Glucagon‐Like Peptide‐1 Receptor Agonists in Obese Heart Failure With Preserved Ejection Fraction

Background To evaluate whether GLP‐1 (glucagon‐like peptide‐1) receptor agonists (GLP‐1RAs), compared with DPP4 (dipeptidyl peptidase‐4) inhibitors or sulfonylureas, are associated with reduced all‐cause mortality or heart failure hospitalizations in patients with obesity and type 2 diabetes, and heart failure with preserved ejection fraction. Methods PRAISE‐HFpEF (Glucagon‐Like Peptide‐1 Receptor Agonist in Obese Heart Failure With Preserved Ejection Fraction) was a nationwide multicenter cohort study using a new‐user, active‐comparator design within the national Veterans Affairs Health System (170 US hospitals). Adults with type 2 diabetes between January 1, 2000 and December 31, 2021, were identified from centralized electronic health records. Patients with heart failure with preserved ejection fraction and a body mass index ≥30 kg/m 2 were selected using a validated diagnostic algorithm. Exposure was initiation of a GLP‐1RA versus DPP4 inhibitors/sulfonylurea from January 1, 2015 to December 31, 2021. The primary outcome was time to all‐cause mortality or heart failure hospitalization. Inverse probability of treatment weighting based on the propensity score was used to balanced baseline characteristics. Results Among 179 288 patients with type 2 diabetes, obesity, and heart failure with preserved ejection fraction, 1024 GLP‐1RA users and 796 DPP4 inhibitors/sulfonylurea users met inclusion criteria. Over a median follow‐up of 1.5 years, GLP‐1RA use was associated with a lower risk of the primary outcome (adjusted hazard ratio, 0.78 [95% CI, 0.64–0.95], P =0.01). Weight loss was modestly greater with GLP‐1RAs compared with DPP4 inhibitors/sulfonylurea (−12.9% versus −10.1%). Conclusions Among patients with obese heart failure with preserved ejection fraction and type 2 diabetes, GLP‐1RA initiation was associated with a lower incidence of death or heart failure hospitalization compared with alternative oral agents.