Metformin's Potential Beyond Diabetes: Exploring Diverse Health Benefits

Metformin, a frontline treatment for type 2 diabetes, has long been a pharmaceutical mainstay, with over 91 million prescriptions in 2021 alone. However, recent evidence suggests that metformin's efficacy extends beyond diabetes management, encompassing various conditions such as cancer, obesity, liver disease, cardiovascular issues, neurodegenerative disorders, and renal diseases. As research expands, numerous trials are underway to validate and explore new applications for the drug.

Metformin's history dates back to its recognition in 1918 for lowering blood glucose, followed by a period of neglect in the 1930s due to toxicity concerns. Rediscovered and synthesized in the 1940s, it was first used for diabetes in 1957 and gained U.S. approval in 1994. Since 2011, it has held its place as the preferred first-line treatment for type 2 diabetes.

While metformin's insulin-sensitizing effects have been a focal point, recent interest has surged due to its potential impacts on multiple receptors. The drug's efficacy in reducing coronary artery disease and protecting against cancer has garnered significant attention.

One groundbreaking study is the VA-IMPACT trial, led by Dr. Gregory G. Schwartz, testing metformin's effect on death and cardiovascular events in patients with prediabetes and established cardiovascular disease. This placebo-controlled trial, launched in 2023, aims to demonstrate metformin's potential to reduce cardiovascular morbidity and mortality.

Another promising avenue is metformin's role in cancer prevention. Dr. Sai Yendamuri is leading a phase 2 trial exploring metformin's ability to prevent lung cancer in individuals with overweight or obesity. The study also investigates whether metformin can reprogram the immune system to reduce regulatory T cells linked to tumor development.

Cognitive function preservation is another area of interest, with a phase 2/3 trial led by Dr. José A. Luchsinger assessing metformin's potential in preventing Alzheimer's disease. Preliminary results are expected in late 2026.

While metformin is currently FDA-approved for type 2 diabetes, off-label uses are under investigation, including obesity, gestational diabetes, weight gain from antipsychotics, and polycystic ovary syndrome.

Despite metformin's generally favorable safety profile, concerns about adverse effects, such as gastrointestinal issues, potential vitamin B12 deficiency, and rare risks like lactic acidosis, underscore the need for caution. Additionally, recent reports of certain long-acting metformin formulations containing carcinogenic substances emphasize the importance of refining formulations before considering metformin for widespread use beyond diabetes.