Therefore, depressed generation of NO and PGI2 might also limit the efficacy of even potent P2Y12 antagonists despite DAPT in post-ACS patients with coexistent comorbidities, including T2DM, keeping in mind a three-way synergistic interaction between P2Y12 blockade and endothelial mediators, NO and PGI2, for adequate platelet inhibition [30–32, 71]. Here, P2RY12 is linked to type 2 diabetes mellitus.