The beneficial effects of adding metformin to standard treatment in newly diagnosed metastatic prostate cancer

08 Jul 2025

Adding the drug metformin, a safe and widely-used medication for diabetes, to current treatments for newly diagnosed metastatic prostate cancer has been shown, for the first time, to be beneficial for patients. Results published in Lancet Oncology yesterday from the STAMPEDE trial, one of the world’s largest and most successful prostate cancer trials, show evidence of benefit in men with this condition.

Between 2016 and 2023, 1,874 men with metastatic prostate cancer joined the metformin part of the STAMPEDE trial. Only non-diabetic men could take part. Researchers randomly assigned the men to two groups: 938 received the current standard-of-care treatment only, while 936 received metformin as well as their standard-of-care treatment. The current standard-of-care for metastatic prostate cancer includes testosterone-lowering therapy called Androgen Deprivation Therapy (ADT). Most patients also received chemotherapy using the drug docetaxel as part of their standard treatment.

Adding metformin had a universally beneficial effect in reducing the common and often distressing side-effects of ADT, a treatment required for all men with this type of cancer. After two years of therapy, patients who received standard treatment plus metformin had gained less than half as much weight (2kg) as those assigned to standard treatment only (4.4kg). They also had lower levels of cholesterol and blood sugar. Furthermore, fewer patients in the metformin group reported signs of metabolic syndrome, a group of health problems which increase the risk of developing type 2 diabetes and heart disease. Such effects may improve patients’ future quality of life and reduce the known long-term health risks to overall health associated with ADT.

The trial was designed to see whether adding metformin to standard care slowed down the development of the cancer and improved survival. The results did not demonstrate a statistically significant benefit for all those who took metformin. However, there was evidence that a proportion of men with the highest risk prostate cancer did potentially benefit from taking metformin. This anti-cancer effect was seen in men with the highest burden of cancer, the most lethal form of the disease. Although this finding was not statistically powered for a definitive conclusion, it is important to note that all measures of anti-cancer activity in this high-risk group, including survival, were improved by the addition of metformin to ADT. Metformin was also well tolerated, with the main side-effect being diarrhoea in some men.

Prostate cancer is the second most common cancer in the UK and the most common cancer in men, with more than 50,000 cases diagnosed annually in England and Wales alone. Of these, 19% have metastatic disease (where the cancer has spread to other parts of the body) when it is first diagnosed. This type of prostate cancer is usually treated with long-term hormone therapy (ADT), which will slow the progression of the disease in most men, often for a number of years. However, the ADT affects the body’s metabolism, leading to side-effects including weight gain and other adverse metabolic conditions such as diabetes, insulin resistance, disturbance of healthy blood lipid profiles and future development of cardiovascular disease. These adverse effects are not easily reversible. Metformin modifies the way the body processes energy from sugars and fats and is also known to reduce energy use in cancer cells, which are known to have a high requirement for energy to enable them to keep growing and moving.

Since the metformin comparison began, new-generation hormone therapy drugs have become more widely used in standard care. While effective at extending survival, these newer drugs carry an increased risk of heart problems compared to the older ADT drugs that most patients in this study received. This means the benefits of metformin may be even more relevant now.

Doctors and patients can use these results to help decide whether metformin might be right for them. Metformin is an inexpensive and safe drug, but the current drug license does not cover prostate cancer. This means it may not be immediately available within the NHS for use in men with prostate cancer.

The STAMPEDE trial began in 2005, and the metformin comparison opened in 2016. STAMPEDE finished recruiting nearly 12,000 participants across all comparisons in 2023. It took place across more than 100 hospitals in the UK and Switzerland. The study was funded by Cancer Research UK and the Medical Research Council, with further support from Prostate Cancer UK and pharmaceutical industry collaborators including Janssen, Astellas, Clovis Oncology, Novartis, Pfizer, and Sanofi-Aventis.

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