Clinical outcomes associated with drugs for obesity and overweight: A systematic review and network meta-analysis of randomized controlled trials

Aim: To compare the benefits and harms of drugs approved for weight management in adults with obesity or overweight. Materials and Methods: We performed a systematic review of drugs approved for treating obesity and overweight. We searched MEDLINE, Embase and CENTRAL through 26 February 2023. Random-effects network meta-analysis was applied. Results: A total of 168 trials (97 938 patients) were included. There was no evidence that drugs approved for weight management had different associations with cardiovascular death (69 trials, 59 037 participants). Naltrexone/bupropion was associated with lower cardiovascular mortality than placebo (odds ratio [OR], 0.62 [95% CI: 0.39, 0.99]; low certainty evidence). All drugs were associated with greater weight loss at 12 months than placebo (33 trials, 37 616 participants), mainly semaglutide (mean difference [MD], 9.02 kg [95% CI: 10.42, 7.63]; moderate certainty) and phentermine/topiramate (MD, 8.10 kg [95% CI: 10.14, 6.05]; high certainty); and with greater waist circumference reduction at 12 months than placebo (24 trials, 35 733 participants), mainly semaglutide (MD, 7.84 cm [95% CI: 9.34, 6.34]; moderate certainty) and phentermine/topiramate (MD, 6.20 cm [95% CI: 7.46, 4.94]; high certainty). Semaglutide and phentermine/topiramate were associated with lower or no difference in the odds of treatment withdrawal compared with all other drugs (87 trials, 70 860 participants). Conclusions: Among adults with obesity or overweight, semaglutide and phentermine/ topiramate were associated with greater body weight loss and waist circumference reduction at 12 months than all other drugs, and lower or no significant difference in risks of withdrawal. There was no evidence that drugs approved for weight management had different associations with cardiovascular death.