Vinué et al. showed in atherosclerosis-prone apolipoprotein E-deficient (ApoE−/−) and insulin-resistant mice that lixisenatide can diminish the atherosclerosis burden by reducing the size of atheroma plaques, increasing plaque stability, and reprogramming macrophages to the anti-inflammatory M2 phenotype by enhanced activation of signal transducer and activator of transcription (STAT)3, which is a determinant for M2 macrophage differentiation. This evidence concerns the gene APOE and atherosclerosis.