Association Between Metformin Initiation and Incident Dementia Among African American and White Veterans Health Administration Patients

Jeffrey F. Scherrer, PhD; John E. Morley, MBBCh; Joanne Salas, MPH; James S. Floyd, MD; Susan A. Farr, PhD; Sascha Dublin, MD


Ann Fam Med. 2019;17(4):352-362. 

In This Article

Abstract and Introduction


Purpose: African American patients are more likely to experience cognitive decline after type 2 diabetes mellitus onset than white patients. Metformin use has been associated with a lower risk of dementia compared with sulfonylureas. Evidence for whether this association differs by race is sparse.

Methods: Veterans Health Administration (VHA) medical record data were obtained for 73,761 African American and white patients aged ≥50 years who used the VHA from fiscal years 2000 to 2015. Patients were free of dementia and diabetes medications during fiscal years 2000 and 2001 and subsequently initiated metformin or sulfonylurea monotherapy. For race and age subgroups, Cox proportional hazards models using propensity scores and inverse probability of treatment weighting to control for confounding were computed to measure the association between metformin vs sulfonylurea initiation and incident dementia.

Results: After controlling for confounding, among patients aged ≥50 years, metformin vs sulfonylurea use was associated with a significantly lower risk of dementia in African American patients (hazard ratio [HR] = 0.73; 95% CI, 0.6–0.89) but not white patients (HR = 0.96; 95% CI, 0.9–1.03). The strongest magnitude of association between metformin and dementia was observed among African American patients aged 50 to 64 years (HR = 0.6; 95% CI, 0.45–0.81). Among those aged 65 to 74 years, metformin was significantly associated with lower risk of dementia in both races. Metformin was not associated with dementia in patients aged ≥75 years.

Conclusions: Metformin vs sulfonylurea initiation was associated with a substantially lower risk of dementia among younger African American patients. These results may point to a novel approach for reducing the risk of dementia in African Americans with type 2 diabetes mellitus.


Type 2 diabetes mellitus (T2DM) is almost twice as prevalent among African Americans as non-Hispanic whites. The age-adjusted prevalence of T2DM is 13.4% in African Americans and 7.3% in whites.[1] African American patients on average have worse glycemic control[2] and more diabetes-related complications than white patients.[3,4]

Diabetes is a risk factor for dementia,[5] and African Americans have nearly twice the incidence of dementia as whites.[6,7] This disparity is greater in patients aged 55 to 65 years compared with older patients.[8] The prevalence of dementia in patients with T2DM is 10% to 18% greater in African American patients compared with white patients.[9] Results from the Atherosclerosis Risk in Communities study indicate that African American participants with T2DM had a 41% decrease in cognitive test scores over a period of 14 years, whereas white participants experienced no decrease.[10]

Emerging evidence from observational studies with robust control for confounding suggests that a first-line diabetes medication, metformin, compared with sulfonylureas, is associated with an 8% to 10% decrease in dementia risk.[11,12] We are aware of 1 study that evaluated differences in the association between metformin and dementia between white and African American patients.[11] Among patients aged 65 to 74 years, metformin was significantly associated with lower dementia risk in white patients (hazard ratio [HR] = 0.87; 95% CI, 0.77–0.99) but not in African American patients (HR = 0.95; 95% CI, 0.66–1.38). That study did not include patients aged <65 years, and the findings might not apply to younger patients. The increased risk of cognitive decline in African Americans compared with whites is greatest in younger age groups (ie, a ged 55 to 64 years[8]), and African Americans are more likely than whites to experience diabetes onset before age 50.[13] Assuming metformin mitigates diabetes-related cognitive decline, the protective effects of metformin might be observed in younger patients not included in existing research.

The present study was designed to (1) determine if initiation of metformin, compared with sulfonylureas, is associated with a lower risk of dementia among white and African American patients aged ≥50 years, (2) determine if results change after controlling for glycemic burden or hypoglycemic events, and (3) evaluate drug associations with incident dementia in race and age subgroups.