Shi Q, Wang Y, Hao Q, et al. - The best weight-lowering drugs in adults with overweight and obesity include phentermine–topiramate and GLP-1 receptor agonists; of the GLP-1 agonists, semaglutide might represent the most effective.

• In this systematic review and network meta-analysis, relevant randomized controlled trials (n=143 with 49,810 participants) from PubMed, Embase, and Cochrane Library (CENTRAL) were included to summarize the latest evidence for the advantages and harms of weight-lowering drugs.

• Reduction of body weight was achieved with all drugs, except for levocarnitine, vs lifestyle modification alone.

• By high to moderate certainty evidence, phentermine–topiramate was the most effective in decreasing weight (odds ratio [OR] of ≥5% weight reduction 8·02) followed by GLP-1 receptor agonists (OR 6·33).

• Drugs that were linked with increased adverse events (resulting in medication discontinuation) were: naltrexone–bupropion (OR 2·69), phentermine–topiramate (2·40), GLP-1 receptor agonists (2·17), and orlistat (1·72).

• A post-hoc analysis revealed substantially larger benefits with semaglutide (a GLP-1 receptor agonist), for both probability of weight loss of 5% or more (OR 9·82) and percentage bodyweight change (MD −11·41), relative to other drugs with a similar risk of adverse events as other drugs.