insulin-degludec and Weight-Gain

We aimed to assess the comparative efficacy and safety of second-generation basal insulins (glargine U300 and degludec U100) vs. neutral protamine Hagedorn (NPH) and first-generation basal insulins (glargine U100 and detemir) in type 1 diabetes (T1D) adults.PubMed, the Cochrane Library, ClinicalTrials.gov, and Google Scholar (until January 2021) were systematically searched. Randomized controlled trials (RCTs) with ≥ 12 weeks of follow-up comparing efficacy (HbA

Topics: Adult; Diabetes Mellitus, Type 1; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Network Meta-Analysis; Randomized Controlled Trials as Topic; Treatment Outcome; Weight Gain

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

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

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

Type 2 diabetes is a complex disease requiring individualized and often multi-faceted treatment plans. Balancing glycemic control with adverse medication side effects can be challenging. Combination therapy of basal insulin and GLP-1 receptor agonist therapy appears to provide a balance between glycemic efficacy, hypoglycemia and weight gain.. Available pharmacokinetic data, clinical trials and abstracts regarding fixed-ratio combination of insulin degludec and liraglutide were reviewed. Literature was searched from PubMed and available abstracts using the search term IDegLira up to June 2016.. Fixed-ratio combination of insulin degludec and liraglutide is associated with sustained glucose-lowering effects as assessed by HbA1c reduction. Overall, hypoglycemia is reduced and weight loss is observed compared to basal insulin alone. There is no significant increase in gastrointestinal side-effects, including nausea compared to non-glucagon-like peptide-1 receptor agonists. Pen injector delivery and dose-step titration allow for individualized therapy intensification. Combined treatment for type 2 diabetes with degludec and liraglutide therapy provides complementary therapeutic efficacy in the treatment of individuals with type 2 diabetes.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Combinations; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin, Long-Acting; Liraglutide; Weight Gain

The treatment of patients with type 2 diabetes mellitus remains challenging, as it goes beyond adequate glycemic control, in particular addressing weight, blood pressure and other contributors to cardiovascular disease. In addition, the progressive nature of type 2 diabetes mellitus demands the intensification and combination of glucose lowering therapies. In many patients, there is a clinical inertia for the initiation of insulin therapy, leading to failure in reaching glycemic targets in many patients.. Recently a fixed-ratio combination therapy of the basal insulin degludec and the glucagon-like peptide-1 analogue liraglutide has been developed and approved by the EMA. The rationale for this combination, as well as an overview of the published phase III clinical trials (DUAL I,II,V), are covered, highlighting the most important conclusions.. The combination therapy of insulin degludec and liraglutide is an attractive therapeutic strategy in patients with type 2 diabetes mellitus as it gives a robust glycemic control with a low risk for hypoglycemia and less weight gain or even weight loss. The fixed-ratio combination of insulin degludec and liraglutide offers a smart therapeutic strategy in patients with type 2 diabetes mellitus where basal insulin needs to be initiated or intensified.

Topics: Animals; Blood Glucose; Blood Pressure; Body Weight; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Drug Combinations; Glucagon-Like Peptide 1; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin, Long-Acting; Liraglutide; Weight Gain

The limitations of current basal insulin preparations include concerns related to their pharmacokinetic and pharmacodynamic properties, hypoglycaemia, weight gain, and perception of management complexity, including rigid dosing schedules. Insulin degludec (IDeg) is a novel basal insulin with improved pharmacokinetic and pharmacodynamic properties compared to insulin glargine (IGlar) including a long half-life of ∼25 h and a duration of action >42 h at steady state, providing a flat and stable blood glucose-lowering effect when injected once daily. Evidence from phase 3a clinical trials with a treat-to-target design in patients with type 1 and type 2 diabetes has shown that IDeg has similar efficacy to IGlar, with a 9% and 26% reduction in risk of overall and nocturnal hypoglycaemia, respectively (in the pooled population) during the entire treatment period, and a 16% and 32% reduction during the maintenance period, respectively. Given its pharmacodynamic properties, IDeg offers a broad dosing window, allowing for flexible dose administration, if required. Two different formulations of IDeg are available (100 units/mL [U100] and 200 units/mL), the latter providing the same IDeg dose as the U100 formulation in half the injection volume. The unique pharmacokinetic profile of IDeg facilitates glycaemic control while minimising the risk of nocturnal hypoglycaemia.

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Administration Schedule; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Long-Acting; Weight Gain

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

To review the pharmacology, pharmacokinetics, clinical trial data, adverse effects, and potential role in therapy of insulin degludec.. Articles were identified using the MEDLINE database (January 1996-December 2012). Abstracts and posters were identified from respective congressional websites and published supplements of the American Diabetes Association, the European Association for the Study of Diabetes, and the American Association of Clinical Endocrinologists (January 2008-December 2012). Clinicaltrials.gov was used to identify any ongoing clinical trials or completed trials whose results had not been presented or published.. All available studies were reviewed for inclusion; pharmacokinetic studies were limited to those reporting human data.. Insulin degludec is a novel, ultra-long-acting basal insulin analogue that has a similar safety and efficacy profile when compared with insulin glargine in patients with type 1 or type 2 diabetes. Clinical trials have indicated that there is less hypoglycemia, particularly nocturnal hypoglycemia, associated with this agent.. If insulin degludec is approved, it may offer an alternative basal insulin for patients needing more flexible dosing, having a history of nocturnal hypoglycemia, or those with severe insulin resistance needing a higher concentration of basal insulin.

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Combinations; Drugs, Investigational; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Resistance; Insulin, Long-Acting; United States; Weight Gain

In participants with type 2 diabetes (T2D) and HbA1c >9.0-10.0%, guidelines recommend treatment with basal-bolus insulin.. This randomized trial compared the efficacy and safety of insulin degludec and liraglutide (IDegLira) and basal-bolus among participants with high HbA1c ≥9.0-15.0%, previously treated with 2 or 3 oral agents and/or basal insulin, allocated (1:1) to basal-bolus (n = 73) or IDegLira (n = 72). The primary end point was noninferiority (0.4%) in HbA1c reduction between groups.. Among 145 participants (HbA1c 10.8% ± 1.3), there was no statistically significant difference in HbA1c reduction (3.18% ± 2.29 vs. 3.00% ± 1.79, P = 0.65; estimated treatment difference (ETD) 0.18%, 95% CI -0.59, 0.94) between the IDegLira and basal-bolus groups. IDegLira resulted in significantly lower rates of hypoglycemia <70 mg/dL (26% vs. 48%, P = 0.008; odds ratio 0.39, 95% CI 0.19, 0.78), and less weight gain (1.24 ± 8.33 vs. 5.84 ± 6.18 kg, P = 0.001; ETD -4.60, 95% CI -7.33, -1.87).. In participants with T2D and HbA1c ≥9.0-15.0%, IDegLira resulted in similar HbA1c reduction, less hypoglycemia, and less weight gain compared with the basal-bolus regimen.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Drug Combinations; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin, Long-Acting; Liraglutide; Weight Gain

Topics: Anti-Obesity Agents; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Drug Combinations; Drug Monitoring; Drug Resistance, Multiple; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incretins; Insulin Glargine; Insulin, Long-Acting; Liraglutide; Metformin; Obesity; Overweight; Weight Gain; Weight Loss

IDegLira, a fixed ratio combination of insulin degludec and glucagon-like peptide-1 receptor agonist liraglutide, utilizes the complementary mechanisms of action of these two agents to improve glycemic control with low risk of hypoglycemia and avoidance of weight gain. The aim of the present analysis was to assess the long-term cost-effectiveness of IDegLira vs liraglutide added to basal insulin, for patients with type 2 diabetes not achieving glycemic control on basal insulin in the US setting.. Projections of lifetime costs and clinical outcomes were made using the IMS CORE Diabetes Model. Treatment effect data for patients receiving IDegLira and liraglutide added to basal insulin were modeled based on the outcomes of a published indirect comparison, as no head-to-head clinical trial data is currently available. Costs were accounted in 2015 US dollars ($) from a healthcare payer perspective.. IDegLira was associated with small improvements in quality-adjusted life expectancy compared with liraglutide added to basal insulin (8.94 vs 8.91 discounted quality-adjusted life years [QALYs]). The key driver of improved clinical outcomes was the greater reduction in glycated hemoglobin associated with IDegLira. IDegLira was associated with mean costs savings of $17,687 over patient lifetimes vs liraglutide added to basal insulin, resulting from lower treatment costs and cost savings as a result of complications avoided.. The present long-term modeling analysis found that IDegLira was dominant vs liraglutide added to basal insulin for patients with type 2 diabetes failing to achieve glycemic control on basal insulin in the US, improving clinical outcomes and reducing direct costs.

Topics: Blood Glucose; Blood Pressure; Body Mass Index; Cost-Benefit Analysis; Diabetes Complications; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin, Long-Acting; Lipids; Liraglutide; Markov Chains; Models, Economic; Monte Carlo Method; Quality-Adjusted Life Years; United States; Weight Gain

Achieving glycemic control remains a challenge for patients with type 2 diabetes, even with insulin therapy.. To assess whether a fixed ratio of insulin degludec/liraglutide was noninferior to continued titration of insulin glargine in patients with uncontrolled type 2 diabetes treated with insulin glargine and metformin.. Phase 3, multinational, multicenter, 26-week, randomized, open-label, 2-group, treat-to-target trial conducted at 75 centers in 10 countries from September 2013 to November 2014 among 557 patients with uncontrolled diabetes treated with glargine (20-50 U) and metformin (≥1500 mg/d) with glycated hemoglobin (HbA1c) levels of 7% to 10% and a body mass index of 40 or lower.. 1:1 randomization to degludec/liraglutide (n = 278; maximum dose, 50 U of degludec/1.8 mg of liraglutide) or glargine (n = 279; no maximum dose), with twice-weekly titration to a glucose target of 72 to 90 mg/dL.. Primary outcome measure was change in HbA1c level after 26 weeks, with a noninferiority margin of 0.3% (upper bound of 95% CI, <0.3%). If noninferiority of degludec/liraglutide was achieved, secondary end points were tested for statistical superiority and included change in HbA1c level, change in body weight, and rate of confirmed hypoglycemic episodes.. Among 557 randomized patients (mean: age, 58.8 years; women, 49.7%), 92.5% of patients completed the trial and provided data at 26 weeks. Baseline HbA1c level was 8.4% for the degludec/liraglutide group and 8.2% for the glargine group. HbA1c level reduction was greater with degludec/liraglutide vs glargine (-1.81% for the degludec/liraglutide group vs -1.13% for the glargine group; estimated treatment difference [ETD], -0.59% [95% CI, -0.74% to -0.45%]), meeting criteria for noninferiority (P < .001), and also meeting criteria for statistical superiority (P < .001). Treatment with degludec/liraglutide was also associated with weight loss compared with weight gain with glargine (-1.4 kg for degludec/liraglutide vs 1.8 kg for glargine; ETD, -3.20 kg [95% CI, -3.77 to -2.64],P < .001) and fewer confirmed hypoglycemic episodes (episodes/patient-year exposure, 2.23 for degludec/liraglutide vs 5.05 for glargine; estimated rate ratio, 0.43 [95% CI, 0.30 to 0.61],P < .001). Overall and serious adverse event rates were similar in the 2 groups, except for more nonserious gastrointestinal adverse events reported with degludec/liraglutide (adverse events, 79 for degludec/liraglutide vs 18 for glargine).. Among patients with uncontrolled type 2 diabetes taking glargine and metformin, treatment with degludec/liraglutide compared with up-titration of glargine resulted in noninferior HbA1c levels, with secondary analyses indicating greater HbA1c level reduction after 26 weeks of treatment. Further studies are needed to assess longer-term efficacy and safety.. clinicaltrials.gov Identifier: NCT01952145.

Topics: Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Metformin; Middle Aged; Weight Gain; Weight Loss

The time-course when changes in glycemic control and body weight were first manifest in patients with type 2 diabetes mellitus (T2DM) treated with a combination of insulin degludec and liraglutide (IDegLira) was assessed, comparing IDegLira to its individual components.. Data from weeks 0-12 from two studies were analyzed, one comparing IDegLira to each component (DUAL I), and one comparing IDegLira to insulin degludec titrated to a maximum 50 units (DUAL II). Efficacy endpoints included glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) reduction, proportion of patients achieving HbA1c [<7.0 % (<53.0 mmol/mol)] and FPG (≤7.2 mmol/L) targets, and proportion achieving HbA1c target without hypoglycemia and without hypoglycemia and weight gain.. Mean HbA1c was lower, and the proportion of patients reaching target HbA1c greater, with IDegLira versus comparators (both studies) at weeks 8 and 12. Proportions of patients reaching target HbA1c without hypoglycemia and without hypoglycemia and weight gain were higher for IDegLira versus insulin degludec, though not versus liraglutide. Mean FPG was lower with IDegLira, and the proportion achieving target FPG higher, versus components (both studies) from weeks 4-12. IDegLira was associated with mean weight reduction from weeks 4-12, although less than with liraglutide alone. Hypoglycemia occurred infrequently in weeks 0-12, with no difference in incidence between IDegLira and insulin degludec in either study.. IDegLira reduces plasma glucose to a greater extent than its components, measurable within the first 12 weeks of therapy, and without weight gain or an increased hypoglycemia risk versus insulin degludec.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Drug Combinations; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin, Long-Acting; Liraglutide; Male; Middle Aged; Weight Gain; Weight Loss

Due to the progressive nature of type 2 diabetes (T2D), the majority of patients require increasing levels of therapy to achieve and maintain good glycemic control. At present, once patients become uncontrolled on oral antidiabetic therapies, the two primary treatment options are glucagon-like peptide-1 receptor agonists (GLP-1RAs) or basal insulin, although earlier use of GLP-1RAs has also been advocated. While both of these drug classes have proven efficacy in treating T2D, there can be limitations to their use in some patients, and resistance to further treatment intensification among both patients and physicians. More recently, treatment incorporating both a GLP-1RA and a basal insulin has been used successfully in the clinic and the first such combination product, IDegLira (insulin degludec+liraglutide), has recently been approved for use in Europe. IDegLira combines insulin degludec and the GLP-1RA liraglutide in a single injection. In both insulin-naïve and basal insulin-treated individuals with T2D, IDegLira has demonstrated greater reductions in glycated hemoglobin (HbA1c) than either of the individual components, with a low rate of hypoglycemia and weight loss. IDegLira may provide a new option for patients requiring treatment intensification but for whom increased weight or a higher risk of hypoglycemia are barriers. This article discusses the rationale behind combining these two drug classes and reviews the available clinical evidence for the efficacy and safety of IDegLira.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Drug Combinations; Europe; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin; Insulin, Long-Acting; Liraglutide; Treatment Outcome; Weight Gain