In this large nationwide cohort study of 1 022 728 type 2 diabetes patients treated with one of three antidiabetic medications, we found that, compared with DPP‐4 inhibitors, (1) initiating treatment with low‐affinity cardiac mitoKATP channel sulfonylureas was not associated with an increased MACE risk; however, (2) starting therapy with high‐affinity cardiac mitoKATP channel sulfonylureas was associated with a 1.23‐fold increased MACE risk. This evidence concerns the gene DPP4 and type 2 diabetes mellitus.