A systematic review and network meta-analysis of 262 randomized trials involving 99,791 participants found that anti-obesity medications vary substantially in both effectiveness and safety, with greater weight loss generally accompanied by higher rates of adverse events and treatment discontinuation. At one year, tirzepatide and cagrilintide-semaglutide (CagriSema) produced the greatest confirmed weight loss (about 15%), followed by oral semaglutide, orforglipron, subcutaneous semaglutide, and phentermine-topiramate, while emerging agents such as ecnoglutide, mazdutide, and retatrutide may achieve similar or even greater reductions, although current evidence remains less certain. However, discontinuation due to adverse events was highest with orforglipron, naltrexone-bupropion, liraglutide, phentermine-topiramate, CagriSema, and oral semaglutide, with gastrointestinal side effects and fatigue being particularly common. Tirzepatide produced the largest reductions in both fat mass and lean mass. Among all therapies, only subcutaneous semaglutide was associated with lower risks of all-cause mortality and myocardial infarction, while both subcutaneous semaglutide and tirzepatide reduced heart failure risk. No medication convincingly reduced kidney failure or produced clinically meaningful improvements in quality of life. Overall, the findings highlight that choosing an obesity medication requires carefully weighing expected weight-loss benefits against potential harms through shared decision-making between clinicians and patients. Source: https://www.bmj.com/
