New research has uncovered an intriguing association between the cessation of metformin treatment for reasons unrelated to kidney dysfunction and the incidence of dementia among individuals with diabetes. While prior studies hinted at metformin's potential to reduce dementia risk, this study delves into the effects of discontinuing metformin therapy. This study was published in JAMA Network Open by Scott C. Zimmerman and colleagues.


The study, conducted at Kaiser Permanente Northern California, involved a cohort of individuals born before 1955 who were metformin users without a history of kidney disease when they initiated the treatment. Dementia follow-up commenced with the implementation of electronic health records in 1996 and extended through 2020.
Researchers focused on a group of early terminators, comprising 12,220 individuals who discontinued metformin despite maintaining a normal estimated glomerular filtration rate (eGFR). These early terminators were compared with routine metformin users, who either continued metformin treatment or had terminated it (with or without restarting) after an abnormal eGFR measurement. Early terminators were matched with routine users of the same age and gender who had diabetes for the same duration.
The final analytic sample included 12,220 early terminators, of which 5,640 were women (46.2% of the group). The mean (SD) age at the start of the first metformin prescription for early terminators was 59.4 (9.0) years.
The routine user group comprised 29,126 individuals, with 13,582 women (46.6% of the group). The mean (SD) age at the start of the first metformin prescription for routine users was 61.1 (8.9) years.
Early terminators had a 21% higher hazard of dementia diagnosis compared to routine users (hazard ratio: 1.21; 95% CI: 1.12 to 1.30).
Mediation analysis examined whether changes in HbA1c level or insulin use explained the association between early metformin termination and dementia incidence.
The contribution of these factors to the association was minimal and ranged from no contribution for insulin use at 5 years after termination to 0.07 years for HbA1c level at 1 year after termination.
This suggests that the association between early termination of metformin and dementia incidence was largely independent of changes in HbA1c level and insulin usage.
In conclusion, this research highlights an intriguing relationship between metformin treatment and dementia risk among diabetes patients. It suggests that the termination of metformin therapy for reasons unrelated to kidney dysfunction may increase the risk of developing dementia. These findings could hold significant implications for the clinical management of adults with diabetes, offering additional evidence of metformin's potential in reducing dementia risk.
This study underscores the importance of further exploration of the complex relationship between metformin and dementia risk. It opens doors to future investigations that could elucidate the underlying mechanisms and potentially lead to improved clinical treatments for diabetes patients.
Reference:
Zimmerman, S. C., Ferguson, E. L., Choudhary, V., Ranatunga, D. K., Oni-Orisan, A., Hayes-Larson, E., Duarte Folle, A., Mayeda, E. R., Whitmer, R. A., Gilsanz, P., Power, M. C., Schaefer, C., Glymour, M. M., & Ackley, S. F. Metformin cessation and dementia incidence. JAMA Network Open,2023;6(10):e2339723. https://doi.org/10.1001/jamanetworkopen.2023.39723