Neurodegenerative diseases is an umbrella term, encompassing many central nervous system degenerative disorders, including dementia, mild cognitive impairment, Alzheimer’s disease, and Parkinson disease.¹ A glance through the epidemiological data revealed high risk of these diseases like Alzheimers in people with diabetes.² These disorders occur due to progressive degeneration or/and death of neurons, and currently do not have a disease-specific cure.However, research in this domain has shown that some hypoglycemic drugs like metformin may act on the pathogenesis of neurodegenerative diseases and prove to be beneficial.¹

Metformin is a widely used agent for the treatment of diabetes. Apart from its hypoglycemic activity, it exhibits anti-oxidant and anti-inflammatory actions, helps in improving serum lipid profiles, and positively influences the process of hemostasis. Although the precise mechanisms underlying the benefits of metformin in neurodegenerative diseases such as Alzheimer’s remain unclear, investigators have demonstrated that activation of 5-adenosine monophosphate-activated protein kinase-dependent pathways in neural stem cells is likely to be responsible for its neuroprotective properties. In addition, it has been reported that it significantly reduces Beta-secretase 1 (BACE1) protein expression and activity in cell culture models and in vivo, thereby decreasing BACE1 cleavage products and production of beta-amyloid. Besides, some studies have shown that it decreases the activity of acetylcholinesterase, which is responsible for degrading acetylcholine, a neurotransmitter implicated in the process of learning and memory.²

Accruing clinical data suggests that long term use of metformin in diabetic individuals contributes to better cognitive function, contrary to those taking other anti-diabetic drugs.² A retrospective longitudinal study assessed the link between metformin therapy and risk of neurodegenerative diseases among elderly individuals with type 2 diabetes mellitus. The results showed that the incidence rate of neurodegenerative diseases was 11.48 per 1000 person-years among patients who were administered metformin, in comparison to 25. 45 per 1000 person-years in those who were not given metformin. It is noteworthy that 2–4 years and more than 4 years of metformin therapy were remarkably linked with lower risk of neurodegenerative diseases. The researchers of this study stated that long-term metformin therapy (>2 years) is associated with lower incidence of neurodegenerative diseases among elderly with type 2 diabetes.³ Given the beneficial actions of metformin, it stands out as a potential therapy for neurodegenerative diseases.

References

1. Ping F, Jiang N, Li Y. Association between metformin and neurodegenerative diseases of observational studies: systematic review and meta-analysis. BMJ Open Diabetes Res Care. 2020;8(1):e001370.
2. Markowicz-Piasecka M, Sikora J, Szydłowska A et al. Metformin - a Future Therapy for Neurodegenerative Diseases: Theme: Drug Discovery, Development and Delivery in Alzheimers Disease Guest Editor: DavideBrambilla. Pharm Res. 2017;34(12):2614-2627.
3. Shi Q, Liu S, Fonseca VA, et al. Effect of metformin on neurodegenerative disease among elderly adult US veterans with type 2 diabetes mellitus. BMJ Open. 2019;9(7):e024954.