In T2DM patients with obesity, GLP-1 RAs significantly reduced the risk of MACE versus placebo (relative risk, RR [95% confidence interval, CI]: 0.88 [0.81–0.96]), whereas SGLT-2 inhibitors showed a tendency (RR [95% CI]: 0.91 [0.83–1.00]). This evidence concerns the gene GCG and obesity due to melanocortin 4 receptor deficiency.