Comparative Effect of Metformin versus Sulfonylureas with Dementia and Parkinson's Disease Risk in US patients over 50 with Type 2 Diabetes Mellitus
Abstract
Introduction: Type 2 diabetes is a risk factor for dementia and Parkinson's disease (PD). Drug treatments for diabetes, such as metformin, could be used as potential novel treatments for these neurological conditions. Using medical records from the USA (OPTUM) we aimed to assess the association of metformin with all cause dementia, dementia subtypes, and PD compared to sulfonylureas. Research Design and Methods: A new user comparator study design was conducted in patients >50 years old with diabetes who were new users of metformin or sulfonylureas between 2006-2018. Primary outcomes were all cause dementia and PD. Secondary outcomes were Alzheimer's disease (AD), vascular dementia (VD), and mild cognitive impairment (MCI). Cox proportional hazard models with inverse probability of treatment weighting (IPTW) were used to estimate the hazard ratios (HR). Sub analyses included stratification by age, race, renal function, and glycemic control. Results: We identified 96,140 and 16,451 new users of metformin and sulfonylureas, respectively. Mean age was 66.4 +/- 8.2 years (48% male, 83% Caucasian). Over the 5-year follow-up, 3,207 patients developed all cause dementia (2,256 [2.3%] metformin, 951 [5.8%] sulfonylurea users) and 760 patients developed PD (625 [0.7%] metformin, 135 [0.8%] sulfonylurea users). After IPTW, HRs for all cause dementia and PD were 0.80 (95%CI 0.73-0.88) and 1.00 (95%CI 0.79-1.27). HRs for AD, VD and MCI were 0.81 (0.70-0.94), 0.79 (0.63-0.99) and 0.91…
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