Best Repurposed Medication for Prostate Cancer
The evidence does not support any repurposed medication as standard treatment for prostate cancer, including metformin, which showed no overall survival benefit in the largest and most recent randomized trial. 1
Current Evidence on Metformin
Definitive Trial Results
The STAMPEDE trial (2025), the highest-quality evidence available, definitively tested metformin in 1,874 patients with metastatic hormone-sensitive prostate cancer. This trial found no significant improvement in overall survival (HR 0.91,95% CI 0.80-1.03; p=0.15), with median survival of 67.4 months in the metformin group versus 61.8 months in standard care. 1
Key findings from STAMPEDE:
- No survival benefit in the overall population of metastatic prostate cancer patients 1
- Metformin did reduce adverse metabolic side-effects of androgen deprivation therapy (ADT) 1
- Side effects were primarily gastrointestinal (9% grade 3+ events versus 7% in control) 1
Contradictory Earlier Evidence
A smaller Egyptian trial (MANSMED, 2021) with 124 patients suggested benefit, showing improved castration-resistant prostate cancer-free survival (29 vs 20 months, p=0.01). 2 However, this contradicts the larger, more recent STAMPEDE trial and should not guide practice. The MANSMED trial had significant limitations including smaller sample size and shorter follow-up (22 months median). 2
Why Metformin Fails as Repurposed Therapy
Despite preclinical studies showing antineoplastic effects through various molecular mechanisms 3, and early studies suggesting benefits in inhibiting cancer cell proliferation 3, the definitive phase 3 trial demonstrates these laboratory findings do not translate to survival benefit in real-world clinical practice. 1
Standard of Care Remains Unchanged
Current guidelines do not recommend any repurposed medications for prostate cancer treatment. 4
For metastatic hormone-sensitive prostate cancer, evidence-based options include:
- ADT plus docetaxel for fit patients with high-volume disease 4
- ADT plus novel hormone agents (abiraterone, enzalutamide, apalutamide, or darolutamide) 4
- Triplet therapy (ADT + docetaxel + abiraterone or darolutamide) for fit patients with de novo metastatic disease 4
For castration-resistant prostate cancer:
- Abiraterone or enzalutamide for chemotherapy-naïve patients 4
- Olaparib for patients with BRCA1/2 alterations after androgen receptor axis inhibitors 4
- 177Lu-PSMA-617 for patients with PSMA-expressing tumors after taxane and novel androgen receptor axis inhibitor 4
Clinical Bottom Line
There is no repurposed medication that should be recommended for prostate cancer treatment based on current evidence. 1 While metformin may help mitigate metabolic complications of ADT 1, this does not justify its use as an anticancer agent given the lack of survival benefit. Patients should receive guideline-concordant therapy with proven survival benefits rather than repurposed medications. 4