Do GLP-1RAs and SGLT-2is reduce cardiovascular events in black patients with type 2 diabetes? A systematic review and meta-analysis

Aims While recent cardiovascular safety trials (CVST) concerning newer diabetes medications included mostly white participants, results are being generalized to all races in recent guidelines. This raises a controversial question regarding the appropriateness of applying CVST data to black patients with type 2 diabetes. Materials and methods We searched for randomized trials comparing diabetes medications to placebo in type 2 diabetes and investigated three- or four-point major adverse cardiovascular events (MACE). Data concerning black patients were then extracted. As the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) updated their recommendations for patients with established cardiovascular risk based on the CVST showing cardiovascular benefit, we performed a sensitivity analysis by including those trials only. Results A total of 11 trials were included, investigating a glucagon-like peptide-1 receptor agonist (GLP-1RA) in five, a sodium-glucose co-transporter-2 inhibitor (SGLT-2i) in two and dipeptidyl peptidase-4 inhibitors (DPP-4i) in four. Of the 102 416 participants enrolled in the included trials, only 4601 were black (4.5%). Pooled results showed no significant difference in the incidence of MACE among diabetes medications (GLP-1RA, SGLT-2i or DPP-4i) and placebo in black patients with type 2 diabetes (relative risk [RR] [95% CI], 0.94 [0.77,1.16]). Restricting the analysis to different classes of diabetes medication, the results remained non-significant. Restricting the analysis to CVST with significant outcomes, the results remained non-significant (RR [95% CI], 0.97 [0.68,1.39]). Conclusions Given that black patients with type 2 diabetes were not well represented in CVSTs and such trials were underpowered to evaluate racial differences, it remains unclear whether GLP-1RAs or SGLT-2is would reduce cardiovascular risk in such patients, and additional studies targeting black patients are urgently needed.