Abstract
BACKGROUND: Sodium-glucose cotransporter-2 (SGLT2) inhibitors, developed for type 2 diabetes mellitus (T2DM), have demonstrated cardiorenal benefits in conditions including cardiovascular (CV) disease. However, few meta-analyses have synthesized outcomes in older adults with CV disease. METHODS: A systematic review and meta-analysis of randomized controlled trials published from January 2015 to January 2025 was conducted using MEDLINE (PubMed), Embase (Ovid), and CENTRAL. We included studies that reported the risk of CV outcomes for subgroups of older adults (≥ 65 years) with CV disease. The primary outcome was a composite of hospitalization for heart failure (HHF), urgent heart failure (HF) visits, and cardiovascular death (CVD). Secondary outcomes included all-cause mortality, CVD, and HHF individually. Subgroup analyses were conducted in patients with HF, T2DM, age strata (65-74 vs. ≥ 75), SGLT2 inhibitor agent, and adverse events. RESULTS: Analyzing nine studies, SGLT2 inhibitors were associated with reducing the risk of composite outcome (HR: 0.75, 95% CI: 0.67-0.83, I (2) = 51%), all-cause mortality (HR: 0.80, 95% CI: 0.66-0.97, I (2) = 68%), CVD (HR: 0.78, 95% CI: 0.65-0.94, I (2) = 61%), and HHF (HR: 0.73, 95% CI: 0.65-0.83, I (2) = 0%). Benefits were consistent in subgroups of HF only, T2DM only, and those aged ≥ 75 years. No significant differences were observed by SGLT2 inhibitor type (p = 0.090). SGLT2 inhibitors increased the risk of genital infections (RR: 3.18, 95% CI: 2.35-4.30, I (2) = 0%) but decreased that of other serious adverse events (RR: 0.92, 95% CI: 0.86-0.97, I (2) = 64%). CONCLUSIONS: In adults aged ≥ 65 years with CV disease, SGLT2 inhibitors significantly reduce the composite risk of HHF, urgent HF visits, and CVD and secondary outcomes of all-cause mortality, CVD, and HHF, supporting their use in this population with careful monitoring of age-related risks.