Recent obesity pharmacotherapy centers on established non- drugs, GLP-1 and GLP-1/GIP agents, and newer incretin and amylin-based candidates.
Evidence
This narrative review summarizes FDA-approved anti-obesity medications and selected Phase 2 and 3 drugs under development as of February 2025.
Caveat
Because it is a narrative review, its comparisons and practice advice depend on the selected literature rather than a new systematic analysis or trial.
Simplified
In this narrative review we describe the recent updates regarding anti-obesity medications as of February 2025. We describe the physiologic mechanisms underpinning the development of hunger, satiation, and maintenance of satiety to address targets for anti-obesity medications. The efficacy, mechanism, and additional beneficial effects of anti-obesity medications are then further detailed. For this review, we focus on FDA-approved medications for obesity and on select medications currently under development and undergoing Phase 2 and 3 trials. We start by focusing on the non- anti-obesity medications orlistat, phentermine, phentermine-topiramate, and naltrexone-bupropion. We also highlight setmelanotide for heritable obesity. The mechanism of action and comparative efficacy of the liraglutide and semaglutide are reviewed. Tirzepatide, the GLP-1 and GIP-receptor dual agonist is described, and weight loss is compared to alternative anti-obesity medications. Additional incretin targets in the pipeline include dual co-agonists to glucagon and GLP-1 receptors, triple agonists targeting glucagon, GLP-1 and GIP, novel GLP-1 agonists, oral formulations of GLP-1 agonists, and amylin agonists. Finally, we provide best practices for adjuncts to pharmacologic treatments of obesity, monitoring efficacy of obesity treatments, and adjusting medication regimens for providers.
Key numbers
−10.92%
Weight Loss with Phentermine-Topiramate
Weight loss compared to −1.55% in placebo at 56 weeks.
−14.9%
Weight Loss with Semaglutide
Weight loss compared to −2.4% with placebo at 68 weeks.
−20.9%
Weight Loss with Tirzepatide
Mean weight loss at 15 mg weekly compared to −3.1% with placebo.
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2 authors disclosed relationships: one reported stock options, research grants, and consulting; the other reported consulting fees, funding support, and institution-to-company patent licenses involving Phenomix Sciences and Gila Therapeutics.
