1308-OR: Association of Randomization to Metformin with Prevalent Cognitive Impairment Syndromes in the Diabetes Prevention Program Outcomes Study

Introduction and Objective: Whether metformin affects dementia risk is unclear. We examined the association of randomized metformin (MET) vs placebo (PBO) and Intensive Lifestyle (ILS) interventions in the Diabetes Prevention Program (DPP) with cognitive impairment (CI) in the DPP Outcomes Study (DPPOS). Methods: Participants (n=1483, mean age 74 ± 8.4) were evaluated for prevalent CI in 2022-2024. Randomization to MET, ILS or PBO (1996-1999) was followed by masked MET (1996-2002) and then open label MET in the original MET group until 2022. CI syndromes, using the National Alzheimer’s Coordinating Center Uniform Dataset version 3 forms, included (in order of severity) no CI, CI-not-Mild Cognitive Impairment (MCI), non-amnestic MCI (naMCI), amnestic MCI (aMCI), dementia. We examined the association of randomization to MET with CI syndromes using multinomial logistic regression. Results: MET exposure was 15.5 ± 7.7 person years in the MET group and after developing type 2 diabetes out-of-study MET was 4.5 ± 5.1 person years in PBO and 3.8 ± 4.8 person years in ILS groups. Randomization to MET was associated with 59-62% and 60% lower odds of dementia compared with PBO and ILS, respectively (Table). Conclusion: Long-term exposure to metformin may prevent dementia among persons with pre-diabetes and type 2 diabetes. Longer follow-up with more dementia cases is needed to confirm our finding. Disclosure P. Wander: None. L. Doherty: None. Q. Pan: None. O. Carmichael: Research Support; Current; Eli Lilly and Company. D. Dabelea: None. R.S. Turner: Research Support; Current; Lilly, Eisai Inc. Speaker's Bureau; Current; Lilly. Consultant; Current; Re:Cognition Health. S. Kuo: None. M. Munshi: Advisory Panel; Current; Abbott Diabetes. Research Support; Ended; Dexcom, Inc. A. Wallia: Research Support; Current; UnitedHealth Group. J.M. Noble: None. V. Shah: None. N. Nadkarni: None. S. Mudaliar: None. M. Temprosa: None. W. Knowler: None. J.A. Luchsinger: Consultant; Current; Merck KGaA, Novo Nordisk. Other - Merck KGaA provides investigational product including matching placebo free of charge for an NIH funded clinical trial.; Current; Merck KGaA. D. Research Group: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) (U01 DK048489), National Institute on Aging of the NIH (5 U19 AG078558).