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Cited by 75Dementia and Cognitive Impairment ResearchDiabetes Treatment and ManagementMetabolism, Diabetes, and Cancer

Metformin, lifestyle intervention, and cognition in the Diabetes Prevention Program Outcomes Study

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Luchsinger, José A., Ma, Yong, Christophi, Costas A., Florez, Hermes, Golden, Sherita H., Hazuda, Helen, Crandall, Jill, Venditti, Elizabeth +4 more·2017·Diabetes Care
DOI 10.2337/dc16-2376PMC PMC5481986
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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.

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  • Studies examining the effects of diabetes prevention or intensive glycemic and blood pressure management to achieve specific goals have not demonstrated a reduction in brain function decline.

    “However, studies examining the effects of diabetes prevention or intensive glycemic and blood pressure management to achieve specific goals have not demonstrated a reduction in brain function decline (18,19).”

    From 13. Older Adults: <i>Standards of Care in Diabetes—2024</i> (2024) · cites this paper as [19]

    The Conclusions (page unavailable) report no difference in cognitive performance between diabetes-prevention intervention arms about 12 years after randomization. They also report that an intensive glycemic-control arm in ACCORD-MIND showed no cognitive benefit. The paper does not establish the claim about intensive blood-pressure management, and because it collected no baseline cognitive data, its own finding concerns later cognitive performance rather than a measured reduction in cognitive decline. (LLM, conf=0.86)

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  • Studies on diabetes prevention or intensive glycemic and blood pressure management have not demonstrated a reduction in cognitive decline.

    “However, studies on diabetes prevention or intensive glycemic and blood pressure management have not demonstrated a reduction in cognitive decline (20,21).”

    From 13. Older Adults: Standards of Care in Diabetes—2025 (2025) · cites this paper as [21]

  • Studies on diabetes prevention or intensive glycemic and blood pressure management have not demonstrated a reduction in cognitive decline.

    “However, studies on diabetes prevention or intensive glycemic and blood pressure management have not demonstrated a reduction in cognitive decline (25,26).”

    From 13. Older Adults: Standards of Care in Diabetes—2026 (2026) · cites this paper as [26]

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Research works printed but not linked: 24

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Authors
Luchsinger, J. A., Ma, Y., Christophi, C. A., Florez, H., Golden, S. H., Hazuda, H., Crandall, J., Venditti, E., Watson, K., Jeffries, S., Manly, J. J., & Pi-Sunyer, F. X.
Affiliations
  • Columbia University Medical Center, New York, NY
  • George Washington University (US)
  • University of Miami (US)
  • Johns Hopkins University (US)
  • The University of Texas at San Antonio Health Science Center (US)
  • Albert Einstein College of Medicine (US)
  • University of Pittsburgh (US)
  • University of California, Los Angeles (US)
  • Columbia University Irving Medical Center (US)
ORCID
Venue
Diabetes Care
Publisher
American Diabetes Association
Published
2017-06-13
Volume
40
Issue
7
Pages
958-965
ISSN
  • 0149-5992 (ISSN-L)
  • 1935-5548
DOI
10.2337/dc16-2376
PMC
PMC5481986
OpenAlex
W2612859522
Cited by
75
References
8
Citations by year
2026: 3 · 2025: 11 · 2024: 6 · 2023: 9 · 2022: 9 · 2021: 11 · 2020: 10 · 2019: 9 · 2018: 2 · 2017: 4 · 2016: 1
FWCI
5.62
Type
journal article
Language
en
Open access
Licence
www.diabetesjournals.org/content/license (vor, 8 d)
Locations
  • Diabetes Care (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Diabetes and Digestive and Kidney Diseases (U01 DK048489)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords
metformin, lifestyle intervention, cognition, type 2 diabetes prevention, HbA1c, glycemia, cognitive safety, Diabetes Prevention Program Outcomes Study, APOE ε4
MeSH terms
Aged, Blood Glucose, Cholesterol, Cognition, Diabetes Mellitus, Type 2, Ethnicity, Female, Follow-Up Studies, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Life Style, Male, Metformin, Middle Aged, Triglycerides, Treatment Outcome, Polymorphism, Single Nucleotide

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