Metformin Use Lowers Dementia Risk in Patients With Type 2 Diabetes

Metformin use decreases dementia risk among patients with type 2 diabetes; however, additional factors such as the use of antidepressants, nonsteroidal anti-inflammatory drugs (NSAIDs), and the presence or absence of neuropsychiatric disorders can influence the treatment effects of metformin on dementia risk. These are the findings of a study published in Alzheimer’s & Dementia.

Researchers at the University of Florida in Gainesville, University of Pittsburgh, and Rice University conducted a retrospective, longitudinal, observational, cohort study, collecting information from 1393 participants (38.8% men) aged 50 and older (mean age, 71.8) with type 2 diabetes from the National Alzheimer’s Coordinating Center (NACC) database between September 2005 and June 2021. They analyzed how treatment with metformin affected dementia risk in this patient population.

At baseline, all eligible participants exhibited normal cognitive functioning. During the study period, 754 (54.1%) participants took metformin — 396 on metformin monotherapy and 358 on metformin combination therapy. The remaining 639 (45.9%) did not take metformin for their type 2 diabetes.

Over a median follow-up of 4 years, 104 (7.5%) of the 1393 participants with type 2 diabetes developed dementia. Individuals treated with metformin demonstrated a significantly lower risk for dementia than nonusers (risk difference [RD], -3.2%; 95% CI, -6.2% to -0.2%).

The researchers identified 4 subgroups of participants with varying degrees of metformin treatment effects. Metformin use significantly decreased dementia risk in the subgroup of individuals without neuropsychiatric disorders who did not take NSAIDs (RD, -8.7%; 95% CI, -13.4% to -4.1%). In contrast, metformin use significantly increased dementia risk in the subgroup of individuals with neuropsychiatric disorders who did not take antidepressants (RD, 8.6%; 95% CI, 1.8% to 15.5%).

Individuals without neuropsychiatric disorders who took NSAIDs and metformin did not demonstrate a significant decrease in dementia risk (RD, -2.0%; 95% CI, -7.0% to 3.0%). Similar nonsignificant results were seen in participants with neuropsychiatric disorders who took antidepressants and metformin (RD, -4.6%; 95% CI, -12.3% to 3.1%).

“This study supports a significant association between metformin use and a reduced risk of dementia in individuals with T2D [type 2 diabetes],” the researchers concluded. “Our findings suggest that important factors, such as neuropsychiatric disorders, antidepressant use, and NSAIDs can assist in making personalized decisions regarding the use of metformin in people with T2D, particularly for those at high risk of dementia.”

Study limitations included potential selection and immortal time biases, a cohort consisting only 3.4% of the full NACC sample. This led to poor internal validity, limited generalizability to the patients with diabetes within the community, reliance on self-reported medical history including metformin use, and glycated hemoglobin as a confounding factor that influenced the strength of the diabetes to dementia association.

Disclosures: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see original source for full list of disclosures.