• Ariela R Orkaby, Kelly Cho, Jean Cormack, David R Gagnon, and 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. aorkaby@partners.org.
• Neurology. 2017 Oct 31; 89 (18): 1877-1885.

ObjectiveTo determine whether metformin is associated with a lower incidence of dementia than sulfonylureas.MethodsThis 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.ResultsWe 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).ConclusionsAfter 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.© 2017 American Academy of Neurology.

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