Comparing the Efficacy of Sodium–Glucose Cotransporter 2 Inhibitors Among Nonolder and Older Patients: A Systematic Review and Meta-Analysis

ABSTRACT: Large scale randomized trials have shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors can reduce cardiovascular events in patients with cardiovascular disease or with increased risks of cardiovascular disease. However, the evidence from older patients is limited. To compare the efficacy of SGLT2 inhibitors among nonolder and older patients, we have searched PubMed, Cochrane Central, and Embase until February 2023 for randomized controlled trials investigating SGLT2 inhibitors in older (age ≥65 years) patients with diabetes mellitus, chronic kidney disease, and chronic heart failure. The primary outcome was a composite outcome of cardiovascular death, acute myocardial infarction, and stroke. The secondary outcomes were exacerbation of heart failure, kidney disease progression, and a composite of cardiovascular death and heart failure. Our search identified 11 randomized controlled trials with a total of 79,370 patients. SGLT2 inhibitors were associated with a reduced risk of the primary outcome in the total cohort [hazard ratio (HR): 0.91; confidence intervals (CI), 0.84-0.99] with concordant results in both nonolder and older populations (HR: 0.96; CI, 0.88-1.05, HR: 0.87; CI, 0.75-1.01, respectively) without subgroup differences ( P = 0.23), and a reduced risk of developing the composite of cardiovascular death and heart failure exacerbation in both nonolder and older populations (HR: 0.77; CI, 0.67-0.87, HR: 0.76; CI, 0.71-0.82, respectively) without subgroup differences ( P = 0.96). A meta-analysis could not be performed for the other outcomes. These results suggested that SGLT2 inhibitors were similarly associated with reduced risks of cardiovascular events across the spectrum of nonolder and older patients with risk factors for developing cardiovascular disease.