Effects of Glucagon-Like Peptide-1 Receptor Agonists on Weight Loss in Patients with Type 2 Diabetes: A Systematic Review and Network Meta-Analysis

Abstract

To evaluate the effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on weight reduction in patients with Type 2 diabetes mellitus (Type 2 DM), a network meta-analysis was conducted. MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov were searched from 1950 to October 2013. Randomized controlled trials (RCTs) involving GLP-1 RAs were included if they provided information on body weight. A total of 51 RCTs were included and 17521 participants were enrolled. The mean duration of 51 RCTs was 31 weeks. Exenatide 10 μg twice daily (EX10BID) reduced weight compared with exenatide 5 μg twice daily (EX5BID), liraglutide 0.6 mg once daily (LIR0.6QD), liraglutide—1.2 mg once daily (LIR1.2QD), and placebo treatment, with mean differences of −1.07 kg (95% CI: −2.41, −0.02), −2.38 kg (95% CI: −3.71, −1.06), −1.62 kg (95% CI: −2.79, −0.43), and −1.92 kg (95% CI: −2.61, −1.24), respectively. Reductions of weight treated with liraglutide—1.8 mg once daily (LIR1.8QD) reach statistical significance (−1.43 kg (95% CI: −2.73, −0.15)) versus LIR1.2QD and (−0.98 kg (95% CI: −1.94, −0.02)) versus placebo. Network meta-analysis found that EX10BID, LIR1.8QD, and EX2QW obtained a higher proportion of patients with weight loss than other traditional hypoglycemic agents. Our results suggest GLP-1 RAs are promising candidates for weight control in comparison with traditional hypoglycemic drugs, and EX10BID, LIR1.8QD, and EX2QW rank the top three drugs.

Gut microbiota, obesity and diabetes

“…GLP-1 also acts systemically on the pancreas, liver, heart, stomach and brain, impacting on gastric emptying, satiety and lipid absorption and metabolism 200 201. As such, a plethora of drugs have been developed as GLP-1R agonists or blockers (gliptins) of DPP-4, the enzyme that cleaves active GLP-1 in circulation 202. Although GLP-1-based therapies have been entirely targeted towards the treatment of T2D, it has become clear that this full-length form of the peptide may have significant potential as a T1D therapy.…”

GLP-1 based therapies: clinical implications for gastroenterologists

“…While DPP-4Is are weight-neutral, GLP-1RAs (short-acting and long-acting) induce weight loss in a dose-dependent manner 59. Recently, a high-dose preparation of the long-acting GLP-1RA liraglutide (3.0 mg) has been approved for weight reduction 60.…”

Incretin based treatments and mortality in patients with type 2 diabetes: systematic review and meta-analysis

“…2 Their effects on glucose control are well established, [3][4][5] with additional benefits of weight loss, antihypertensive effects, and minimal risk of hypoglycemia. [4][5][6][7][8][9][10][11] A recent large randomised trial (SAVOR-TIMI 53 study 12 ) including patients with type 2 diabetes with established, or at risk for, cardiovascular disease, however, suggested possible increased mortality with saxagliptin versus placebo (5.1% v 4.6%). In response, the US Food and Drug Administration released the following statement in 2015: "A potential increase in all cause mortality with saxagliptin was observed-The ITT on-study analysis suggested an increase in all-cause mortality (HR=1.11, 95.1% CI [0.96 to 1.27]) based on about 800 observed deaths-Sensitivity analyses that censored subjects after treatment exposure showed more unfavorable trends in the risk of all cause mortality-Such trends were observed for both CV and non-CV related causes of death."…”