Pharmacotherapy for overweight and obese adults: a systematic review and network meta-analysis of randomized controlled trials



Drug therapy offers overweight and obese adults an option to reduce their body weight if lifestyle changes fail. We have summarized the latest evidence regarding the pros and cons of weight loss drugs.


This systematic review and network meta-analysis included searches of PubMed, Embase and Cochrane Library (CENTRAL) from inception through March 23, 2021, for randomized controlled trials of weight loss drugs in overweight and obese adults. We performed network frequentist random-effects meta-analyzes to summarize the evidence and applied the frameworks for assessing, developing, and evaluating recommendations to assess the certainty of the evidence, calculate absolute effects, categorize interventions, and present. the results. The study was registered with PROSPERO, CRD 42021245678.


14,605 ​​citations were identified by our search, of which 143 eligible trials recruited 49,810 participants. With the exception of levocarnitine, all drugs reduced body weight compared to the lifestyle modification alone; all of the following numbers refer to comparisons with lifestyle modification. There is high to moderate certainty evidence that phentermine-topiramate is the most effective at reducing weight (odds ratio [OR] weight reduction ≥ 5% 8.02, 95% CI 5.24 to 12.27; mean difference [MD] percentage change in body weight -7.97, 95% CI -9.28 to -6.66) followed by GLP-1 receptor agonists (OR 6.33, 95% CI 5.00 to 8 , 00; MD -576, 95% CI -6.30 to -5.21). Naltrexone-bupropion (OR 2.69, 95% CI 2.11 to 3.43), phentermine-topiramate (2.40, 1.69 to 3.42), GLP-1 receptor agonists (2.17, 1 · 71 to 2.77) and orlistat (1.72, 1.44 to 2.05) were associated with an increase in adverse events leading to discontinuation of treatment. In a post-hoc analysis, semaglutide, a GLP-1 receptor agonist, showed significantly greater benefit than other drugs with a similar risk of adverse events than other drugs for both likelihood of weight loss of 5% or more (OR 9.82, 95% CI 7.09 to 13.61) and percentage change in body weight (MD -11.41, 95% CI -12.54 to – 10.27).


In overweight and obese adults, phentermine-topiramate and GLP-1 receptor agonists have been shown to be the best drugs for reducing weight; of the GLP-1 agonists, semaglutide may be the most effective.


1.3.5 Project for disciplines of excellence, West China Hospital, Sichuan University.