Antidiabetic medication and risk of dementia in patients with type 2 diabetes. A nested case-control study.

Objective: 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. Design: 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 and 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 calender 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 (DPP4) inhibitors, glucagonlike peptide 1 (GLP1) analogs, sodium-glucose transport protein 2 (SGLT2) inhibitors and acarbose). Methods: 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, DPP4 inhibitors, GLP1 analogs, and SGLT2 inhibitors were associated with lower odds of dementia after multible adjustments (ORs of 0.94 (95% confidence interval (CI): 0.89-0.99), 0.80 (95% CI 0.74-0.88), 0.58 (95% CI: 0.50-0.67), and 0.58 (95% CI: 0.42-0.81), respectively), with a gradual decrease in odds of dementia for each increase in daily defined dose. Analyses of the most frequent treatment regimes did not show any synergistic effects of combined treatment. Conclusion: Use of metformin, DPP4 inhibitors, GLP1 analogs and SGLT2 inhibitors was associated with lower risk of dementia in patients with diabetes.