Key result
Tirzepatide cuts MACE-4 risk ~12% vs. dulaglutide in patients with T2D and established ASCVD.
Why the study?
The SURPASS-CVOT trial previously showed tirzepatide was non-inferior to dulaglutide for reducing MACE-3 in patients with type 2 diabetes and established atherosclerotic cardiovascular disease, but differences in expanded cardiovascular outcomes were not fully evaluated.
Does tirzepatide reduce expanded major adverse cardiovascular events (MACE-4 and MACE-5) in patients with type 2 diabetes and established atherosclerotic cardiovascular disease compared to dulaglutide?
RCT
Does tirzepatide reduce expanded major adverse cardiovascular events (MACE-4 and MACE-5) in patients with type 2 diabetes and established atherosclerotic cardiovascular disease compared to dulaglutide?
In patients with type 2 diabetes and established ASCVD, tirzepatide was associated with a significantly lower risk of expanded composite cardiovascular outcomes (MACE-4 and MACE-5) compared to dulaglutide.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“The core clinical implication is that clinicians and patients may prefer tirzepatide or semaglutide over dulaglutide to reduce adverse CV outcomes or death in persons with type 2 diabetes and CVD.”
“People with type 2 diabetes face a significantly higher risk of many other complications, so we wanted to find out how these two medications compared for a broader range of adverse outcomes. In the current analysis, we assessed the effects of tirzepatide on six major complications including heart attack, stroke, coronary procedures such as need for stenting, heart failure, kidney failure and all causes of death. These six complications occurred in 23.7% of patients taking tirzepatide and 27.4% of those taking dulaglutide, a 16% lower risk for tirzepatide, a statistically significant difference.”
“The SURPASS-CVOT study is notable for being the first large-scale cardiovascular outcome trial to use an active comparator—the GLP-1 agonist dulaglutide—rather than a placebo. While previous trials showed tirzepatide was noninferior to dulaglutide for a narrower 3-component cardiovascular end point, this new analysis provides a more 'comprehensive comparison' of the 2 drugs.”
May support broader CV benefit on MACE-4 with tirzepatide; leaves open practice change pending higher-level confirmation.
Objectif Dans SURPASS-CVOT, tirzépatide (TZP) était non-inférieur au dulaglutide (DULA) dans la réduction du risque de MACE (MACE-3 : décès CV, IM ou AVC) chez des patients vivant avec un DT2 et une maladie cardiovasculaire athérosclérotique (MCVAS) établie. L’analyse évalue les différences dans les résultats CV élargis. Patients et méthodes Dans ces analyses préspécifiées, l’effet du TZP (≤ 15 mg) vs DULA (1,5 mg) sur les MACE-4 (décès CV, IM, AVC ou revascularisation coronarienne) et les MACE-5 (MACE-4 ou hospitalisation pour angor instable [AI]) a été analysé. Résultats Un MACE-4 est survenu chez 1089 patients (16,5 %) recevant TZP vs 1217 (18,5 %) recevant DULA (RR 0,88 ; IC95 % ; 0,81–0,96). Chez les patients ayant des antécédents de maladie coronarienne (MC) : un MACE-4 est survenu chez 875 (18,6 %) patients traités par TZP vs 967 (20,5 %) par DULA (RR 0,89 ; IC95 % ; 0,81-0,97). Patients sans antécédents MC : MACE-4 chez 214 (11,3 %) TZP et 250 (13,3 %) DULA (RR 0,84 ; IC95 % ; 0,70–1,01). MACE-5 chez 1112 (16,9 %) TZP et 1240 (18,8 %) DULA (RR 0,88 ; IC95 % ; 0,81–0,96). Revascularisation coronaire chez 527 (8,0 %) vs 617 (9,4 %) (RR 0,84 ; IC95 % ; 0,75–0,95). Hospitalisation pour AI chez 110 (1,7 %) vs 148 (2,2 %) (RR 0,74 ; IC95 % ; 0,57–0,94). Discussion Chez les patients vivant avec un DT2 et une MCVAS, TZP était associé à un risque plus faible de MACE-4, de MACE-5, de revascularisation coronarienne et d’hospitalisation pour AI que DULA.
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Bleis et al. (2026) conducted an RCT in Type 2 diabetes and established atherosclerotic cardiovascular disease. Tirzepatide vs. Dulaglutide (1.5 mg) was evaluated on MACE-4 (CV death, MI, stroke, or coronary revascularization) (RR 0.88, 95% CI 0.81-0.96).
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