# Repurposing metformin for cardioprotection: mechanisms and therapeutic potential across cardiovascular pathologies

## TL;DR

This paper reviews how metformin, a diabetes drug, protects the heart through multiple biological pathways and could be repurposed for various heart conditions.

## Contribution

The paper provides a comprehensive review of metformin's cardioprotective mechanisms and translational potential across diverse cardiovascular diseases.

## Key findings

- Metformin exerts cardioprotective effects via both AMPK-dependent and AMPK-independent pathways.
- It modulates mitochondrial function, oxidative stress, and inflammation in cardiac conditions like heart failure and ischemia.
- Evidence from preclinical and clinical studies supports metformin's potential for treating diabetic cardiomyopathy and anthracycline-induced cardiotoxicity.

## Abstract

Metformin, a cornerstone therapy for type 2 diabetes mellitus, has emerged as a promising cardioprotective agent with effects that extend well beyond glycemic control. This review synthesizes current evidence on the molecular and cellular mechanisms underlying metformin’s glycemic control and cardiovascular benefits, highlighting both AMPK-dependent and AMPK-independent pathways. We examine its modulation of mitochondrial function, oxidative stress, inflammation, autophagy, and apoptosis across major cardiac conditions, including ischemia/reperfusion injury, heart failure, diabetic cardiomyopathy, and anthracycline-induced cardiotoxicity. By integrating evidence from both preclinical and clinical studies, we evaluate the translational potential of metformin’s pleiotropic actions across specific cardiac pathologies and outline key directions for future research and therapeutic innovation. Together, these insights highlight metformin’s promise in reshaping cardiovascular care beyond its traditional role in diabetes management.