Meta-analysis found semaglutide produced significantly greater weight loss than liraglutide in patients with obesity without diabetes, while showing comparable results to the dual-agonist efinopegdutide.
Semaglutide > liraglutideSignificantly greater weight loss with semaglutide in non-diabetic obese patients — confirming it as the top single-agonist GLP-1 drug for this population
What the researchers found
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.
Why it matters
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 numbers in context
Direct comparison data analyzed for semaglutide versus liraglutide and efinopegdutide in non-diabetic obesity.
How the study worked
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.
Who was studied
Adults with obesity without type 2 diabetes
What this study cannot tell us
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.
How to read the evidence
Moderate evidence from a systematic review and meta-analysis of direct comparison studies, limited by the small number of available head-to-head trials in non-diabetic obesity populations.
When this study was published
Published in 2024, providing timely comparisons as GLP-1 drug use for weight management continues to expand rapidly.
The bigger picture
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.
Questions still open
- Will tirzepatide and retatrutide significantly outperform semaglutide for weight loss in non-diabetic obesity?
- Does semaglutide's weight loss advantage over liraglutide translate into better long-term metabolic outcomes?
- What is the optimal GLP-1 drug choice for patients prioritizing weight loss alone vs. metabolic health broadly?
Common questions
Is semaglutide better than liraglutide for weight loss if I don't have diabetes?
What is efinopegdutide and how does it compare?
Read the original research
Comparative Efficacy of Semaglutide Versus Liraglutide or Efinopegdutide on Weight Loss in Obese Patients: A Systematic Review and Meta-Analysis.
Cureus, 16(12), e75304
Citation
Wen, Jimmy; How-Volkman, Christiane; Truong, Alina; Nadora, Denise; Bernstein, Ethan M; Akhtar, Muzammil; Puglisi, Jose; Frezza, Eldo. (2024). Comparative Efficacy of Semaglutide Versus Liraglutide or Efinopegdutide on Weight Loss in Obese Patients: A Systematic Review and Meta-Analysis.. Cureus, 16(12), e75304. https://doi.org/10.7759/cureus.75304