Antidiabetes Agents and Incident Depression: A Nationwide Population-Based Study

OBJECTIVE Diabetes is associated with an increased risk of depression. Some antidiabetes agents, specifically metformin and pioglitazone, have been suggested to have beneficial effects on depression, but associations between antidiabetes drugs and depression have not been systematically investigated. RESEARCH DESIGN AND METHODS We combined four Danish population-based registers to investigate whether the 20 most widely used orally administered antidiabetes drugs were associated with an altered risk of incident depression. Analyses of insulin were included for comparisons. All persons in Denmark in 2005 were included in the study and followed until 2015. Two different outcome measures of incident depression were included: 1) a diagnosis of depressive disorder at a psychiatric hospital as an inpatient or outpatient and 2) a combined measure of a diagnosis of depression or use of antidepressants. Data were analyzed using Cox regression models. RESULTS A total of 360,205 individuals using orally administered antidiabetes drugs and 64,582 using insulin at any time during the study period were included in the analyses. Continued use of metformin and combinations of drugs including metformin were associated with decreased rates of incident depression. Pioglitazone was not associated with a decreased rate of incident depression. No other antidiabetes drugs or insulin showed significant associations with depression. CONCLUSIONS Real-life population-based data suggest a positive effect of metformin on depression rates. This evidence should be used in guiding prescriptions for patients with type 2 diabetes who are at risk for developing depression, including those with prior depression or anxiety and patients with a family history of depression.