 years and 6.6 (5.5-7.7)% after 3 years (p < 0.001). We did not identify any statistically significant changes to total, basal or bolus daily dose of insulin or statistically significant body weight increase over the evaluation period. Group B--19 patients (17%). Switch from insulin glargine to detemir twice daily. Initial HbA1c was 7.3 (6.9-8.5)%, 7.4 (6.8-8.7)% after 1 year of treatment with insulin glargine, 7.7 (7.2-8.1)% before the treatment switch and 7.8 (6.7-8.5)% (NS) after 3 years of treatment. Daily dose of total, basal and bolus insulin did not change and, similarly, no statistically significant change to patients' bodyweight was identified. Group C--17 patients (15%). Switch from insulin glargine to an insulin pump. This group had better initial compensation with HbA1c 6.7(5.7-8.6)%, HbA1c after 1 year was 6.2 (5.6-8.1)%, 7.0 (6.0-7.4)% before the treatment switch and 6.3 (5.2-7.7)% after 3 years of treatment. Total daily insulin dose: 48 (34-60)-38 (25-49) IU/day (NS). Basal daily insulin dose: 17.5 (13-28) IU/day-23 (12-32) IU/day (NS). Bolus daily dose decreased significantly: from 25.5 (21-33) to 15.5 (12-22) IU/day (p < 0.01). Body weight: 76 (71-97) kg-73 (72-99) kg (NS). Only 3% of patients went back to NPH insulin.. Insulin glargine brings improved control of diabetes. The dose of insulin glargine did not differ from NPH insulin. No statistically significant body weight increase was observed during the evaluation period.

Topics: Adult; Body Weight; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged

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

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

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

Paper presents an evaluation of diabetes control after switching from NPH insulin to detemir in children with type 1 diabetes.. We performed a non-randomized, observational, multicentre study on the first group of children whose treatment switched from NPH to insulin detemir in four centers of paediatric diabetes. A total of 72 children (39 boys and 33 girls) were included in the analysis. The average age at intervention was 10.6 +/- 4.7 yrs, the average age at diabetes onset was 6.2 +/- 4.3 yrs. Diabetes control was assessed 3 months prior to the switch and subsequently during 3-month intervals.. Mean HbA(1c) decreased from 6.9% at baseline to 6.4% after 3 months of detemir therapy (p = 0.0003). However, in the next months we observed a trend for increasing the HbA(1c), and no statistically significant difference in HbA(1c) was observed at the 6, 9 and 12 months visits vs. baseline. Fasting glycaemia decreased significantly after 3 months of treatment with detemir in comparison with the baseline (the mean value of the difference was 2.1 mmol/l, CI 95% 1.5-2.6, p = 1.4*10(-10)), and this effect was detectable during all the observational period (month 12 vs. baseline 2.6 mmol/l, p < 10(-8)).. Switching basal insulin from NPH insulin to detemir resulted in a short-term improvement of HbA(1c), and a long-term decreasing of fasting glycaemia.

Topics: Adolescent; Blood Glucose; Child; Child, Preschool; Diabetes Mellitus, Type 1; Fasting; Female; Glycated Hemoglobin; Humans; Infant; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male

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

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

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

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

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

Lipoatrophy is a rare cutaneous side-effect that can develop at the site of insulin injection. Since the introduction of human recombinant insulin the number of cases has decreased although cases have been reported in association with the use of rapid acting insulin analogues and continuous subcutaneous insulin infusion (CSII), recently one case has been reported with the use of insulin glargine. Insulin-induced lipoatrophy is a subcutaneous fat atrophy at the sites of injection which is relevant not only because of the cosmetic problem, but also because of the variability of absorption it causes in the site of injection. This report describes a patient with a type 1 diabetes mellitus who develops a lipoatrophy induced by insulin detemir. To our understanding this is one of the first reported cases of lipoatrophy induced by insulin detemir.

Topics: Adipose Tissue; Adult; Atrophy; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Detemir; Insulin, Long-Acting; Lipodystrophy

Topics: Area Under Curve; Cross-Over Studies; Diabetes Mellitus, Type 1; Double-Blind Method; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Randomized Controlled Trials as Topic

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

Diabetes is a major challenge to the Danish health care system, and complications account for the majority of total treatment costs.. The majority of type 1 diabetes patients in Denmark are treated with the flexible basal-bolus insulin regimen. Use of insulin analogues provides superior metabolic control, lower blood glucose viability, flexible life style, reduced frequency of hypoglycaemia and no undesired weight gain. The long term health economic consequences were projected in a published and validated Markov model. Treatment effects of insulin analogues and a similar human insulin regimen were based on results from a clinical RCT study and Danish health care costs were applied in the model.. In the model, the improved glycaemic control and the reduction in hypoglycaemia episodes obtained with insulin analogues resulted in a reduction in late stage diabetes complications, improved quality of life and increased life expectancy compared to human insulin. The incremental costs-effectiveness ratio was estimated to DKK 55,867 per quality-adjusted life year gained, which is considered beneficial to society.. Modelling predicts insulin analogues to be a cost-effective alternative to human insulin in Denmark.

Topics: Adult; Cost-Benefit Analysis; Denmark; Diabetes Mellitus, Type 1; Drug Costs; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin, Long-Acting; Life Expectancy; Life Style; Male; Markov Chains; Middle Aged; Quality-Adjusted Life Years

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

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 analyse current therapeutic strategies for prandial insulin substitution in a large number of children and adolescents with Type 1 diabetes in Germany and Austria, along with changes in therapeutic habits and outcome.. We classified the data of 26 687 patients, treated from 1995 to 2005 in 152 paediatric clinics, using a database established for quality control and scientific surveys in paediatric diabetology (DPV).. Seventy-three per cent of all patients (mean age 13.6 years., mean duration of diabetes 5.4 years.) were treated with > or = 4 daily injections (intensified conventional treatment; ICT), 14% with continuous subcutaneous insulin infusion (CSII), 13% with 1-3 injections per day (conventional treatment). Frequency of daily injections increased with age, duration of diabetes and insulin dose. The insulin dose at breakfast was higher than for the evening meal or lunch, from diagnosis onwards. Individuals using insulin analogues received up to 11% higher insulin doses per day compared with patients treated with human insulin. The time of day, age, duration of diabetes, female gender, insulin analogues and ICT all had a significant influence on prandial insulin doses. Although the number of patients treated with ICT or CSII increased over the period of observation, mean glycated haemoglobin (HbA(1c)) was approximately 8.0% each year, and decreased by only 0.01%.. Eighty-seven per cent of patients were treated with ICT or CSII. However, while this percentage increased over the observation period, mean HbA(1c) was almost constant. Longer duration of diabetes, increasing age, female gender, insulin analogues and ICT were associated with higher prandial insulin doses.

Topics: Adolescent; Adult; Austria; Blood Glucose; Child; Child, Preschool; Cohort Studies; Diabetes Mellitus, Type 1; Drug Administration Schedule; Germany; Humans; Hypoglycemic Agents; Infant; Insulin; Insulin Detemir; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Male

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

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

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

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

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

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

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

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Injections, Subcutaneous; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Male; Randomized Controlled Trials as Topic; Risk Assessment; Severity of Illness Index; Treatment Outcome

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