Efficacy of SGLT-2 inhibitors in older adults with diabetes: Systematic review with meta-analysis of cardiovascular outcome trials

Aims: Sodium–glucose cotransporter-2 inhibitors (gliflozins) and statins are oral drugs that may have beneficial cardiovascular effects in patients with type 2 diabetes, especially in those with known cardiovascular disease. We planned a systematic review and meta-analysis of cardiovascular outcome trials (CVOTs) that evaluated the effect of gliflozins on MACE risk in patients with T2D stratified by age and by statin use. Methods: The electronic search was carried out until 20 January 2020. RCTs were included if they were CVOTs performed in adults with T2D, compared add-on therapy with any gliflozin versus placebo, and had major cardiovascular events (MACE) as primary outcome. We limited the evaluation to MACE in order to minimize the statistical impact of post-hoc analyses. We used a random-effect model to calculate hazard ratio (HR) and 95% CI. Results: The hazard ratio for MACE was 0.95 (95% CI, 0.86–1.05) in people <65 years and 0.83 (95% CI, 0.71–0.96) for people ≥65 years, with no subgroup differences (P-value = 0.15), suggesting that the effect was consistent across age categories. The hazard ratio for MACE was 0.87 (95% CI, 0.81–0.94) in people taking a statin and 0.88 (95% CI, 0.77–1.01) for people not taking statin, with no subgroup differences (P-value = 0.90). Conclusions: The results are reassuring, as they confirm that the efficacy profile of gliflozins is unchanged by age, and may further enhance the CV protection offered by statin.