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

Abstract

Objective: Diabetes is a risk factor for dementia, but whether antidiabet ic medication decreases the risk is unclear. We examined the association between antidiabetic medication and de mentia. 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 contr ols 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 inh ibitors 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), respect ively), with a gradual decrease in odds of dementia for each increase in daily defined dose. Analyses of the most freque nt treatment regimes did not show any synergistic effects of combined treatment. Conclusion: Use of metformin, DPP4 inhibitors, GLP1 analogs and SGLT2 inhi bitors was associated with lower risk of dementia in patients with diabetes.