Semaglutide Outperforms Liraglutide for Weight Loss in Obesity Even Without Diabetes

Semaglutide produced significantly greater weight loss than liraglutide in obese non-diabetic patients, but did not show a significant difference compared to efinopegdutide, with all drugs demonstrating primarily mild-to-moderate GI adverse events.

Systematic review and meta-analysis following PRISMA guidelines. PubMed, Embase, and Cochrane Library were searched for direct comparative studies of semaglutide vs. other GLP-1 RAs (liraglutide, efinopegdutide) in patients with obesity without diabetes. Narrative synthesis and meta-analysis were performed.

Most GLP-1 weight loss data comes from diabetic populations. This meta-analysis confirms semaglutide's superiority over liraglutide specifically in the non-diabetic obesity population — the patient group most likely to seek these drugs purely for weight management.

The obesity drug landscape is evolving rapidly. This study confirms semaglutide as the current gold standard among single-agonist GLP-1 drugs for weight loss in non-diabetic obesity. The comparable results with efinopegdutide are interesting — suggesting that adding glucagon receptor agonism to GLP-1 may not always produce superior weight loss. As tirzepatide, survodutide, and retatrutide join the market, more head-to-head data will clarify which multi-agonist approach works best.

Limited number of direct comparison studies available, especially for efinopegdutide. Study durations and patient populations may vary across included trials. The non-significant difference between semaglutide and efinopegdutide could reflect small sample sizes rather than true equivalence. Long-term weight maintenance data is lacking.