Metformin Found to Reduce Risk of Dementia in T2DM 

Metformin found to reduce dementia risk in type 2 diabetes: could it potentially be the first medication approved to PREVENT dementia?

Recent observational studies have shown decreased rates of dementia among African American patients with diabetes taking metformin.

The prevalence of type 2 diabetes in African American people is nearly twice that of non-Hispanic whites. In addition, African Americans are often burdened with poorer glycemic control and more complications related to diabetes. Diabetes is a risk factor for dementia and it has been found that African Americans have twice the rate of dementia compared to whites. In the Atherosclerosis Risk in Communities study, white participants with T2DM were not found to experience any cognitive decline while African American participants with T2DM experienced an average of 41% decline in cognitive testing over 14 years. This matter is of particular interest following the release of study data indicating that metformin, the most commonly prescribed and readily available diabetes medication, is linked to improvements in risk for dementia among African American patients with T2DM. If this information were to lead to an additional indication for metformin to reduce risk of dementia in African American patients, or any patients with T2DM, it would be the first medication approved to prevent dementia.

Previous observational studies have shown that metformin decreases risk for dementia by 8%-10% when compared to sulfonylureas. One study sought to differentiate the benefit seen from metformin in African American versus white participants. Results displayed a significant decrease in risk for dementia in white patients aged 65-75 years (HR: 0.87, CI 0.77-0.99). No significant results applied to African American patients and the study did not include patients less than 65 years of age. These findings cannot be applied to younger patients, and as the greatest risk for cognitive decline in African American patients is during ages 55-64 years, there is a need for further studies to understand whether metformin has a role in preventing dementia for African American patients with T2DM during the most critical years.

A recent study was published with intent to determine if initiation of metformin compared with sulfonylureas is associated with lower risk for dementia among African American and white patients aged 50 years. This retrospective cohort study obtained patient medical records from the Veterans Health Administration for a total of 15 years. At baseline, the 73,761 white (85.7%) or African American (14.3%) patients had no documented evidence of dementia and had just initiated their first antidiabetic medication: metformin or a sulfonylurea.

For patients under the age of 75, the rate of dementia was lower among metformin users compared to sulfonylurea users. After initiating metformin in those older than 50 years old, the unadjusted incidence rate among white participants was 10.1/1,000 patient years; 7.3/1,000 patient years among African American patients. Among sulfonylurea users older than 50 years, the unadjusted incidence rate among white participants was 15.4/1,000 patient years; 12.6/1,000 patient years among African American patients. What the results translate to is: among African American patients aged 50-64 years old, metformin use was associated with a 40% lower risk of dementia; and with a 29% lower risk among African American patients aged 65-74 years old. Among the white population, those aged 65-74 had a significantly lower risk of dementia using metformin.

Within the African American population, metformin may deter development of dementia when used as early as possible. As first line anti-diabetic therapy, metformin is normally prescribed early on in diabetes management, and should be considered as early as possible when prediabetes or new onset diabetes arises in African American patients. Further clinical trials would be helpful to determine whether metformin could have a potential role for prevention of dementia in high risk patients within other populations, outside of African Americans and type 2 diabetes patients.

Practice Pearls:

• African American patients develop type 2 diabetes at a rate twice that of white patients; their risk for developing type 2 diabetes and dementia is 10%-18% greater than white patients.
• Recent studies have displayed significant reduction of risk for developing dementia in African American patients with type 2 diabetes, aged 50-74 years old, from taking metformin.
• Based on these studies, metformin may offer great reduction in risk for developing dementia when initiated early on, such as during prediabetes in younger African American patients.

Scherrer, Jeffrey F., et al., “Association Between Metformin Initiation and Incident Dementia Among African American and White Veterans Health Administration Patients.” The Annals of Family Medicine, vol. 17, no. 4, 2019, pp. 352–362., doi:10.1370/afm.2415.

Orkaby AR, Cho K, Cormack J, Gagnon DR, Driver JA. Metformin vs sulfonylurea use and risk of dementia in US veterans aged ≥65 years with diabetes. Neurology. 2017;89(18):1877-1885. 


Scherrer JF, Salas J, Floyd JS, Farr SA, Morley JE, Dublin S. Metfor- min and sulfonylurea use and risk of incident dementia. Mayo Clin Proc. In press; 2019. 


Amber Satz, PharmD Candidate, LECOM School of Pharmacy