Comparing semaglutide, liraglutide, orlistat, and phentermine for obesity: a systematic review | Research

The takeaway

A systematic review comparing obesity drugs found all four agents—semaglutide, liraglutide, orlistat, and phentermine—offer distinct weight loss benefits, with GLP-1 agonists showing the strongest efficacy but GI side effects requiring personalized treatment approaches.

Multiple options, different profiles
GLP-1 agonists lead in efficacy, but each obesity drug class offers distinct advantages depending on patient needs and tolerability

What the researchers found

All four agents provide weight loss benefits through distinct mechanisms. GLP-1 agonists (semaglutide, liraglutide) show superior efficacy but cause GI side effects. Orlistat reduces fat absorption with GI discomfort. Phentermine suppresses appetite but has dependency potential. Emerging dual/triple agonists show promise.

Why it matters

With multiple obesity medications now available, clinicians need comparative data to match the right drug to each patient. This review provides a comprehensive comparison to guide personalized treatment selection based on efficacy needs, side effect tolerance, and comorbidity profiles.

The numbers in context

Compares semaglutide, liraglutide, orlistat, phentermine, plus emerging agents: setmelanotide, amycretin, retatrutide, cagrilintide, and cotadutide. Reviews mechanisms, dosing, efficacy, safety, and comorbidity effects.

How the study worked

Systematic literature review comparing mechanisms, dosing, efficacy, safety profiles, and comorbidity impact of semaglutide, liraglutide, orlistat, phentermine, and emerging obesity agents.

Who was studied

Obese individuals

What this study cannot tell us

Literature review without meta-analysis or quantitative pooling. Head-to-head trial data is limited for many comparisons. Emerging agents have less mature evidence. Long-term comparative data is scarce.

How to read the evidence

Systematic review of existing literature. Provides comprehensive overview but without quantitative meta-analysis. Quality depends on underlying studies reviewed.

When this study was published

Published in 2025; includes emerging agents in development pipeline.

The bigger picture

The obesity pharmacotherapy landscape is rapidly expanding, particularly with GLP-1-based peptide drugs. This comparative review helps contextualize where peptide therapies fit among all available options and highlights the growing dominance of incretin-based approaches in weight management.

Questions still open

How do next-generation multi-agonists (retatrutide, amycretin) compare to current best-in-class semaglutide?
Which patient profiles benefit most from non-GLP-1 options like orlistat or phentermine?
What is the optimal duration of pharmacotherapy for sustained weight loss?

Common questions

Which weight loss drug works best?

GLP-1 receptor agonists like semaglutide generally show the greatest weight loss in clinical trials. However, the "best" choice depends on individual factors: some patients may not tolerate GI side effects, may prefer oral medication, or may have conditions that favor one drug over another.

Can weight loss drugs be used long-term?

GLP-1 agonists and orlistat are approved for long-term use, while phentermine is typically for short-term use due to dependency concerns. The review emphasizes that all medications work best when combined with diet and exercise changes for sustainable results.

Read the original research

Comparative Effectiveness of Semaglutide, Liraglutide, Orlistat, and Phentermine for Weight Loss in Obese Individuals: A Systematic Review.

Cureus, 17(3), e80321

View on PubMed ↗Publisher’s paper ↗

Citation

Patel, Jay P; Hardaswani, Daksh; Patel, Jaykumar; Saiyed, Faizanali; Goswami, Rushita J; Saiyed, Taskin I; Patel, Harshkumar; Amin, Trishul H. (2025). Comparative Effectiveness of Semaglutide, Liraglutide, Orlistat, and Phentermine for Weight Loss in Obese Individuals: A Systematic Review.. Cureus, 17(3), e80321. https://doi.org/10.7759/cureus.80321