OR19-05 Efficacy of Tirzepatide versus Semaglutide in Achieving Therapeutic Targets in Type 2 Diabetes: a post hoc analysis of SURPASS-2 Trial

Abstract Disclosure: A.R. Leite: reports having received consulting fees from BIAL. J. Neves: reports having received consulting or speaker fees from AstraZeneca, Bayer, BIAL, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Menarini and Merck. C. Vale: None. A. Leite-Moreira: None. J. Ferreira: receives research support from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Novartis and Salamandra. Introduction: Simultaneous control of glycated hemoglobin (HbA1c), lipid profile, blood pressure (BP), and body weight is essential for preventing chronic complications of type 2 diabetes (T2D). GLP-1-based therapies improve all these parameters, but whether the dual GLP-1/GIP agonist tirzepatide is superior to semaglutide in attaining therapeutic targets remains unclear. Methods: We performed a post-hoc analysis of the SURPASS-2 trial, a randomized, open label, multicentre, parallel-group phase 3 trial that enrolled 1,879 patients with T2D to compare the effects of tirzepatide (5 mg, 10 mg, and 15 mg) versus semaglutide (1 mg) on the change in HbA1c levels from baseline to 40 weeks. In this analysis, we compared the effects of tirzepatide versus semaglutide in the attainment of standard and intensive therapeutic targets, defined according to the Standards of Care in Diabetes from the American Diabetes Association. Standard targets included HbA1c <7.0%, BP <140/90 mmHg, LDL-cholesterol <70 mg/dL, and >10% weight loss. Intensive targets included HbA1c <6.5%, BP <130/80 mmHg, LDL cholesterol <55 mg/dL, and >15% weight loss. The mean number of goals achieved in the tirzepatide versus semaglutide groups were compared using linear regression analysis. Ordered logistic regression models were used to evaluate the effects of tirzepatide (pooled 5mg, 10mg, and 15mg doses) versus semaglutide 1.0 mg on the attainment of therapeutic goals at 40 weeks. A two-sided P-value <0.05 was considered statistically significant. Results: In this SURPASS-2 analysis including 1,759 participants (mean age 56.6±10.4 years, 53% female, HbA1c 8.3±1.0%, and BMI 34.2±6.9 kg/m²), the mean number of targets achieved at baseline was 1.1 ± 0.7 for standard targets and 0.5 ± 0.6 for intensive targets. Tirzepatide significantly increased the number of achieved standard (2.2 ± 0.9 with semaglutide vs 2.3 ± 1.0, 2.5 ± 1.0, and 2.6 ± 1.0 with tirzepatide 5, 10, and 15 mg, p<0.001) and intensive goals (1.3±0.9 with semaglutide vs 1.5±0.9, 1.7±1.0, and 1.9±1.1 with tirzepatide 5, 10, and 15 mg, p<0.001). For standard targets, 35% of participants treated with semaglutide met ≥3 targets, compared to 42%, 53%, and 57% with tirzepatide 5, 10, and 15 mg (OR for pooled tirzepatide vs semaglutide = 1.91, 95%CI 1.53-2.40; p<0.001). For intensive targets, 8% of participants treated with semaglutide met ≥3 targets, compared to 15%, 20%, and 29% with tirzepatide (OR = 3.09, 95%CI 2.14-4.45; p<0.001). Conclusions: Tirzepatide is superior to semaglutide in attaining standard and intensive therapeutic targets in T2D, potentially improving long-term prognosis. Longer clinical trials are required to confirm the potential benefits on hard clinical outcomes. Presentation: Sunday, July 13, 2025