Tirzepatide versus dulaglutide in heart failure: another SURPASS attempt yielding a tie

Heart failure (HF) is a major driver of morbidity in individuals with type 2 diabetes (T2D). While incretin-based therapies consistently reduce atherosclerotic cardiovascular (CV) events, their impact on HF outcomes remains uncertain. The SURPASS-CVOT (Comparison of tirzepatide and dulaglutide on major adverse CV events in participants with T2D and atherosclerotic disease), the first CV outcome trial directly comparing the dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonists receptor agonist (GIP/GLP-1 RAs) tirzepatide with the selective GLP-1 RA dulaglutide, demonstrated noninferiority of tirzepatide for 3-point major adverse CV events (MACE), with greater metabolic and renal benefits. In the prespecified HF subgroup (20% of the trial population, defined according to investigator-reported medical history), tirzepatide reproduced the larger metabolic and renal benefits observed in the overall cohort, including greater weight loss, superior glycemic control, and a slower decline in renal function compared with dulaglutide, with similar effects in participants with and without HF. Tirzepatide was non inferior to dulaglutide for 3-point MACE irrespective of HF history. No differences were observed between treatment groups for composite HF endpoints (all-cause death or HF events; CV death or HF events) or HF events alone, both in participants with and without HF. However, as the trial was not powered for comparisons within the HF subgroup and HF endpoints were not included in the multiplicity-controlled testing hierarchy, these findings should be considered exploratory. This meeting report critically examines the SURPASS-CVOT HF subanalysis and place its results within the broader evidence on incretin-based therapies in patients with HF.