Exploring the clinical connections between epilepsy and diabetes mellitus: Promising therapeutic strategies utilizing agmatine and metformin.

Purpose: Diabetes mellitus (DM) and epilepsy and the psychological and socio-economic implications that are associated with their treatments can be quite perplexing. Metformin is an antihyperglycemic medication that is used to treat type 2 DM. In addition, metformin elicits protective actions against multiple diseases, including neurodegeneration and epilepsy. Recent studies indicate that metformin alters the resident gut microbiota in favor of species producing agmatine, an arginine metabolite which, in addition to beneficially altering metabolic pathways, is a potent neuroprotectant and neuromodulant.

Methods: We first examine the literature for epidemiological and clinical evidences linking DM and epilepsy. Next, basing our analyses on published literature, we propose the possible complementarity of agmatine and metformin in the treatment of DM and epilepsy.

Results: Our analyses of the clinical data suggest a significant association between pathogeneses of epilepsy and DM. Further, both agmatine and metformin appear to be multimodal therapeutic agents and have robust antiepileptogenic and antidiabetic properties. Data from animal and clinical studies largely support the use of metformin/agmatine as a double-edged pharmacotherapeutic agent against DM and epilepsy, particularly in their concurrent pathological occurrences.

Conclusion: The present review explores the evidences and available data on possible uses of metformin/agmatine as pertinent antidiabetic and antiepileptic agents. Our hope is that this will stimulate further research on the therapeutic actions of these multimodal agents, particularly for subject-specific clinical outcomes.