The Role of Metformin in Skeletal Muscle Healing: A Comprehensive Review

Background: Skeletal muscle disorders, which comprise numerous rare diseases, are primarily genetic. To improve patients’ quality of life, novel treatment discovery for neuromuscular illness is needed, given the psychological and financial strain caused by the disease’s progression and limited therapeutic options. Metformin has garnered attention beyond its glucose lowering effects for its ability to improve skeletal muscle repair. Therefore, this review aims to gather and evaluate recent studies on the impact of metformin on the regeneration of skeletal muscle. Methods: A systematic search was conducted in January 2025 using multiple databases (i.e., ScienceDirect, Scopus, Web of Science, IEEE, and others) to identify primary research that focused on the effects of metformin on skeletal muscle or mechanism related to skeletal muscle healing. After applying exclusion criteria, the abstracts were screened to assess their eligibility for the review, followed by full-text screening. Results: A total of 115 studies were identified, and 40 studies were included in the final data synthesis. Metformin’s ability on muscle healing involved satellite cell activation, inflammatory modulation, and mitochondrial regulation. Research results are still inconsistent; some studies show that it positively impacts regeneration, while others show delayed healing or compromised function. Metformin has various effects on the repair of skeletal muscle; most of which are mediated by AMPK activation, decreased inflammation, and oxidative stress regulation. Conclusion: This review highlights the potential of metformin in skeletal muscle healing. Nevertheless, the type of injury, dosage, and timing of administration are critical factors influencing outcomes.