GLP-1 Receptor Agonist in Non-obese Patients with Type-2 Diabetes Mellitus and Heart Failure with Preserved Ejection Fraction.

Background: Glucagon like peptide-1 receptor agonists (GLP-1RA) promote weight loss and improve heart failure-related symptoms, quality of life, and functional capacity in patients with obesity and heart failure with preserved ejection fraction (HFpEF). However, their clinical effectiveness in non-obese patients with diabetes and HFpEF is understudied.

Methods: The TriNetX research network was used to identify adult patients (≥18 years) with type 2 diabetes mellitus (T2DM), Heart failure with preserved ejection fraction ((Left ventricular ejection fraction ≥45%), elevated brain natriuretic peptide (≥150pg/mL) or N-terminal pro-B-type natriuretic peptide(≥450pg/mL) and a body mass index (BMI) <30 kg/m2 on or before August 31, 2022. Patients were divided into two groups based on GLP-1RA use. After propensity score matching, Cox proportional Hazard Ratios (HRs) were used to compare outcomes over a 12-month follow-up period.

Results: The study included 84,990 patients (n= 42,495 per group, mean age 64 years, 49% females, 65% white). Patients on GLP-1RA were associated with lower incidence of heart failure exacerbation events (HR 0.60, 95% CI 0.58-0.62, p<0.001) and all-cause emergency room visits or hospitalizations (HR 0.67, 95% CI 0.66-0.69, p<0.001) compared to those not on GLP-1RA. Other outcomes including acute myocardial infarction, atrial fibrillation, ischemic stroke, pulmonary hypertension, C-reactive protein ≥5mg/L, acute kidney injury, and the need for renal replacement therapy, were also significantly less frequent in the GLP-1RA group. These associated benefits persisted even among patients on sodium-glucose cotransporter-2 inhibitors (SGLT2i).

Conclusion: GLP-1RA use is associated with improved cardiovascular outcomes in non-obese patients with T2DM and HFpEF and has an associated incremental benefit even among patients on SGLT2i.