<i>GRIN1</i> encodes NMDARs and has been associated with depression and T2D; however, its role in the coexistence of MDD and T2D and the treatment response to antidepressants has yet to be explored.<h4>Objective</h4>We aimed to evaluate the association between <i>GRIN1</i> rs28489906 and MDD and treatment response to antidepressants in patients with T2D.<h4>Methods</h4>A prospective study was conducted on T2D patients enrolled in a comprehensive care program with follow-up at 3 months. Here, GRIN1 is linked to depressive disorder.