Comparative Effectiveness of Semaglutide, Orforglipron, Phentermine–Topiramate, and Naltrexone–Bupropion for the Management of Overweight and Obesity: A Network Meta-analysis of Randomized Clinical Trials

Oral anti-obesity pharmacotherapies have become an integral component of weight management strategies. Several studies have established the efficacy and safety of currently available oral agents, including semaglutide, phentermine–topiramate, and naltrexone–bupropion. However, orforglipron, a novel oral non-peptide GLP-1 receptor agonist, represents a recent therapeutic advance for which comparative evidence against established oral treatments remains limited. Accordingly, this study aims to systematically compare the efficacy and safety of these oral pharmacotherapies through a network meta-analysis of randomized clinical trials.