Randomized metformin and cognitive outcomes in the Diabetes Prevention Program Outcomes Study
Abstract
ABSTRACT:
Importance: Metformin may influence risk of dementia, with prior conflicting observations of protection or harm.
Objective: To determine the association of randomization to metformin vs. placebo or intensive lifestyle intervention (ILS) in the Diabetes Prevention Program (DPP) with cognitive outcomes (cognitive impairment syndromes and trajectories of cognitive test performance) during the DPP Outcomes Study (DPPOS).
Design, Setting & Participants: Prospective long-term follow-up of DPP/DPPOS participants at 27 U.S. centers among adults who were at high risk for type 2 diabetes (T2D) at baseline.
Exposures: Randomization to metformin, placebo, or ILS (1996–1999) for 3.2 years followed by open-label metformin in the original randomized metformin group until 2021.
Main Outcomes & Measures: Cognitive impairment syndromes were adjudicated in 2022– 2024 in 1,483 participants (median age 74 [IQR 68, 80]) using the National Alzheimer’s Coordinating Center Uniform Dataset version 3. Cognitive performance in executive and memory domains was ascertained with repeated cognitive tests between 2009 and 2024. Multinomial logistic regression and mixed-effects models were fit to examine associations of randomization to metformin with cognitive outcomes.
Results: Total metformin exposure (mean ± SD) was 15.5 ±7.7 years/person in the metformin group. Persons in the placebo and ILS groups received out-of-study metformin usually after developing diabetes with mean metformin total…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 1,483 participants or records.
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