Metformin and Risk of Alzheimer's Disease Among Community-Dwelling People With Diabetes: A National Case-Control Study.

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  • Additional Information
    • Source:
      Publisher: Oxford University Press Country of Publication: United States NLM ID: 0375362 Publication Model: Print Cited Medium: Internet ISSN: 1945-7197 (Electronic) Linking ISSN: 0021972X NLM ISO Abbreviation: J Clin Endocrinol Metab Subsets: MEDLINE
    • Publication Information:
      Publication: 2017- : New York : Oxford University Press
      Original Publication: Springfield, Ill. : Charles C. Thomas
    • Subject Terms:
      Alzheimer Disease/*epidemiology ; Biomarkers/*analysis ; Diabetes Mellitus, Type 2/*drug therapy ; Hypoglycemic Agents/*adverse effects ; Metformin/*adverse effects; Age Factors ; Aged ; Aged, 80 and over ; Alzheimer Disease/chemically induced ; Alzheimer Disease/pathology ; Blood Glucose/analysis ; Case-Control Studies ; Female ; Finland/epidemiology ; Follow-Up Studies ; Humans ; Independent Living ; Male ; Prognosis ; Registries ; Risk Factors
    • Abstract:
      Context: Type 2 diabetes has been linked with an increased risk of Alzheimer's disease (AD). Studies on the association between metformin use and AD have reported conflicting results.
      Objective: To investigate whether metformin use modifies the association between diabetes and incident, clinically verified AD.
      Design: Nested case-control study.
      Setting: All community-dwelling people in Finland.
      Participants: Cases were all community-dwelling Finns with AD diagnosed from 2005 to 2011 and with diabetes diagnosed ≥ 3 years before AD (n = 9862). Cases were matched with up to 2 control persons by age, sex, and diabetes duration (n = 19 550).
      Main Outcome Measure: Cumulative metformin exposure was determined from reimbursed dispensings over a 10- to 16-year period. Adjusted odds ratios (aORs) were calculated using conditional logistic regression to estimate associations, with adjustment for potential confounders.
      Results: A total of 7225 (73.3%) cases and 14528 (74.3%) controls received metformin at least once. Metformin use (ever use) was not associated with incident AD (aOR 0.99; 95% confidence interval [CI], 0.94-1.05). The adjusted odds of AD were lower among people dispensed metformin for ≥ 10 years (aOR 0.85; 95% CI, 0.76-0.95), those dispensed cumulative defined daily doses (DDDs) of < 1825-3650 (aOR 0.91; 95% CI, 0.84-0.98) and > 3650 DDDs (aOR 0.77; 95% CI, 0.67-0.88), and among persons dispensed an average of 2 g metformin daily (aOR 0.89; 95% CI, 0.82-0.96).
      Conclusion: In this large national sample we found no evidence that metformin use increases the risk of AD. Conversely, long-term and high-dose metformin use was associated with a lower risk of incident AD in older people with diabetes.
      (© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: [email protected].)
    • Contributed Indexing:
      Keywords: Alzheimer’s disease; Finland; biguanide; dementia; diabetes; metformin
    • Accession Number:
      0 (Biomarkers)
      0 (Blood Glucose)
      0 (Hypoglycemic Agents)
      9100L32L2N (Metformin)
    • Publication Date:
      Date Created: 20191129 Date Completed: 20210104 Latest Revision: 20210104
    • Publication Date:
      20221213
    • Accession Number:
      10.1210/clinem/dgz234
    • Accession Number:
      31778170