July 12, 2024
Stopping Metformin Early Increases Dementia Risk in Older Adults with Type 2 Diabetes

Stopping Metformin Early Increases Dementia Risk in Older Adults with Type 2 Diabetes

A recent study published in JAMA Network Open has found that stopping treatment with the diabetes drug metformin early is associated with a higher risk of developing dementia in older adults with type 2 diabetes (T2D).

Metformin is commonly used as the first-line treatment for T2D. Previous studies have suggested that starting metformin treatment may decrease the risk of developing dementia in individuals with type 2 diabetes.

However, due to side effects such as gastrointestinal issues and kidney problems, many patients discontinue their metformin treatment. In fact, one-fifth of early users choose to use alternative antidiabetic drugs instead of continuing with metformin.

According to current recommendations, the benefits and risks of metformin therapy should be carefully considered when a person’s estimated glomerular filtration rate (eGFR) falls below a certain threshold.

In the study, researchers analyzed electronic health records (EHRs) of a cohort of metformin users who were enrolled in the Kaiser Permanente Northern California (KPNC) healthcare system. The cohort consisted of older adults born before January 1, 1955, who had used metformin, did not have dementia, and had completed a health survey.

The follow-up for dementia incidence began in 1996 and continued until 2020. The researchers compared participants who discontinued metformin early for reasons unrelated to kidney dysfunction to those who continued with regular metformin use.

The study used an emulated trial design, which replicated critical features of a randomized controlled trial (RCT). Early terminators of metformin were matched with routine users in terms of age, gender, and duration of diabetes.

The results showed that early terminators of metformin were 1.21 times more likely to be diagnosed with dementia compared to the matched routine users.

Mediation analysis revealed that changes in hemoglobin A1c (HbA1c) levels and insulin use partially mediated the association between early metformin termination and dementia. However, the contribution of these factors was minimal.

The study’s large sample size and long follow-up period allowed for precise estimates of the association between early metformin termination and dementia risk. The design of the study also minimized potential confounding factors.

These findings have important implications for the clinical management of diabetes, particularly in older adults. Rather than discontinuing metformin, individuals with diabetes at a higher risk of dementia might benefit from managing the adverse effects or switching to other formulations of metformin.

Future studies could further investigate the association between metformin and dementia risk in different populations and evaluate the potential benefits in prediabetic individuals.


  1. Source: Coherent Market Insights, Public sources, Desk research
  2. We have leveraged AI tools to mine information and compile it