Glucagon-Like Peptide-1 Receptor Agonists Promote Weight Loss 

According to the World Health Organisation Fact Sheet on obesity and overweight, 1.5 billion adults are overweight, and 500 million adults are obese. Glucagon-like peptide-1 (GLP-1), which is secreted from the intestine, enhances endogenous insulin secretion after meal ingestion, inhibits glucagon secretion, suppresses food intake, and suppresses appetite.

This systematic review and meta-analysis by Visboll and colleagues assesses the effects of treatment with GLP-1 receptor (GLP-1R) agonists in overweight or obese adults with or without type 2 diabetes mellitus.

Patients treated with GLP-1R agonists exhibited greater weight loss and improved blood pressure and cholesterol levels irrespective of the presence of type 2 diabetes, according to the findings of a systematic review and meta-analysis.

The authors mention the difficulties people have in achieving and maintaining weight loss, suggesting that new treatments are required. "Meta-analyses of clinical trials on non-pharmacological strategies for weight reduction have reported 1-6 kg losses that have been difficult to maintain," the authors write. "Meta-analyses of sibutramine and orlistat trials report average weight reductions of 3 kg to 5 kg, but some of the included trials had attrition rates of up to 50% that were possibly due to adverse events, suggesting that the interventions could be less effective in clinical practice."

In the random effects meta-analysis, patients who received GLP-1R agonists exhibited greater weight loss (weighted mean change in body weight, −2.9 kg; 95% confidence interval [CI], −3.6 to −2.2) than patients who received placebo, oral antidiabetic drugs, or insulin, with the greatest weight loss associated with higher doses of GLP-1R agonists.

In this study, the authors searched the Cochrane Library, Medline, Embase, and Web of Science databases for studies that included GLP-1R agonists. The authors included 25 randomized controlled trials (10,560 total participants) in which patients were administered GLP-1R agonists (liraglutide or exenatide) for a minimum of 20 weeks.

Evidence of intertrial heterogeneity was found in the analysis (τ², 2.4; P < .01). Weight reduction was observed in patients both without (weighted mean difference, −3.2 kg; 95% CI, −4.3 to −2.1) and with (weighted mean difference, −2.8 kg; 95% CI, −3.4 to −2.3) diabetes.

In the fixed-effects meta-analysis, no clear evidence of bias or small study effects were observed (P > .01 for all analyses). In the subgroup analysis, patients receiving exenatide twice daily (−2.8 kg; 95% CI, −2.9 to −2.7 kg), exenatide once weekly (−2.8 kg; 95% CI, −5.2 to −0.3 kg), or liraglutide (−2.2 kg; 95% CI, −3.5 to −0.9 kg) exhibited weight reduction. Additional analysis indicated that GLP-1R agonists improved systolic and diastolic blood pressure, plasma cholesterol levels, and glycemic control.

The authors suggest that their findings indicate the clinical utility of GLP-1R agonists in treating obesity. "The present meta-analysis provides convincing evidence that GLP-1R agonists, when given to obese patients with or without diabetes, results in clinically relevant beneficial effects on body weight," the authors write. "Additional beneficial effects on blood pressure and total cholesterol might also be achieved."

Raj Padwal, MD, from the Walter C. Mackenzie Health Sciences Centre in Edmonton, Canada, notes that despite the findings of the present study, current clinical practice should not be changed. "Modification of diet and lifestyle remains the cornerstone of the treatment of type 2 diabetes," Dr. Padwal writes. "On the basis of current evidence, off label use of GLP-1-agonists for weight loss in people without diabetes cannot be recommended at this time."

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MEDSCAPE