Safety and Efficacy of Sodium-Glucose Cotransporter 2 Inhibitors in Older Adults with Variable Disease States: A Meta-analysis of Large Placebo-Controlled Trials

Abstract

Background: Recent guidelines recommend the use of sodium-glucose cotransporter 2 (SGLT-2) inhibitors (SGLT2i) in patients suffering from cardiorenal diseases. However, the safety and efficacy of SGLT2i in older adults with atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and chronic kidney disease (CKD) remain unclear. Methods: Online databases were queried from inception to 11 July 2023 to identify primary or secondary analyses for inclusion. Efficacy outcomes included all-cause mortality, cardiovascular (CV) death, hospitalization for heart failure (HHF), major adverse cardiac events (MACE), CV death/HHF composite, and cardiorenal composite events. Safety endpoints included acute kidney injury (AKI), serious adverse events, genital infections, limb amputation, fractures, urinary tract infections (UTI), and volume depletion. Data were pooled using a random-effects model to derive risk ratios (RRs) and 95% confidence intervals (CIs). Results: Eight trials with 32,541 older adults identified in primary or secondary analyses were included. In older adults, SGLT2i reduced the risk of all-cause mortality (RR 0.88; 95% CI 0.83– 0.95), CV death (RR 0.82; 95% CI 0.74–0.92), HHF (RR 0.72; 95% CI 0.66–0.79), MACE (RR 0.87; 95% CI 0.77–0.99), CV death/HHF composite (RR 0.78; 95% CI 0.70–0.88), and cardiorenal composite events (RR 0.77; 95% CI 0.70–0.85). For safety endpoints, SGLT2i decreased the risk of serious adverse events (RR 0.92; 95% CI 0.89–0.95) and increased the risk of genital infections (RR 3.48; 95% CI 2.58–4.69). Conclusions: This analysis of randomized trials demonstrates that SGLT2i are efficacious in older adults. However, since older individuals are often underrepresented in most clinical trials, further research targeting this growing demographic is essential.