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

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.

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/m² 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.

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%).

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.