Some Metformin-Based Therapies May Lower Dementia Risk in Type 2 Diabetes

Although risk for dementia among patients with type 2 diabetes varies with oral antihyperglycemic regimens, certain metformin (MET)-based combinations appear to provide greater protection, according to study results published in Alzheimer’s & Dementia.

Researchers explored whether various MET-based oral combination therapies influence the risk for dementia in patients newly diagnosed with type 2 diabetes mellitus (T2DM). They conducted a retrospective, population-based cohort study using data from Taiwan’s National Health Insurance Research Database, spanning the years 2000 to 2018.

A total of 44,073 adults with newly diagnosed T2DM were identified and categorized into 4 groups based on their initial combination therapy:

• MET-sulfonylureas (SU; n=35,443)
• MET-thiazolidinediones (TZD; n=2046)
• MET-dipeptidyl peptidase-4 inhibitors (DPP4i; n=4519)
• MET-glinides (n=2065)

Baseline characteristics were generally balanced across groups. The average age was approximately 60 years, and about half of participants were men. More than one-third of patients in each cohort were aged at least 65 years, and the mean Charlson Comorbidity Index score ranged between 2 and 3. Common comorbidities included hypertension and hyperlipidemia.

In adjusted analyses, compared with the MET-SU reference group, patients treated with MET-TZD (hazard ratio [HR], 0.73; 95% CI, 0.57-0.94) and MET-DPP4i (HR, 0.64; 95% CI, 0.52-0.79) had a significantly reduced risk of developing dementia. In contrast, the MET-glinides group demonstrated a nonsignificant increased risk (HR, 1.14; 95% CI, 0.94-1.39). Relative risk calculations similarly showed the lowest dementia incidence with MET-DPP4i, followed by MET-TZD, whereas MET-glinides carried the highest risk.

Long-term follow-up using Kaplan-Meier analysis demonstrated clear separation between the groups. At 15 years, the MET-DPP4i group had the lowest cumulative dementia risk, followed by MET-TZD, while MET-glinides showed the greatest risk. Subgroup analyses further indicated that age greater than 65 years, a higher comorbidity burden, and vascular risk factors such as heart failure, arrhythmia, and cerebrovascular disease increased risk for dementia.

This study was limited by its retrospective design, use of diagnostic codes, and reliance on administrative claims data, which restricted assessment of HbA_1c levels, medication adherence, lifestyle factors, and dementia subtypes.

“These findings may inform treatment decisions when considering long-term cognitive outcomes in patients with T2DM,” the study authors concluded.