The comorbidity of mental and physical illnesses is on the rise, particularly with the co-occurrence of major depression (MD) and type 2 diabetes mellitus (T2DM). Patients with DM exhibit a significantly elevated risk for MD, with the interplay of inflammatory responses, activation of the hypothalamic-pituitary-adrenal axis, oxidative stress, and abnormalities within the kynurenine pathway contributing to the pathophysiology of both diseases. Inflammatory cytokines and vascular endothelial growth factor abnormalities have emerged as critical factors common to MD and T2DM. Effective pharmacological treatments such as selective serotonin reuptake inhibitors and cognitive-behavioral therapy (CBT) are available, with CBT demonstrating particularly beneficial effects on medication adherence and glycemic control. This review aims to elucidate the complex interplay between MD and T2DM, highlighting the shared mechanisms of pathophysiology and their therapeutic implications, ultimately informing clinical practice for better management of comorbid conditions.
