Project 458305

Dementia is a major challenge for individuals, families, and the health care system. It is frustrating that effective treatment options are lacking. This necessitates the development of effective preventative strategies. Diabetes increases the risk of dementia. Different drugs for type 2 diabetes lower blood sugar via different drug actions, and these actions may benefit the brain differently. Sodium-glucose transport protein 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors are popular second-line therapies for type 2 diabetes. SGLT2 inhibitors were shown to protect against stroke, specifically hemorrhagic strokes. However, DPP4 inhibitors did not show an effect on stroke risk, but our recent study found that DPP4 use was associated with slower memory decline among people with AD dementia. The two drugs may protect the brain via different actions. Using data collected from medical records across Ontario housed at the Institute for Clinical Evaluative Sciences, we aim to determine 1) whether the use SGLT2 inhibitors and/or DPP4 inhibitors are associated with lower risk of getting dementia, and 2) whether there is a difference in dementia risk between SGLT2 inhibitor and DPP4 inhibitor use. We will use a technique called survival analysis to make these comparisons, identifying people exposed to each drug, and following them over several years. Stroke is another important factor for dementia; therefore, we will explore whether reduction in stroke risk mediates the associations between SGLT2 inhibitors and/or DPP-4 inhibitors and the risk of getting dementia. Currently, little guidance is available to help choose one drug class for diabetes over another in people who are diagnosed with or at risk for AD. The proposed studies may help take a step towards personalized AD prevention and treatment optimization, in the context of T2DM. The study will also determine which drug actions might offer the most potential to prevent dementia.