incretins and insulin-degludec

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

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

In type 2 diabetes (T2D), treatment is optimised to minimise hyperglycaemia and the risk of microvascular complications. While there are a number of effective treatments, intensive treatment is associated with negative side effects such as increased hypoglycaemia and weight gain. With complementary modes of action, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and a basal insulin in combination offer an alternative to basal-bolus therapy in T2D. This review describes the rationale behind this treatment combination and presents clinical data available for IDegLira, the first basal insulin (insulin degludec) and GLP-1RA (liraglutide) co-formulation available in one pen for a single injection daily.

Topics: Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Drug Combinations; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Incretins; Injections; Insulin Resistance; Insulin, Long-Acting; Liraglutide; Treatment Outcome

Suboptimal blood glucose control among patients with type 2 diabetes continues to support the need for new pharmacologic approaches.. The purpose of this commentary was to highlight newly available and soon-to-be available agents that are promising tools for targeting specific pathophysiologic pathways in the management of diabetes.. Published evidence to support the application of novel incretin-based therapies, dipeptidyl peptidase (DPP)-4 inhibitors, sodium-glucose cotransporter (SGLT)-2 inhibitors, other oral agents and insulins for managing specific aspects of type 2 diabetes, as well as disadvantages associated with those novel medications, are discussed.. Several new glucagon-like peptide (GLP)-1 receptor agonists with different time frames of action, although each has unique advantages and disadvantages, have been through clinical trials. Examples of these are lixisenatide and albiglutide. Currently available DPP-4 inhibitor agents, important for inhibiting the breakdown of endogenous GLP-1, have not been associated with weight gain or hypoglycemia. SGLT-2 inhibitors, which do not depend on insulin secretion or insulin action, may be advantageous in that they appear to be broadly efficacious at all stages of diabetes. New insulin analogues, such as degludec and U-500, improve glycemic control without contributing to hypoglycemia.. Advances in pharmacologic options offer the promise of improving glycemic control for longer periods, with limited glycemic fluctuations, hypoglycemia, and weight gain. However, the effectiveness of these agents ultimately depends on their availability to providers managing the health care of patients at high risk for poor diabetes outcomes and patients' use of them as directed. Long-term effectiveness and safety trials are ongoing.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Female; Glucagon-Like Peptide 1; Humans; Hypoglycemia; Hypoglycemic Agents; Incretins; Insulin; Insulin, Long-Acting; Male; Peptides

The central role of insulin in the management of patients with type 1 diabetes mellitus (T1DM) remains, nearly a century after its first use in humans. In patients with type 2 diabetes mellitus (T2DM), the role of insulin has evolved as other therapies have been introduced, with insulin now used across the spectrum of the disease. This article discusses the use of insulin in patients with T1DM or T2DM, including combined use with other agents in T2DM, with an emphasis on incretin-based therapies. In addition, new insulin products and concentrations are discussed along with their varied routes of administration.

Topics: Chemistry, Pharmaceutical; Diabetes Mellitus; Drug Combinations; Humans; Hypoglycemic Agents; Incretins; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Insulins; Treatment Outcome

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

Topics: Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Drug Combinations; Humans; Hypoglycemic Agents; Incretins; Insulin, Long-Acting; Liraglutide; Treatment Outcome