Background: Heart failure with preserved ejection fraction (HFpEF) is a highly prevalent syndrome among patients with type 2 diabetes mellitus (T2DM), characterized by significant morbidity and mortality. Historically, evidence-based therapies for HFpEF have been limited. Sodium-glucose co-transporter 2 (SGLT2) inhibitors have emerged as a promising therapeutic class, but their specific efficacy in the diabetic HFpEF population requires further elucidation.

Objective: This study aimed to evaluate the efficacy of SGLT2 inhibitors on cardiovascular outcomes, functional status, and renal function in patients with T2DM and HFpEF.

Method: A simulated retrospective cohort study was conducted utilizing synthesized academic training data comprising 420 patients with T2DM and HFpEF. Patients were categorized into an SGLT2 inhibitor group (n=210) and a standard-of-care control group (n=210). The primary endpoint was a composite of cardiovascular death or heart failure hospitalization over a 12-month follow-up period. Secondary endpoints included changes in the Kansas City Cardiomyopathy Questionnaire (KCCQ) score and estimated glomerular filtration rate (eGFR).

Results: The SGLT2 inhibitor group demonstrated a significantly lower risk of the primary composite endpoint compared to the control group (Hazard Ratio [HR] = 0.64, 95% Confidence Interval [CI] = 0.42–0.97, p=0.034). Furthermore, the SGLT2 inhibitor group exhibited a clinically meaningful improvement in KCCQ scores (mean difference: +4.8 points, p=0.001) and a slower decline in eGFR (mean difference: +2.1 mL/min/1.73m², p=0.021) at 12 months.