Metformin Beyond Diabetes: Exploring Off-Label Applications across Medical Frontiers

Abstract

Metformin, widely used for T2D, is increasingly explored for off-label use in both endocrine and non-endocrine conditions, showing promise for improving patient outcomes. In polycystic ovary syndrome, metformin has demonstrated efficacy in lowering anti-Müllerian hormone levels and improving hormonal and metabolic parameters, though its role in managing hirsutism, especially in adolescents, remains uncertain. In gestational diabetes mellitus, metformin effectively reduces maternal weight gain, lowers the risk of preeclampsia, neonatal hypoglycemia, and macrosomia, and improves glycemic control without affecting fetal neurodevelopment. Beyond endocrine disorders, metformin's broader applications are under investigation. Although early observational studies suggested that metformin reduces cancer risk in diabetics, subsequent analyses revealed significant biases, and randomized clinical trials found no anticancer benefit. This highlights the need for caution when interpreting observational data and the importance of robust randomized trials to assess metformin's true impact on cancer outcomes. In cardiovascular diseases, metformin shows promise in reducing mortality and adverse cardiovascular events. Research also suggests metformin's potential to protect against diabetic kidney disease and neurodegenerative conditions such as Alzheimer's and Parkinson's diseases. However, additional studies are needed to better understand and enhance metformin's clinical effectiveness across various patient groups.