Early Metformin Initiation Does Not Appear to Cut Dementia Risk

Initiating metformin earlier in patients with type 2 diabetes (T2D) does not appear to prevent cognitive decline, according to the findings of a recently published retrospective cohort study. 

Previous research has suggested that treatment with metformin may potentially lower the risk of dementia, however whether the timing of treatment impacts this result remains unclear. To examine the association between metformin initiation and dementia risk, study authors utilized electronic health records obtained from 2 large healthcare systems: the Veteran Health Affairs (VHA; N=112,845) and Kaiser Permanente Washington (KPW; N=14,333). 

Patients included in the analysis were required to be ≥50 years old, have a hemoglobin A1c (HbA1c) between 6.5 and <9.5mg/dL, and have no history of either dementia or fills for antidiabetic medications prior to the cohort entry.

“Initiators started metformin monotherapy and noninitiators used no antidiabetic medications in the 6 months after the first qualifying HbA1c,” the study authors explained. Incident dementia was the primary outcome of the study. Confounding was controlled using propensity scores as well as inverse probability of treatment weighting (IPTW) in Cox proportional hazards models.

The study authors reported that there were 7547 new dementia cases in VHA during a median follow-up of 6.2 years and 1090 new cases in KPW during a median follow-up of 6.8 years. “After IPTW, there was no association between initiation of metformin (vs no initial treatment) and incident dementia in VHA (HR 1.04; 95% confidence interval [CI], 0.95-1.13) or KPW (HR 0.81; 95% CI, 0.51-1.28),” the authors stated. 

Additionally, it was found that these results did not differ based on a patient’s age, baseline HbA1c, or race. 

“Results do not support initiating metformin earlier to prevent cognitive decline and, thus, may dampen enthusiasm for metformin as a potential antidementia drug,” the authors concluded. They did suggest, however, that conducting  randomized clinical trials may help “clarify” the effect metformin has on cognitive decline in T2D patients. 

Reference

Salas J, Morley JE, Scherrer JF, et al. Risk of incident dementia following metformin initiation compared with noninitiation or delay of antidiabetic medication therapy [published online May 3, 2020]. Pharmacoepidemiology & Drug Safety. DOI 10.1002/pds.5014.