Comprehensive evaluation of cardiovascular efficacy and safety outcomes of SGLT2 inhibitors in high risk patients of cardiovascular disease: systematic review and meta-analysis

Abstract

Supplemental Digital Content is available in the text. Objectives To demonstrate a magnitude of the cardiovascular benefits, concomitantly analyzing the safety outcomes of sodium-glucose cotransporter 2 inhibitor (SGLT2-I) comprehensively, as a class effect in a larger sample size combined from recent randomized control trials. Methods We searched electronic databases using specific terms and evaluated 6 efficacy and 10 safety outcomes. Odds ratios (ORs) and 95% confidence interval (CI) were used to compare two interventions. Results Five studies (n\u2009=\u200941\u2009267) were included, among which 23\u2009539 received SGLT2-I. The SGLT2-I group favored reduction in major adverse cardiovascular events (OR, 0.78; 95% CI, 0.62–0.98; P\u2009=\u20090.03), cardiovascular death (CVD) or heart failure hospitalization (OR, 0.60; 95% CI, 0.46–0.80; P\u2009=\u20090.0004), rate of hospitalization for heart failure (OR, 0.56; 95% CI, 0.44–0.72; P\u2009<\u20090.00001), CVD (OR, 0.68; 95% CI, 0.50–0.93; P\u2009=\u20090.01), all-cause mortality (OR, 0.67; 95% CI, 0.48–0.93; P\u2009=\u20090.02) and myocardial infarction (OR, 0.79; 95% CI, 0.64–0.99; P\u2009=\u20090.04) when compared to the placebo group. Safety analysis showed higher diabetic ketoacidosis (DKA) rate in SGLT2-I group (OR, 2.33; 95% CI, 1.40–3.90; P\u2009=\u20090.001); in contrast, major hypoglycemic events were significantly lower (OR, 0.79; 95% CI, 0.73–0.87; P\u2009<\u20090.00001). AKI was significantly higher in the placebo group (OR, 0.76; 95% CI, 0.65–0.88; P\u2009=\u20090.0004). There were no statistically significant effects on other outcomes. Conclusion In selected high-risk patients of cardiovascular disease, the SGLT2-I is a potential effective class of drugs for improving cardiovascular outcomes and all-cause mortality without an increased risk of all other major complications except DKA on this meta-analysis.