Farmacja Polska · Oct 29, 2026
Emerging molecular targets of metformine – current knowledge and therapeutic prospects
By Nagrodzki W, Niźinska K, Kapral M et al.
SUBJECT OF THE RESEARCH: This study concerns metformin—one of the key first-line drugs for treating type 2 diabetes. This compound is characterized by multidirectional activity that extends beyond its hypoglycemic action. Metformin is currently being intensively studied for its potential use in treating other conditions. OBJECTIVE: The main objective of this work is to present the current therapeutic use of metformin and assess the possibilities for its repurposing. This work also aims to identify research challenges and prospects for the further development of therapies using metformin. MATERIALS AND METHODS: The methodological basis of the research presented was the systematic selection and analysis of the latest literature on the subject. The following databases were used to identify the most important articles (in Polish and English): PubMed, Google Scholar, ResearchGate, and Scopus. The work included original publications, reports of clinical studies, review articles, and meta-analyses presenting the characteristics of metformin, its mechanisms of action (with particular emphasis on activation of the AMPK kinase pathway), its broad spectrum of clinical applications, and its repurposing potential. The search process used keywords such as: “metformin”; “repurposing”; “cancer”; “migraine”; “neurodegenerative disease”; “microbiota”. RESULTS: For many years, the effects of metformin on cells were thought to be limited exclusively to activation of AMPK kinase and inhibition of gluconeogenesis. It is now known that this drug affects various processes involved in cellular bioenergetics, proliferation, and differentiation, and also influences epigenetic changes and inflammatory pathways. The latest reports indicate the possibility of its repurposing in new therapeutic areas, including the treatment of cancers, neurodegenerative disorders, mental illnesses, and migraine. Current knowledge regarding the effects of metformin on gastrointestinal function and the gut microbiota was also discussed. CONCLUSIONS: The biological activity of metformin includes the regulation of many intracellular pathways. Owing to these properties, as well as its favorable safety profile and low treatment costs, this drug is a promising candidate for repurposing to treat other diseases. Nevertheless, introducing metformin for new indications faces significant challenges. For example, in the oncological context, a key problem is the discrepancy between the high concentrations used in in vitro studies and the concentrations achievable in clinical settings. A full assessment of the efficacy of metformin in the potential applications discussed in the article requires rigorous randomized clinical trials.