Metformin, Lifestyle Intervention, and Cognition in the Diabetes Prevention Program Outcomes Study

José A Luchsinger, Yong Ma, Costas A Christophi, Hermes Florez, Sherita H Golden, Helen Hazuda, Jill Crandall, Elizabeth Venditti, Karol Watson, Susan Jeffries, Jennifer J Manly, F Xavier Pi-Sunyer, Diabetes Prevention Program Research Group, José A Luchsinger, Yong Ma, Costas A Christophi, Hermes Florez, Sherita H Golden, Helen Hazuda, Jill Crandall, Elizabeth Venditti, Karol Watson, Susan Jeffries, Jennifer J Manly, F Xavier Pi-Sunyer, Diabetes Prevention Program Research Group

Abstract

Objective: We examined the association of the Diabetes Prevention Program (DPP) intervention arms (lifestyle intervention, metformin, and placebo) with cognition in the Diabetes Prevention Program Outcomes Study (DPPOS). We also examined metformin use, incident type 2 diabetes, and glycemia as exposures.

Research design and methods: The DPP lasted 2.8 years, followed by a 13-month bridge to DPPOS. Cognition was assessed in DPPOS years 8 and 10 (12 and 14 years after randomization) with the Spanish English Verbal Learning Test (SEVLT), letter fluency and animal fluency tests, Digit Symbol Substitution Test (DSST), and a composite cognitive score.

Results: A total of 2,280 participants (749 lifestyle, 776 metformin, and 755 placebo) aged 63.1 ± 10.7 years underwent cognitive assessments; 67.7% women, 54.6% non-Hispanic white, 20.7% non-Hispanic black, 14.6% Hispanic, 5.5% American Indian, and 4.6% Asian; 26.6% were homozygous or heterozygous for APOE-ε4. At the time of cognitive assessment, type 2 diabetes was higher in the placebo group (57.9%; P < 0.001) compared with lifestyle (47.0%) and metformin (50.4%). Metformin exposure was higher in the metformin group (8.72 years; P < 0.001) compared with placebo (1.43 years) and lifestyle (0.96 years). There were no differences in cognition across intervention arms. Type 2 diabetes was not related to cognition, but higher glycated hemoglobin at year 8 was related to worse cognition after confounder adjustment. Cumulative metformin exposure was not related to cognition.

Conclusions: Exposure to intensive lifestyle intervention or metformin was not related to cognition among DPPOS participants. Higher glycemia was related to worse cognitive performance. Metformin seemed cognitively safe among DPPOS participants.

Trial registration: ClinicalTrials.gov NCT00004992 NCT00038727.

© 2017 by the American Diabetes Association.

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Source: PubMed

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