Does Gender Influence the Cardiovascular Benefits Observed with Sodium Glucose Co-Transporter-2 (SGLT-2) Inhibitors? A Meta-Regression Analysis

INTRODUCTION: Although a large recent trial had shown improved cardiovascular outcomes of diabetic patients on sodium glucose co-transporter-2 (SGLT-2) inhibitors, the influence of gender differences on such outcomes is not known. Thus, we aimed to assess the impact of gender on such outcomes in the patients with type 2 diabetes mellitus receiving SGLT-2 inhibitors. METHODS: A search of electronic databases was conducted for all randomized trials comparing SGLT-2 inhibitors with placebo in patients with diabetes mellitus. Primary outcomes were all-cause mortality and cardiovascular mortality. Random effects meta-regression was conducted using the percentage of women included in the SGLT-2 inhibitor arm of each trial with a P value of <0.1 for statistical significance. RESULTS: A total of 22,256 patients from 26 trials were included. The overall odds ratio (OR) of all-cause mortality [OR = 0.72, 95% confidence interval (CI) 0.60–0.86, P < 0.001, I (2) = 0%], and cardiovascular mortality (OR = 0.67, 95% CI 0.53–0.84, P = 0.001, I (2) = 23%) were lower with SGLT-2 inhibitors. Meta-regression suggested a possible incremental increase in the OR for all-cause mortality and cardiovascular mortality as the percentage of women in the SGLT-2 inhibitor arm increased (P = 0.07 and 0.08, respectively). CONCLUSION: Gender might influence the cardiovascular benefits observed with SGLT-2 inhibitors in patients with type 2 diabetes mellitus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40119-016-0075-1) contains supplementary material, which is available to authorized users.