Metformin, Other Antidiabetic Drugs, and Risk of Alzheimer's Disease: A Population‐Based Case–Control Study

Objectives To explore the risk of developing Alzheimer's disease (AD) in individuals with diabetes mellitus treated with metformin or other antidiabetic drugs. Design Case–control study. Setting The United Kingdom–based General Practice Research Database (GPRD), a well‐established primary care database. Participants Seven thousand eighty‐six individuals aged 65 and older with an incident diagnosis of AD identified between 1998 and 2008 and the same number of matched controls without dementia. Matching criteria were age, sex, general practice, calendar time, and years of history in the database. Measurements Comparison of previous use of metformin or other antidiabetic drugs between cases and controls and calculation of corresponding odds ratios (ORs) with 95% confidence intervals (CIs), using conditional logistic regression. Risk estimates were stratified according to duration of use and adjusted for potential confounders. Results As compared with nonusers, long‐term users of 60 or more metformin prescriptions were at greater risk of developing AD (adjusted OR (AOR) = 1.71, 95% CI = 1.12–2.60), but there was no consistent trend with increasing number of prescriptions. Long‐term use of other antidiabetic drugs such as sulfonylureas (AOR = 1.01, 95% CI = 0.72–1.42), thiazolidinediones (AOR = 0.87, 95% CI = 0.31–2.40), or insulin (AOR = 1.01, 95% CI = 0.58–1.73) was not related to an altered risk of developing AD. Conclusion Long‐term use of sulfonylureas, thiazolidinediones, or insulin was not associated with an altered risk of developing AD. There was a suggestion of a slightly higher risk of AD in long‐term users of metformin.