Efficacy of sodium-glucose cotransporter 2 inhibitors on cardiorenal outcomes in older patients: a systematic review and meta-analysis

Abstract Background Recent randomized controlled trials (RCTs) showed that sodium-glucose cotransporter 2 (SGLT2) inhibitors improve cardiorenal outcomes in patients with increased risks of cardiovascular diseases. However, only limited data from subgroup analyses are available for older patients. Methods A systematic review was performed by searching PubMed, Cochran Central, and Embase through February 2023 for RCTs of SGLT2 inhibitors that were performed in adults and large (≥500 participants per group). Hazard ratios (HRs) and relative risk estimates in older subgroups ≥ 65 years were extracted from each study and were pooled using a random-effects meta-analysis. The primary outcome was a composite of cardiovascular death, myocardial infarction, or stroke. The secondary outcomes were heart failure exacerbation, adverse renal outcomes, and a composite outcome of cardiovascular death or heart failure exacerbation. Results This study included 10 RCTs. SGLT2 inhibitors decreased the primary outcome but it did not reach statistical significance in older subgroups (HR, 0.86; 95% CI, 0.73-0.1.00, p = 0.06). Whereas SGLT2 inhibitors were associated with decreased risks of heart failure exacerbation (HR, 0.76; 95% CI, 0.67-0.87), adverse renal outcome (HR, 0.58; 95% CI, 0.43-0.77), and a composite outcome of cardiovascular death or heart failure exacerbation (HR, 0.76; 95% CI, 0.70-0.83). Conclusions SGLT2 inhibitors were associated with improved cardiovascular outcomes in older patients. Further therapeutic data and sufficient long-term safety data are warranted in this population.