Exploiting the cardioprotective potential of metformin against cardiotoxic agents.

Cardiotoxicity refers to impaired heart function, which can occur either directly or indirectly. The severity of cardiotoxicity depends on age, exposure duration, and the toxic agent involved. Metformin, primarily used in type 2 diabetic patients, exerts its antihyperglycemic effects by improving insulin sensitivity, suppressing hepatic glucose production, and reducing intestinal glucose absorption. Its cardioprotective properties have been demonstrated in several studies. Here, we reviewed the scientific literatures regarding the effect of metformin in preventing heart injury induced by cardiotoxic insults. A comprehensive search of scientific databases, including Web of Science, PubMed, Scopus, and Google Scholar, used relevant keywords to identify studies published up to April 2025. Metformin mitigated cardiotoxicity through various mechanisms, including reducing oxidative stress, increasing AMPK phosphorylation, inhibiting the NF-kB pathway, reducing inflammation, and regulating the autophagy and apoptosis pathways. This study highlights the potential cardioprotective efficacy of metformin against heart injury induced by various cardiotoxic agents.