Association of metformin and depression in patients with type 2 diabetes

Emerging evidence showed metformin may have pleiotropic effects on ameliorating depression. However, whether metformin was associated with decreased risk of depression remains unclear.A historical cohort study was conducted based on a medical claim database from 2010 to 2017 in Beijing, China. Patients newly diagnosed with T2D were classified into the metformin and non-metformin groups according to their initial antidiabetic prescription. The incidences of depression between the groups were compared using Cox proportional regression model.There were 193,624 (37.4 %) and 323,930 (62.6 %) T2D patients in the metformin and non-metformin groups. The mean age was 54.9 (SD: 13.1) years and 53.9% were females. With a median follow-up of 3.2 years, 64,963 patients developed depression. The adjusted incidence of depression in the metformin group (30.6, 95 % CI: 30.1, 31.0 per 1000 person-years) was significantly lower than in the non-metformin group (39.6, 95 % CI: 39.3, 40.0 per 1000 person-years, P 0.001). The metformin group was significantly associated with a lower risk of depression compared with the overall non-metformin group (HR: 0.77, 95% CI: 0.75, 0.78), as well as compared with α-glucosidase inhibitors (HR: 0.73, 95 % CI: 0.71, 0.74), sulfonylureas (HR: 0.84, 95 % CI: 0.82, 0.86), and glinides (HR: 0.85, 95 % CI: 0.82, 0.88), except for thiazolidinediones (HR: 0.96, 95 % CI: 0.91, 1.01). The association between metformin and lower depression risk was significant in all the age and sex subgroups.Metformin was associated with a lower risk of depression compared with other oral hypoglycemic agents, indicating a potential pleiotropic effect on depression.