Association between diabetes and mood disorders and the potential use of anti-hyperglycemic agents as antidepressants

Epidemiological and mechanistic studies support the association between Diabetes Mellitus and mood disorders, such as Major Depressive Disorder and Bipolar Disorder. This association is especially relevant in specific domains of depressive psychopathology, such as disturbances in reward systems and cognitive functions. Several anti-hyperglycemic agents have demonstrated effects on depressive symptoms and cognitive decline and this efficacy is probably the result of an action in shared brain targets between these two groups of conditions. These medications include subcutaneous insulin, intranasal insulin, metformin, and liraglutide. The study of the mechanisms involved in the relationship between Diabetes Mellitus and mood disorders offers a new avenue of investigation, and this understanding can be applied when examining whether antidiabetic agents can be repurposed as antidepressants and mood stabilizers. The objective of this narrative review is to critically appraise the literature surrounding drugs commonly used as anti-hyperglycemic agents and their effects on the brain, while discussing their potential as a new treatment for mental illnesses, and specifically, mood disorders.