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