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

Abstract

Background and aims: Both type 2 diabetes and cardiovascular (CV) disease develops at a younger age in Asians and often have a higher risk of mortality. Both sodium-glucose co-transport-2 inhibitors (SGLT-2Is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown a significant reduction in CV end-points in CV outcome trials (CVOTs). Whether similar CV benefit exists in Asians, is not yet clearly known.

Methods: We systematically searched relevant medical database up to January 31, 2020 and retrieved all the dedicated CVOTs conducted with SGLT-2Is and GLP-1RAs. Subsequently, we meta-analyzed the pooled data of hazard ratio (HR) of major adverse cardiac events (MACE) in Asians. We additionally analyzed the data of heart failure hospitalization (HHF) or CV-death with SGLT-2Is in Asians.

Results: The meta-analysis of three CVOTs conducted with SGLT-2Is (N = 4987), did not find any significant reduction in MACE (HR, 0.88; 95% CI, 0.67 to 1.15; P = 0.35) and HHF or CV-death (HR, 0.86; 95% CI, 0.55 to 1.36; P = 0.53) in Asians, compared to the placebo. In contrast, the meta-analysis of seven CVOTs conducted with GLP-1RAs (N = 4298) demonstrated a significant reduction in MACE, compared to the placebo (HR, 0.71; 95% CI, 0.59 to 0.86; P < 0.0001).

Conclusions: This meta-analysis found a significant reduction in MACE with GLP-1RAs but not with SGLT-2Is in Asians. No significant reduction in HHF or CV-death demonstrated either with SGLT-2Is in Asians. Whether these results are related to an inadequate statistical power, or due to underrepresentation of Asians, or a true ethnic difference, remains to be established.

Keywords: Asians; Cardio-vascular outcome trials; Ethnicity; GLP-1 receptor agonists; SGLT-2 inhibitors.