A major international study has found that metformin, a common diabetes drug, does not improve survival in nondiabetic men with metastatic hormone-sensitive prostate cancer (mHSPC). The findings come from a phase 3 trial under the STAMPEDE platform, involving nearly 2,000 patients.
Although the drug helped reduce side effects linked to hormone therapy, it failed to meet the main goal of extending patients’ lives.
Metformin Doesn’t Improve Overall Survival
The trial tested whether adding metformin to standard treatment would help men live longer. Patients were randomly assigned to receive either the standard of care or standard care plus metformin (850 mg twice daily). The standard treatment included hormone therapy and often chemotherapy or drugs that block androgen receptors.
After five years of follow-up, researchers found no meaningful difference in survival. Men in the standard group lived a median of 61.8 months. Those who took metformin lived a median of 67.4 months. However, this difference was not statistically significant.
Out of 1,874 participants, 473 deaths occurred in the standard group and 453 in the metformin group. The hazard ratio was 0.91, with a P value of 0.15—showing no clear survival advantage for metformin.
There was also no improvement in prostate cancer–specific survival, progression-free survival, or failure-free survival in the overall group.
Possible Benefit in Patients with More Severe Disease
While the drug did not help the entire group live longer, researchers noticed a trend in patients with high-volume disease—those with more extensive cancer spread.
In this subgroup, men taking metformin had a hazard ratio of 0.79, with a P value of 0.0072. This suggests a possible benefit. However, it is not yet strong enough to change treatment guidelines. In men with low-volume disease, no benefit was seen.
Experts believe this signal deserves more study. It may lead to future research on whether certain groups of men with aggressive cancer might benefit from metformin.
Metformin Reduces Weight Gain and Improves Metabolic Health
One clear benefit from metformin was its effect on metabolism. Men taking metformin gained less weight while undergoing hormone therapy.
After two years, men on standard treatment gained an average of 4.4 kg. Those on metformin gained only 2.0 kg—a difference of 2.48 kg, which was statistically significant (P < .0001).
Metformin also improved blood sugar levels and cholesterol. It lowered fasting glucose, total cholesterol, LDL cholesterol, and HbA1c at 24, 48, and 104 weeks.
Side Effects and Safety
Metformin was generally safe, but more men experienced gastrointestinal issues like diarrhea and nausea.
- Diarrhea: 65% in the metformin group vs. 37% in the standard group
- Grade 3 diarrhea: 5% (metformin) vs. 3% (standard)
- Nausea: More common with metformin
Serious side effects (grade 3 or higher) occurred in 57% of the metformin group and 52% of the standard group. There was one drug-related death in the metformin group and six in the standard group.
Implications for Future Treatment
The results suggest that metformin should not be added to standard prostate cancer treatment just to improve survival. But the drug may still play a role in supporting men’s health during treatment.
Androgen-deprivation therapy (ADT), a key part of prostate cancer care, often causes weight gain, high cholesterol, and increased risk of diabetes or heart disease. Metformin may help ease these issues.
Researchers say the metabolic benefits of metformin are valuable and may improve quality of life. However, these benefits must be weighed against the risk of side effects, especially gastrointestinal discomfort.
What’s Next?
More research is needed to understand if metformin helps men with high-volume or aggressive disease. Studies may also explore if certain biomarkers can predict who benefits most.
A deeper look into how metformin affects cancer biology is underway through a metabolic substudy from the STAMPEDE platform.
Related topics:
Nubeqa (Darolutamide) 2025: Prostate Cancer Guide
Prostate Cancer and the PSA Test: Key Facts Every Man Should Know
