Metformin, Other Antidiabetic Drugs, and Risk of Alzheimer's Disease: A Population-Based Case–Control Study

Authors

  • Patrick Imfeld MSc,

    1. Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland
    2. Hospital Pharmacy, University Hospital Basel, Basel, Switzerland
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  • Michael Bodmer MD,

    1. Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland
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  • Susan S. Jick DSc,

    1. Boston Collaborative Drug Surveillance Program, School of Medicine, Boston University, Lexington, Massachusetts
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  • Christoph R. Meier PhD

    Corresponding author
    1. Hospital Pharmacy, University Hospital Basel, Basel, Switzerland
    2. Boston Collaborative Drug Surveillance Program, School of Medicine, Boston University, Lexington, Massachusetts
    • Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland
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Address Correspondence to Prof. Dr. Christoph R. Meier, Basel Pharmacoepidemiology Unit, Hospital Pharmacy, University Hospital Basel, Spitalstrasse 26, CH-4031 Basel, Switzerland. E-mail: meierch@uhbs.ch

Abstract

Objectives

To explore the risk of developing Alzheimer's disease (AD) in individuals with diabetes mellitus treated with metformin or other antidiabetic drugs.

Design

Case–control study.

Setting

The United Kingdom–based General Practice Research Database (GPRD), a well-established primary care database.

Participants

Seven thousand eighty-six individuals aged 65 and older with an incident diagnosis of AD identified between 1998 and 2008 and the same number of matched controls without dementia. Matching criteria were age, sex, general practice, calendar time, and years of history in the database.

Measurements

Comparison of previous use of metformin or other antidiabetic drugs between cases and controls and calculation of corresponding odds ratios (ORs) with 95% confidence intervals (CIs), using conditional logistic regression. Risk estimates were stratified according to duration of use and adjusted for potential confounders.

Results

As compared with nonusers, long-term users of 60 or more metformin prescriptions were at greater risk of developing AD (adjusted OR (AOR) = 1.71, 95% CI = 1.12–2.60), but there was no consistent trend with increasing number of prescriptions. Long-term use of other antidiabetic drugs such as sulfonylureas (AOR = 1.01, 95% CI = 0.72–1.42), thiazolidinediones (AOR = 0.87, 95% CI = 0.31–2.40), or insulin (AOR = 1.01, 95% CI = 0.58–1.73) was not related to an altered risk of developing AD.

Conclusion

Long-term use of sulfonylureas, thiazolidinediones, or insulin was not associated with an altered risk of developing AD. There was a suggestion of a slightly higher risk of AD in long-term users of metformin.

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