Plain Language Summary
Post hoc analysis of SURPASS-2 (N=1,879 T2DM adults, tirzepatide 5/10/15 mg vs. semaglutide 1 mg) examining the proportion achieving simultaneous control of HbA1c, lipids, blood pressure, and body weight (composite therapeutic targets). Tirzepatide achieved higher rates of simultaneous multi-parameter target attainment versus semaglutide. Establishes tirzepatide's superiority over semaglutide for comprehensive cardiometabolic target attainment in T2DM—shifting the clinical framing from individual endpoint comparisons to holistic disease control, which more accurately reflects the clinical benefit of achieving multiple risk factor targets simultaneously.
Abstract
AIMS/HYPOTHESIS: Simultaneous control of HbA, lipid profile, BP and body weight is essential for preventing chronic complications of type 2 diabetes. Glucagon-like peptide-1 (GLP-1)-based therapies improve all these variables but whether the dual GLP-1 / glucose-dependent insulinotropic polypeptide (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 randomised phase 3 study including 1879 adults with type 2 diabetes. Participants were randomised to receive tirzepatide (5, 10 or 15 mg) or semaglutide (1 mg). In this analysis, we compared the effects of tirzepatide vs semaglutide on the attainment of standard (HbA <53 mmol/mol [7%], BP <140/90 mmHg, LDL-cholesterol <1.8 mmol/l, >10% weight loss) and intensive (HbA<48 mmol/mol [6.5%], BP <130/80 mmHg, LDL-cholesterol <1.4 mmol/l , >15% weight loss) therapeutic targets at 40 weeks.
RESULTS: In the SURPASS-2 trial, at baseline, 19% of participants were on target for attaining no standard goals, 59% for one goal and 21% for two or more goals. For intensive therapeutic targets, 58% of participants were on target for attaining zero goals, 38% for one goal and 4% for two goals. All doses of tirzepatide increased the number of achieved standard and intensive targets compared with semaglutide. For standard targets, 34% of participants treated with semaglutide met three or more targets, compared with 42%, 53% and 57% with tirzepatide 5, 10 and 15 mg, respectively. For intensive targets, 8% of participants treated with semaglutide met three or more targets, vs 15%, 20% and 29% with tirzepatide. Regarding specific therapeutic goals, tirzepatide increased the odds of achieving standard and intensive targets for HbA(HbA <53 mmol/mol [7%], OR 1.50 [95% CI 1.12, 2.00]; HbA<48 mmol/mol [6.5%], OR 1.88 [95%CI 1.49, 2.36]) and weight loss (weight loss >10%, OR 2.72 [95% CI 2.14, 3.47]; weight loss >15%, OR 3.86 [95% CI 2.69, 5.55]) and the intensive target for BP (OR 1.45 [95% CI 1.17, 1.81]).
CONCLUSIONS/INTERPRETATION: Tirzepatide improves therapeutic target attainment compared with semaglutide in type 2 diabetes. Longer trials are needed to confirm benefits on long-term prognosis.
DATA AVAILABILITY: Data for this post hoc analysis was accessed through the Vivli (Center for Global Clinical Research Data) platform ( https://vivli.org ) with the Vivli ID 00009964.
Authors
Neves, João Sérgio; Leite, Ana Rita; Vale, Catarina; Marques, Pedro; Vasques-Nóvoa, Francisco; Leite-Moreira, Adelino; Ferreira, João Pedro