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October 31, 2017; 89 (18) Article

Metformin vs sulfonylurea use and risk of dementia in US veterans aged ≥65 years with diabetes

Ariela R. Orkaby, Kelly Cho, Jean Cormack, David R. Gagnon, Jane A. Driver
First published September 27, 2017, DOI: https://doi.org/10.1212/WNL.0000000000004586
Ariela R. Orkaby
From the VA Boston Geriatric Research, Education, and Clinical Center (GRECC) and Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC) (A.R.O., K.C., J.C., D.R.G., J.A.D.); Division of Aging (A.R.O., K.C., J.A.D.), Brigham & Women's Hospital, Harvard Medical School; and Boston University School of Public Health Department of Biostatistics (D.R.G.), MA.
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Kelly Cho
From the VA Boston Geriatric Research, Education, and Clinical Center (GRECC) and Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC) (A.R.O., K.C., J.C., D.R.G., J.A.D.); Division of Aging (A.R.O., K.C., J.A.D.), Brigham & Women's Hospital, Harvard Medical School; and Boston University School of Public Health Department of Biostatistics (D.R.G.), MA.
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Jean Cormack
From the VA Boston Geriatric Research, Education, and Clinical Center (GRECC) and Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC) (A.R.O., K.C., J.C., D.R.G., J.A.D.); Division of Aging (A.R.O., K.C., J.A.D.), Brigham & Women's Hospital, Harvard Medical School; and Boston University School of Public Health Department of Biostatistics (D.R.G.), MA.
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David R. Gagnon
From the VA Boston Geriatric Research, Education, and Clinical Center (GRECC) and Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC) (A.R.O., K.C., J.C., D.R.G., J.A.D.); Division of Aging (A.R.O., K.C., J.A.D.), Brigham & Women's Hospital, Harvard Medical School; and Boston University School of Public Health Department of Biostatistics (D.R.G.), MA.
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Jane A. Driver
From the VA Boston Geriatric Research, Education, and Clinical Center (GRECC) and Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC) (A.R.O., K.C., J.C., D.R.G., J.A.D.); Division of Aging (A.R.O., K.C., J.A.D.), Brigham & Women's Hospital, Harvard Medical School; and Boston University School of Public Health Department of Biostatistics (D.R.G.), MA.
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Citation
Metformin vs sulfonylurea use and risk of dementia in US veterans aged ≥65 years with diabetes
Ariela R. Orkaby, Kelly Cho, Jean Cormack, David R. Gagnon, Jane A. Driver
Neurology Oct 2017, 89 (18) 1877-1885; DOI: 10.1212/WNL.0000000000004586

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Abstract

Objective: To determine whether metformin is associated with a lower incidence of dementia than sulfonylureas.

Methods: This was a retrospective cohort study of US veterans ≥65 years of age with type 2 diabetes who were new users of metformin or a sulfonylurea and had no dementia. Follow-up began after 2 years of therapy. To account for confounding by indication, we developed a propensity score (PS) and used inverse probability of treatment weighting (IPTW) methods. Cox proportional hazards models estimated the hazard ratio (HR) of incident dementia.

Results: We identified 17,200 new users of metformin and 11,440 new users of sulfonylureas. Mean age was 73.5 years and mean HbA1c was 6.8%. Over an average follow-up of 5 years, 4,906 cases of dementia were diagnosed. Due to effect modification by age, all analyses were conducted using a piecewise model for age. Crude hazard ratio [HR] for any dementia in metformin vs sulfonylurea users was 0.67 (95% confidence interval [CI] 0.61–0.73) and 0.78 (95% CI 0.72–0.83) for those <75 years of age and ≥75 years of age, respectively. After PS IPTW adjustment, results remained significant in veterans <75 years of age (HR 0.89; 95% CI 0.79–0.99), but not for those ≥75 years of age (HR 0.96; 95% CI 0.87–1.05). A lower risk of dementia was also seen in the subset of younger veterans who had HbA1C values ≥7% (HR 0.76; 95% CI 0.63–0.91), had good renal function (HR 0.86; 95% CI 0.76–0.97), and were white (HR 0.87; 95% CI 0.77–0.99).

Conclusions: After accounting for confounding by indication, metformin was associated with a lower risk of subsequent dementia than sulfonylurea use in veterans <75 years of age. Further work is needed to identify which patients may benefit from metformin for the prevention of dementia.

GLOSSARY

ADA=
American Diabetes Association;
CI=
confidence interval;
eGFR=
estimating glomerular filtration rate;
HbA1c=
hemoglobin A1c;
HR=
hazard ratio;
ICD-9=
International Classification of Diseases–9;
IPTW=
inverse probability of treatment weighting;
MCI=
mild cognitive impairment;
PS=
propensity score;
VA=
Veterans Administration;
VaD=
vascular dementia

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at Neurology.org

  • Editorial, page 1848

  • Received December 20, 2016.
  • Accepted in final form August 1, 2017.
  • © 2017 American Academy of Neurology
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