Comparative Efficacy of Tirzepatide and Semaglutide in the Treatment of Obesity: A Meta-analysis

Abstract

Obesity is a chronic and multifactorial disease that imposes a substantial burden of morbidity, mortality, and healthcare costs. Although lifestyle interventions are fundamental, they are often insufficient, highlighting the need for effective pharmacological therapies. This study aimed to technically and quantitatively compare the efficacy of semaglutide (a GLP-1 receptor agonist) and tirzepatide (a dual GIP/GLP-1 receptor agonist) in the treatment of obesity in adults without diabetes. A meta-analysis covering the period from 2021 to 2025 was conducted using the PubMed, Cochrane Library, Web of Science, and Scopus databases. Controlled descriptors and free-text terms related to "obesity," "semaglutide," "tirzepatide," and "clinical trial" were applied. Randomized controlled trials involving adults with overweight or obesity, with or without concomitant behavioral interventions, and reporting weight-loss efficacy outcomes (percentage change and proportions achieving >=5%, >=10%, >=15%, and >=20% weight loss) were included. Observational studies, case series, and studies involving predominantly diabetic populations were excluded, except when obesity-related outcomes were analyzed separately. Study selection followed PRISMA guidelines. Data were extracted using standardized forms and synthesized in tables and forest plots. The results demonstrated that both pharmacological agents promoted clinically meaningful weight loss when combined with lifestyle modifications. Semaglutide achieved mean weight reductions of approximately 15% in longer-term follow-up, whereas tirzepatide showed a greater average magnitude of weight loss (exceeding 20%) and a higher proportion of patients achieving more stringent weight-loss targets. Safety profiles were comparable between treatments and were predominantly characterized by mild to moderate gastrointestinal adverse events. In conclusion, semaglutide and tirzepatide represent significant advances in the pharmacological management of obesity. Based on the evaluated evidence, tirzepatide demonstrated superior average efficacy in weight reduction while maintaining a comparable safety profile, which may help guide therapeutic decision-making according to clinical goals and access considerations.