Presentation (CTI)

OBJECTIVES: Semaglutide and tirzepatide are widely used obesity management medications with substantial effects on percentage total body weight loss (TBWL%). Recent approval of oral semaglutide (25mg/day) and availability of higher-dose subcutaneous (SC) semaglutide (7.2mg) has further expanded the treatment landscape. Comparative evidence is challenging due to variations in trial follow-up time, which limits the utility of conventional timepoint-specific network meta-analysis. We therefore used a time-course model-based NMA (MBNMA) to compare semaglutide and tirzepatide for TBWL% in adults with obesity.
METHODS: Trial data for TBWL% at multiple follow-up time points were obtained from an existing systematic review conducted up to January 2026. Longitudinal effect was modelled using Bayesian MBNMA with a linear fractional polynomial time function to estimate relative treatment effects across interventions. Treatment effects were modelled on the absolute scale (identity link) and extrapolated to two years to predict long-term weight-loss trajectories. A random-effects model was used as a priori model.
RESULTS: Over two years, both interventions achieved clinically meaningful TBWL% (>10%) versus placebo. Weight loss trajectories plateaued after approximately 72 weeks, suggesting sustained benefits till two years. Semaglutide 2.4mg SC showed TBWL% of 11.7% (95% credible intervals [CrI]: 10.1,13.2), followed by semaglutide 25mg oral (12.8% [5.7,19.6]), and semaglutide 7.2mg SC (14.0% [9.9,18.1]). Tirzepatide 10-15mg SC demonstrated the largest effect with a TBWL% of 17.7% (15.5,19.9). However, there was a considerable overlap in the CrIs across higher doses of semaglutide and tirzepatide 10-15mg, indicating no evidence of a significant difference between these treatments.
CONCLUSIONS: In this time-course MBNMA, higher-dose semaglutide narrowed the efficacy gap versus tirzepatide for TBWL% over two years, with overlapping CrIs between treatments. These findings provide robust comparative evidence to guide long-term obesity management and dose selection, emphasizing the potential of higher-dose semaglutide and tirzepatide for maximizing treatment efficacy.