Network Meta-Analysis Finds Tirzepatide and Sleeve Gastrectomy Equally Effective for Weight Loss in Obesity

This network meta-analysis and systematic review compared the efficacy and safety of sleeve gastrectomy (SG), tirzepatide, semaglutide, liraglutide, and orlistat for weight loss in adults with obesity. The analysis included 14,293 participants from multiple randomized controlled trials with follow-up of at least 24 weeks. The primary outcome was percentage change in total body weight (TWL).

Sleeve gastrectomy and tirzepatide 10 or 15 mg demonstrated statistically equivalent weight-loss efficacy. The mean difference (MD) for SG was 21.1% TWL (95% CI 14.2% to 28.0%), and for tirzepatide 10 or 15 mg it was 21.3% TWL (95% CI 17.3% to 25.2%), with a P-score of 0.84. Semaglutide 2.4 mg showed moderate efficacy with an MD of 12.7% TWL, and liraglutide 3.0 mg had an MD of 5.1% TWL. Orlistat demonstrated minimal effect with an MD of 2.7% TWL (95% CI -4.2% to 9.6%).

Regarding safety, the network meta-analysis indicated that semaglutide 2.4 mg and orlistat had the most favorable safety profiles among the pharmacotherapies. However, serious adverse events, discontinuation rates, and tolerability were not reported in the analysis. The safety comparison between surgical and medical interventions was not directly assessed.

Compared to prior landmark studies, these findings align with individual trials showing tirzepatide's superior efficacy over other GLP-1 receptor agonists. The equivalence between tirzepatide and SG is notable, as surgery has traditionally been the most effective intervention for severe obesity. However, this analysis does not account for long-term durability of weight loss, which is a key advantage of surgical approaches.

Key methodological limitations include the absence of reported heterogeneity or inconsistency assessments, potential publication bias, and the lack of individual patient data. The analysis also did not adjust for baseline characteristics such as diabetes status or obesity class, which may influence treatment response. Additionally, the follow-up duration of at least 24 weeks is relatively short for obesity interventions, and longer-term outcomes remain unknown.

Clinically, these results suggest that tirzepatide 10 or 15 mg can achieve weight loss comparable to sleeve gastrectomy in the short term, offering a potent non-surgical alternative for patients with obesity. However, clinicians should consider that surgery may provide more sustained weight loss and additional metabolic benefits. The moderate efficacy of semaglutide and liraglutide supports their use as second-line options, while orlistat's minimal effect limits its role.

Unanswered questions include the long-term comparative effectiveness beyond 24 weeks, the impact on obesity-related comorbidities, and the safety profile of tirzepatide versus surgery over extended periods. Future studies should also evaluate patient subgroups and cost-effectiveness to guide personalized treatment decisions.