Network meta-analysis of GLP-1 therapies for obesity

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Created On: 19/02/2026

This study determined the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP RAs), specifically semaglutide and liraglutide, for weight loss in adults with obesity or overweight.

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Key take away

Among GLP-1 receptor agonists, semaglutide 2.4 mg leads in weight reduction and glycemic control but carries increased safety risks.

Background

This study determined the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP RAs), specifically semaglutide and liraglutide, for weight loss in adults with obesity or overweight. The objective was to provide evidence-based clinical guidance for obesity management and metabolic health improvement.

Method

An extensive search of Cochrane Library, PubMed, and Embase determined randomized controlled trials (RCTs) exploring semaglutide or liraglutide injection monotherapy. A network meta-analysis using Stata 16 was conducted to compare multiple dosages across efficacy and safety endpoints. Continuous data were analyzed via mean difference (MD), with results reported as 95% confidence intervals.

Result

In this systematic review, 23 RCTs involving 11,545 volunteers and 4 GLP-1RA dosing regimens—semaglutide 2.4 mg, semaglutide 1.0 mg, liraglutide 3.0 mg, and liraglutide 1.8 mg—were included. For weight reduction, semaglutide 2.4 mg illustrated the greatest effect (−12.47 kg), followed by liraglutide 3.0 mg (−5.24 kg), semaglutide 1.0 mg (−3.74 kg), and liraglutide 1.8 mg (−3.29 kg).

Regarding glycemic control, remarkable hemoglobin A1c (HbA1c) reductions were noted with semaglutide 2.4 mg (−1.48%), semaglutide 1.0 mg (−1.36%), and liraglutide 1.8 mg (−1.23%) compared with placebo. Regarding safety, the overall incidence of adverse events was found to be greatest with semaglutide 2.4 mg, followed by liraglutide 3.0 mg, liraglutide 1.8 mg, and semaglutide 1.0 mg. Serious adverse events occurred most frequently with liraglutide 3.0 mg, while hypoglycemic episodes were more commonly associated with semaglutide 2.4 mg.

Conclusion

GLP-1 RAs were considerably more effective than placebo for weight loss and HbA1c reduction in individuals with overweight or obesity. Semaglutide 2.4 mg offered superior weight-loss and glycemic benefits, although it was linked to a higher incidence of adverse and hypoglycemic events. While liraglutide 3.0 mg showed moderate efficacy, it was linked with the highest risk of serious adverse events, highlighting the importance of individualized treatment selection in obesity care.