Clinical Outcomes and Safety of SGLT2 Inhibitors in the Older Population with Heart Failure: A Systematic Review and Meta-Analysis

BACKGROUND Heart failure (HF) predominantly affects older adults, yet this group remains underrepresented in sodium-glucose cotransporter-2 inhibitor (SGLT2i) trials. Given their frailty and multimorbidity, clarifying the potential benefit and safety of SGLT2i in older HF patients is essential. METHODS PubMed, ScienceDirect, and Cochrane Central were searched through August 2025 for randomized controlled trials (RCTs) and observational studies comparing SGLT2i with control in patients aged ≥65 years with HF. Hazard ratios (HRs), risk ratios (RRs), and mean differences (MDs) were pooled using random-effects models. RESULTS Ten studies (4 RCTs, 6 cohorts; n = 20,844) were included. SGLT2i was associated with a lower hazard of all-cause mortality (HR 0.81 [95% CI 0.72-0.90]; p < 0.001), cardiovascular (CV) death (HR 0.83 [0.74-0.94]; p = 0.004), first HF hospitalization (HR 0.73 [0.66-0.80]; p < 0.001), composite CV death or HF hospitalization (HR 0.78 [0.70-0.87]; p < 0.001), and rehospitalization (HR 0.60 [0.53-0.69]; p < 0.001). SGLT2i lowered serious adverse events (RR 0.92 [0.89-0.95]; p < 0.001) and slowed renal function decline (MD 1.86 [1.15-2.58] mL/min/1.73 m² per year; p < 0.001). An increase was observed in genital (RR 3.07 [2.03-4.64]; p < 0.001) and urinary tract infections (RR 1.19 [1.03-1.38]; p = 0.02). CONCLUSIONS In older patients with HF, SGLT2i was associated with lower mortality and HF hospitalizations and with a slower renal decline, while largely maintaining a favorable safety profile. These findings support the consideration of SGLT2i as an important therapeutic option for older adults with HF.