Cardiovascular outcomes of SGLT-2 inhibitors and GLP-1 agonist based on race, ethnicity, and gender: A systematic review and meta-analysis of randomized trials

Abstract

The ethnic differences in cardiovascular outcomes with sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes and heart failure are not well established. We conducted the current study to evaluate the effects of both drugs on the major adverse cardiovascular effects (MACE) stratified by race, ethnicity, and gender. We searched Medline (via PubMed), Embase, and the Cochrane Library for randomized controlled trials (RCTs) investigating the effects of SGLT2 inhibitors and GLP-1 receptor agonists on the MACE risk. The data of MACE were pooled as risk ratios (RRs), with 95% confidence intervals, using R software (meta-package 4.9-0) for windows and a subgroup analysis was conducted. Sixteen RCTs were finally included in the meta-analysis. In patients with T2DM and high cardiovascular risk, the effect showed that SGLT-2 inhibitors and GLP-1 receptor agonists significantly reduced the MACE risk among the White and Asian populations, and both males and females. Subgroup analysis showed no significant differences between SGLT2 inhibitors and GLP-1 receptor agonists on the MACE outcomes stratified by race, ethnicity, or gender. In patients with known heart failure, the effect showed that SGLT-2 inhibitors significantly reduced MACE risk in all subgroups. It remains unclear whether the lack of significant reduction in MACE risk and significant heterogenicity observed could be because of inconsistent representation of these ethnic groups across RCTs. Further multicenter RCTs with a larger sample size are recommended to evaluate the effect of these drugs to better understand the ethnic difference in cardiovascular outcomes.