exenatide 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

The objective in developing a new type 2 diabetes therapy is to achieve greater safety and better efficacy. Newly registered drugs include lixisenatide, QW exenatide, dapagliflozin and insulin degludec. Once weekly gliptins and other substances are under development.

Topics: Benzhydryl Compounds; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Administration Schedule; Exenatide; Glucosides; Humans; Hypoglycemic Agents; Insulin, Long-Acting; Peptides; Venoms

Type 2 diabetes mellitus (T2DM) is a global public health problem. Due to the progressive nature of the disease, a combination(s) of two or more drugs acting on different pathophysiological process is often necessary to achieve early and sustained achievement of individualized glycemic targets. At the same time, choosing the safest option to avoid hypoglycemia is of paramount importance. GLP-1 analogues are a relatively recent class of anti-diabetic drugs, and are highly effective with an acceptable safety profile. Attempts have been made to combine GLP-1 analogues with basal insulin for management of T2DM. Presently GLP-1 analogues like exenatide/long acting exenatide and liraglutide have been co-administered with basal insulin like glargine and detemir respectively, and are approved by regulatory agencies. Currently a fixed dose combination (FDC) of insulin degludec and liraglutide is under development. GLP-1 analogue and insulin as FDC or by co-administration, is a rational method of controlling fasting and postprandial glucose effectively. The efficacy and safety of this combination has been studied in a wide population with promising outcomes. Innovative use of GLP-1 analogues beyond diabetes is also being attempted, and a variety of patents are filed or granted for the same. This review summarizes the current status of GLP-1 and insulin combination in the management of T2DM and highlights the new frontiers in research involving GLP-1. Patents on combination of GLP-1 and insulin which were granted earlier, and the ones which have been applied for, are also discussed.

Topics: Diabetes Mellitus, Type 2; Drug Combinations; Drug Therapy, Combination; Exenatide; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Insulin, Long-Acting; Liraglutide; Peptides; Venoms