Key result
Tirzepatide cuts death or heart failure events ~17% vs. dulaglutide in patients with HF.
Why the study?
The impact of tirzepatide and dulaglutide on major adverse cardiovascular events and heart failure outcomes according to heart failure status was unknown.
Does tirzepatide improve cardiovascular and heart failure outcomes compared to dulaglutide in patients with type 2 diabetes and atherosclerotic cardiovascular disease?
RCT
Does tirzepatide improve cardiovascular and heart failure outcomes compared to dulaglutide in patients with type 2 diabetes and atherosclerotic cardiovascular disease?
Hazard Ratio: 0.83 (95% CI 0.7–0.99)
Tirzepatide may lower the rates of all-cause death or heart failure events and MACE-4 compared to dulaglutide in patients with type 2 diabetes, atherosclerotic cardiovascular disease, and a history of heart failure.
May support tirzepatide preference in T2D with HF and ASCVD; extends SURPASS-CVOT but remains hypothesis-generating.
AIMS: The impact of tirzepatide and dulaglutide on major adverse cardiovascular events (MACE) and heart failure (HF) outcomes according to HF status is unknown. METHODS AND RESULTS: Patients with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease were treated with tirzepatide up to 15 mg or dulaglutide 1.5 mg weekly (average 4 years). The incidence of MACE-3 [cardiovascular (CV) death, myocardial infarction (MI), stroke], MACE-4 (CV death, MI, stroke, coronary revascularization) and composite of all-cause or CV death and hospitalization or urgent visits for HF were analysed in patients with and without a history of HF. A history of HF (20.3%) was associated with more coronary artery disease and prior MI. Incidences of event categories were higher in the HF group. The hazard ratio (HR) for all-cause death or hospitalization or urgent visits for HF on tirzepatide vs. dulaglutide was 0.83 [95% confidence interval (CI) 0.70-0.99] in patients with HF and 0.88 (95%CI 0.78-1.00) without HF. The HR for CV death or hospitalization or urgent visits for HF was 0.85 (95%CI 0.70-1.03) and 0.96 (95%CI 0.83-1.12), for MACE-3 0.90 (95%CI 0.76-1.08) and 0.93 (95%CI 0.83-1.04), and for MACE-4 0.81 (95%CI 0.69-0.95) and 0.91 (95%CI 0.83-1.00) in patients with and without HF, respectively. The patient-reported outcomes of APPADL and EQ-5D-5L visual analogue scores improved and were higher on tirzepatide in both groups. CONCLUSION: With overall non-inferiority established, this exploratory analysis revealed lower rates of the composite of all-cause death or HF events, or MACE-4 among patients with T2D and HF treated with tirzepatide compared with dulaglutide.
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Nicholls et al. (2026) conducted an RCT in Type 2 diabetes and atherosclerotic cardiovascular disease. Tirzepatide vs. Dulaglutide 1.5 mg weekly was evaluated on Composite of all-cause death or hospitalization or urgent visits for heart failure in patients with HF (HR 0.83, 95% CI 0.70-0.99). Tirzepatide lowered the risk of all-cause death or heart failure events compared with dulaglutide in patients with type 2 diabetes and a history of heart failure (HR 0.83; 95% CI 0.70-0.99).
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