Gender difference in cardiovascular outcomes with SGLT-2 inhibitors and GLP-1 receptor agonist in type 2 diabetes: A systematic review and meta-analysis of cardio-vascular outcome trials

Background and aims: Type 2 diabetes confers a differential risk of cardiovascular (CV) disease according to the gender. Whether newly approved anti-diabetic drugs like sodium-glucose co-transport-2 inhibitors (SGLT-2Is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) that have shown a significant reduction in the CV end-points in CV outcome trials (CVOTs) also have a differential impact gender-wise, is still not clearly known. Methods: We systematically searched the medical database up to December 31, 2019 and retrieved all the dedicated CVOTs conducted with SGLT-2Is and GLP-1RAs that explicitly reported the outcome of major adverse cardiac events (MACE). Subsequently, we pooled the hazard ratio (HR) of MACE in both sexes separately and meta-analyzed the result gender-wise. Results: The meta-analysis of three CVOTs conducted with SGLT-2Is (N = 34,322), demonstrated a significant reduction in MACE in men but not in women (Men - HR, 0.90; 95% CI, 0.83 to 0.97; P = 0.006; Women - HR, 0.88; 95% CI, 0.77 to 1.00; P = 0.06) compared to placebo. The meta-analysis of seven CVOTs conducted with GLP-1RAs (N = 56,004) demonstrated a significant reduction in MACE in both sex (Men - HR, 0.88; 95% CI, 0.82 to 0.93; P < 0.0001; Women - HR, 0.88; 95% CI, 0.79 to 0.99; P = 0.03), against the placebo. Conclusions: The reduction in MACE with SGLT-2Is appears to be significantly less in women with diabetes vs men, while GLP-1RAs confers a similar reduction in MACE, irrespective of the gender. Whether these results are related to inadequate statistical power (underrepresentation of women) in CVOT, or it reflects a true gender difference, still remains to be established. (C) 2020 Diabetes India. Published by Elsevier Ltd. All rights reserved.