Introduction and Objective: Tirzepatide, a dual GIP/GLP-1 receptor agonist, has demonstrated greater glycemic and weight benefits compared with GLP-1 receptor agonists in individual randomized trials. This study aimed to compare the efficacy and safety of tirzepatide versus semaglutide in adults with type 2 diabetes through a systematic review and meta-analysis. Methods: A systematic search of PubMed, Embase, Scopus, and Cochrane CENTRAL (2019-2025) identified randomized controlled trials comparing tirzepatide with semaglutide or allowing indirect comparison through common comparators. Trials enrolling adults ≥18 years with type 2 diabetes and ≥12 weeks’ follow-up were included. Primary outcomes were change in HbA1c and body weight; secondary outcomes included gastrointestinal adverse events and treatment discontinuation. Effect estimates were synthesized using random-effects models. Results: Nine randomized trials (n≈12,500) met inclusion criteria. Tirzepatide achieved greater HbA1c reduction versus semaglutide (pooled mean difference −0.36%, 95% CI −0.42 to −0.30) and significantly greater weight loss (−6.4 kg, 95% CI −7.1 to −5.8). Rates of gastrointestinal adverse events were comparable between groups (risk ratio 1.08, 95% CI 0.97-1.20). No significant differences were observed in severe hypoglycemia or treatment discontinuation across trials. Higher tirzepatide doses (10-15 mg) provided the largest metabolic benefits. Conclusion: Tirzepatide provides significantly greater reductions in HbA1c and body weight compared with semaglutide, with a comparable safety profile. These findings support tirzepatide as a potentially more effective incretin-based therapy for type 2 diabetes. Longer-term studies are needed to assess cardiovascular outcomes and durability of metabolic benefits. Disclosure N. Althubaiti: None.
NASEEM ALTHUBAITI (Fri,) studied this question.