This analysis showed that GLP-1 RAs significantly reduced the risk of MACE versus placebo in participants with T2DM who did or did not have obesity (RR 0.88 [0.82–0.95] and 0.88 [0.79–0.98], respectively), whereas SGLT-2 inhibitors did not (RR 0.94 [0.85–1.03] and 0.91 [0.80–1.04], respectively). This evidence concerns the gene GLP1R and obesity due to melanocortin 4 receptor deficiency.