Metformin adherence lowers dementia risk in patients with type 2 diabetes

Metformin has remained among the most popular oral hypoglycemic drugs for the past 60 years. It is still the first-line medication for the initial therapy for most patients with type 2 diabetes mellitus (T2DM). In recent years, the approval of a large number of new hypoglycemic drugs has brought more options for the therapy of T2DM patients, including DPP-4i (dipeptidyl peptidase-4 inhibitors), GLP-1RA (glucagon-like peptide 1 receptor agonists), and SGLT-2i (sodium-glucose cotransporter 2 inhibitors).

Metformin is a commonly used first-line drug for patients with type 2 diabetes and has several benefits other than lowering blood sugar levels. However, since the launch of powerful glucose-lowering anti-glycemic agents, the metformin-retained regimen has been challenged. Therefore, Po-Chih Chen from Taipei Medical University, Taipei, Taiwan, and colleagues investigated the association between metformin adherence and the risk of Parkinson's disease (PD) and dementia in a population-based cohort study.

For this purpose, the researchers identified diabetic patients with metformin-included combination anti-glycemic therapy from the National Health Insurance Research Database. The patients were then categorized into metformin-adherent and -nonadherent groups based on the medical record of the prescription's first year. Patients with severe diabetic complications, those contraindicated with metformin and having poor drug compliance were excluded. The study outcome was a diagnosis of Parkinson's disease or dementia.

The study led to the following findings:

• A total of 31,384 matched pairs were included after using propensity score matching, and both groups were followed up for an average of 5 years.
• Metformin adherence was linked with a remarkably lower dementia risk (adjusted hazard risk ratio (aHR)=0.72) but not PD (aHR=0.97).
• Subgroup analysis showed that the dementia risk was significantly reduced in metformin-adherent both male and female patients aged >65 or ≤ 65 years, and with or without concurrent insulin treatment.
• This effect was not impacted by concurrent insulin treatment, which may eliminate the bias due to the severity of diabetes mellitus.

"Despite the launch of several new oral anti-glycemic agents, metformin may provide further benefit in lowering dementia risk beyond conventional glycemic control as per the real-world evidence," the researchers concluded.

Reference:

Chen, P., Hong, C., Chen, W., Chan, L., & Chien, L. (2023). Metformin adherence reduces the risk of dementia in patients with diabetes: A population-based cohort study. Endocrine Practice. https://doi.org/10.1016/j.eprac.2023.01.007