Metformin Use May Reduce Dementia Risk in Patients With Type 2 Diabetes

Patients with type 2 diabetes treated with metformin, a glycemic-lowering agent, had a significantly reduced risk of developing long-term dementia, according to study findings published in Alzheimer’s & Dementia.

Type 2 diabetes and insulin resistance are known modifiable risk factors for dementia. Antidiabetic drugs, in addition to maintaining euglycemia, may therefore possibly attenuate the development of a major neurocognitive disorder. For the study, researchers aimed to assess the association between metformin and dementia risk and compare this with patients with type 2 diabetes who do not use antidiabetic drugs.

Using the UK Clinical Practice Research Datalink (CPRD) database, the researchers conducted a population-based cohort on patients with type 2 diabetes aged 50 and older who were treated with metformin between 2001 and 2018. The comparison group consisted of patients with type 2 diabetes aged 50 and older with no antidiabetic drug prescription records. Inclusion criteria consisted of first-time metformin monotherapy users, verified by registration in CPRD for 1-year prior to the first prescription of metformin. Patients with dementia patients who had diagnoses unrelated to aging, such as HIV, or alcohol and drug-induced dementia, were excluded.

Patients were considered to have dementia if they either had a diagnosis of dementia in CPRD, a dementia diagnosis based on international classification of diseases (ICD) codes, or had at least one dementia-specific drug prescription.

The study’s primary outcome was the date of first dementia diagnosis, or the first date of a dementia-specific drug prescription, whichever occurred first.

The total population cohort consisted of 114,628 metformin users compared to a group of 95,609 patients with type 2 diabetes who weren’t users. Compared with nonusers, metformin users were found to be slightly younger, have a higher body mass index (BMI), and more likely to have cardiovascular disease. Additionally, metformin users had significantly higher HbA1c levels at baseline (8.3% vs 6.5%, P <.05).

Over a median follow up of 5 years, compared with the nonuser group, the metformin group was found to have lower incident dementia cases (6.0% vs 8.5%). Additionally, cox regression analysis found metformin combination therapy during the initial 5 years of treatment was associated with a lower dementia risk, when compared with metformin monotherapy (HR, 0.75; 95% CI, 0.69-0.81 vs HR, 0.70; 95% CI, 0.63-0.78, respectively).

Of note, subgroup analysis by age found a stronger effect of metformin in reducing dementia risk in patients younger than age 70 when compared with those aged 70 and older (HR, 0.77; 95% CI, 0.69–0.85 vs HR, 0.91; 95% CI, 0.87–0.96).

Study limitations included the underreporting or undiagnosed patients with dementia within the cohort, which may have led to bias. Confounding bias cannot be ruled out, as data on educational attainment, or physical activity, is lacking.

The researchers wrote “[T]his population-based cohort study provides strong epidemiological evidence of a beneficial role of metformin on dementia risk in T2D [type 2 diabetes] patients, going beyond its glycemic effect.” “Our results add credence to the potential generalizability and repurposing of metformin for primary and secondary dementia prevention,” they concluded.