Glucagon-like peptide analogues for type 2 diabetes mellitus: systematic review and meta-analysis

Abstract

BackgroundGlucagon-like peptide (GLP-1) analogues are a new class of drugs used in the treatment of type 2 diabetes. They are given by injection, and regulate glucose levels by stimulating glucose-dependent insulin secretion and biosynthesis, suppressing glucagon secretion, and delaying gastric emptying and promoting satiety. This systematic review aims to provide evidence on the clinical effectiveness of the GLP-1 agonists in patients not achieving satisfactory glycaemic control with one or more oral glucose lowering drugs.MethodsMEDLINE, EMBASE, the Cochrane Library and Web of Science were searched to find the relevant papers. We identified 28 randomised controlled trials comparing GLP-1 analogues with placebo, other glucose-lowering agents, or another GLP-1 analogue, in patients with type 2 diabetes with inadequate control on a single oral agent, or on dual therapy. Primary outcomes included HbA1c, weight change and adverse events.ResultsStudies were mostly of short duration, usually 26 weeks. All GLP-1 agonists reduced HbA1c by about 1% compared to placebo. Exenatide twice daily and insulin gave similar reductions in HbA1c, but exenatide 2 mg once weekly and liraglutide 1.8 mg daily reduced it by 0.20% and 0.30% respectively more than glargine. Liraglutide 1.2 mg daily reduced HbA1c by 0.34% more than sitagliptin 100 mg daily. Exenatide and liraglutide gave similar improvements in HbA1c to sulphonylureas. Exenatide 2 mg weekly and liraglutide 1.8 mg daily reduced HbA1c by more than exenatide 10 μg twice daily and sitagliptin 100 mg daily. Exenatide 2 mg weekly reduced HbA1c by 0.3% more than pioglitazone 45 mg daily.Exenatide and liraglutide resulted in greater weight loss (from 2.3 to 5.5 kg) than active comparators. This was not due simply to nausea. Hypoglycaemia was uncommon, except when combined with a sulphonylurea. The commonest adverse events with all GLP-1 agonists were initial nausea and vomiting. The GLP-1 agonists have some effect on beta-cell function, but this is not sustained after the drug is stopped.ConclusionsGLP-1 agonists are effective in improving glycaemic control and promoting weight loss.

Gastrointestinal Adverse Events of Glucagon-Like Peptide-1 Receptor Agonists in Patients with Type 2 Diabetes: A Systematic Review and Network Meta-Analysis

“…Our results were similar to previous studies, which reported that GLP-1 RAs have a significant effect on GI AEs compared with other treatments for patients with T2DM. 11,[29][30][31] Two double-blind placebo-controlled studies showed the highest dose of TAS (20 mg once weekly) was associated with higher incidences of nausea (52% and 31%) and vomiting (22% and 17.8%) than placebo. 32,33 Dose-response studies showed a dosedependent increase of nausea from EX5BID (range, 3-39%) to EX10 BID (range, 13-51%) and an increase of GI AEs from LIR0.6QD to LIR1.2QD to LIR1.8QD.…”

Incretin based drugs and the risk of pancreatic cancer: international multicentre cohort study

“…2 3 This concern has been heightened by an analysis of the US Food and Drug Administration adverse events database, where the spontaneous reporting rate of pancreatic cancer was 2.9 and 2.7 times higher with exenatide and sitagliptin, respectively, compared with other oral antidiabetic drugs. 4 In contrast, randomised controlled trials have not demonstrated this signal, [5][6][7][8][9][10][11] although most of these trials were of short duration and none were designed or powered to assess the risk of pancreatic cancer.…”

Treatment with GLP1 receptor agonists reduce serum CRP concentrations in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials

“…Glucagon-like peptide-1 (GLP-1) is a gut hormone, secreted from the intestine in response to meal ingestion, which stimulates insulin secretion and inhibits glucagon release in a dose-dependent fashion [3]. GLP-1 can suppress appetite, food intake, decelerate gastric emptying and induce satiety, so it plays an important role in the regulation of blood glucose [4,5]. GLP-1 receptor agonists (GLP-1 RAs) include exenatide, liraglutide, albiglutide, taspoglutide, lixisenatide.…”