Background: Diabetes is a risk factor for dementia, but whether antidiabetic medication decreases the risk is unclear. We examined the association between antidiabetic medication and dementia.

Methods: We performed a nested case-control study within a cohort of all 176,250 patients registered with type 2 diabetes in the Danish National Diabetes Register between 1995-2012. This population was followed for dementia diagnosis or anti-dementia medication use until May 2018. Using risk-set sampling, each dementia case (n=11,619) was matched on follow-up time and calendar year of dementia with four controls randomly selected among cohort members without dementia (n=46,476). Ever use and mean daily defined dose of antidiabetic medication was categorized in types (insulin, metformin, sulfonylurea and glinides combined, glitazone, dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide 1 (GLP-1) analogs, sodium-glucose transport protein 2 (SGLT2) inhibitors and acarbose). Conditional logistic regression models were fitted to calculate odds ratios (ORs) for dementia associated with antidiabetic medication use, adjusting for potential confounders.

Results: Use of metformin, DPP-4 inhibitors, GLP-1 analogs, and SGLT2 inhibitors were associated with lower odds of dementia after multiple adjustments (ORs of 0.90 (95% confidence interval (CI) 0.86-0.96), 0.80 (95% CI 0.73-0.88), 0.53 (95% CI 0.38-0.74), and 0.53 (95% CI 0.38-0.74), respectively), with a gradual decrease in odds of dementia for each increase in daily defined dose. Analyses of the most frequent treatment regimens did not show any synergistic effects of combined treatment.

Conclusion: Use of metformin, DPP-4 inhibitors, GLP-1 analogs and SGLT2 inhibitors were associated with lower risk of dementia in patients with type 2 diabetes. If confirmed in future studies these antidiabetics should be considered in interventions to prevent dementia.


I. Wium-Andersen: None. M. Osler: None. M. Jørgensen: None. J. Rungby: None. M. Wium-Andersen: None.


Jaschafonden; Lundbeck Foundation; Danish Medical Association; Danish Diabetes Association; M.D. Gerhard Linds Grant; Lundbeck Foundation/Novo Nordisk Foundation; Family Hede Nielsen Foundation; Holger Rabitz and Wife Doris Mary, born Phillip’s Memorial Foundation

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at