Clinical bottom line
Sodium-glucose co-transporter-2 (SGLT2) inhibitors represent a promising therapeutic option for older adults with heart failure with preserved ejection fraction (HFpEF), demonstrating benefits in reducing heart failure hospitalizations and improving quality of life. Recent trials and meta-analyses suggest that empagliflozin and dapagliflozin confer cardiovascular benefits in this population, including those with multiple comorbidities typical of geriatric patients. However, the heterogeneity of HFpEF pathophysiology in older adults and limited long-term safety data warrant cautious individualized use alongside comprehensive management (Bu et al., 2025; Hashemi et al., 2025).
What the evidence shows
HFpEF is highly prevalent in older adults and is characterized by complex metabolic and inflammatory alterations that contribute to diastolic dysfunction and exercise intolerance (Ye et al., 2026). SGLT2 inhibitors, originally developed for diabetes, have demonstrated cardiovascular benefits beyond glycemic control, including natriuresis, blood pressure reduction, and improved myocardial energetics.
The EMPEROR-Preserved trial and subsequent analyses reported that empagliflozin significantly reduced the composite endpoint of cardiovascular death or heart failure hospitalization in patients with HFpEF, with consistent effects observed in older subgroups (Wagdy et al., 2021; Bu et al., 2025). Similarly, dapagliflozin showed favorable outcomes in reducing heart failure events in HFpEF patients, including those without diabetes (Bu et al., 2025).
Meta-analyses comparing SGLT2 inhibitors to glucagon-like peptide-1 receptor agonists in diabetic patients with HFpEF suggest superior efficacy of SGLT2 inhibitors in reducing heart failure hospitalizations (Albulushi et al., 2024). Pharmacologic reviews emphasize that SGLT2 inhibitors are generally well tolerated in older adults, with a low risk of hypoglycemia and manageable side effects (Hashemi et al., 2025; Hias et al., 2022).
Caveats and uncertainty
Despite encouraging results, HFpEF remains a heterogeneous syndrome with diverse phenotypes, especially in older adults with multiple comorbidities such as frailty, renal impairment, and polypharmacy, which may influence treatment response and safety (Ye et al., 2026; Hashemi et al., 2025).
Long-term data on SGLT2 inhibitor safety and efficacy in the geriatric population are limited. Potential adverse effects, including volume depletion, genitourinary infections, and rare ketoacidosis, require careful monitoring (Hias et al., 2022).
Most clinical trials enrolled patients with relatively preserved renal function and excluded those with severe frailty or cognitive impairment, limiting generalizability to the broader elderly population (Bu et al., 2025). Additionally, the impact of SGLT2 inhibitors on functional status and quality of life in frail older adults warrants further investigation.
How this may change practice
Clinicians managing older adults with HFpEF should consider SGLT2 inhibitors as part of a comprehensive treatment strategy, especially for patients at high risk of heart failure hospitalization. Early initiation may confer cardiovascular protection and improve clinical outcomes.
Individualized assessment of comorbidities, renal function, and frailty is essential to optimize therapy and minimize adverse effects. Multidisciplinary collaboration involving cardiology, geriatrics, and pharmacy can support safe implementation.
Ongoing research and real-world data collection will help refine patient selection and monitoring protocols, potentially expanding the role of SGLT2 inhibitors in geriatric heart failure care.