A recent article in The Lancet reviewed the impact of metformin on prostate cancer patients, focusing primarily on findings from the STAMPEDE trial and offering some noteworthy insights.

The STAMPEDE trial, a large-scale study involving 1,874 non-diabetic patients with metastatic hormone-sensitive prostate cancer (mHSPC), explored the metabolic effects of adding metformin to standard treatments, which included androgen deprivation therapy (ADT) with or without radiotherapy, docetaxel, or androgen receptor pathway inhibitors (ARPI). Patients were divided evenly into two groups: one receiving standard care alone and the other receiving standard care plus metformin at a target dose of 850 mg twice daily. The trial, conducted over a median follow-up of 60 months, primarily aimed to assess overall survival but also evaluated metabolic parameters, toxicity, and various survival metrics.

The results showed that metformin did not improve overall survival, with patients in the metformin group living a median of 67.4 months compared to 61.8 months for those on standard care alone, a difference that was not statistically significant. Similarly, other survival outcomes—such as prostate cancer-specific survival, progression-free survival, metastatic progression-free survival, and failure-free survival—showed no notable differences between the groups.

However, metformin had a significant impact on metabolic health. After 104 weeks, patients taking metformin experienced less weight gain, lower fasting glucose levels, reduced total cholesterol, lower LDL cholesterol, decreased glycated hemoglobin (HbA1c), and smaller waist measurements compared to those on standard care alone.
These metabolic benefits are particularly relevant because ADT, a mainstay of mHSPC treatment, often leads to side effects like reduced insulin sensitivity, dyslipidemia, weight gain, and increased cardiovascular risk. The trial’s patient breakdown included 15% on ADT alone, 82% on ADT plus docetaxel, and 3% on ADT plus ARPI, reflecting treatment practices at the time. A key limitation is that most patients received docetaxel rather than ARPI, which has since become the preferred standard, potentially limiting how applicable the findings are today. Additionally, most participants had newly diagnosed disease, which may not fully represent the broader mHSPC population. The metabolic improvements are meaningful, especially as data suggest that about 25% of deaths in mHSPC patients occurring more than 5 years after diagnosis are due to non-cancer causes, with cardiovascular disease playing a significant role. While metformin did not extend life expectancy, its ability to counteract ADT-related metabolic issues suggests it could improve quality of life and cardiometabolic health. Questions remain about whether metformin should be recommended for all patients on ADT or only those with pre-existing metabolic conditions, and whether these benefits reduce cardiovascular complications.

As mHSPC survival continues to improve, managing long-term side effects and comorbidities will likely become a greater focus, with metformin potentially playing a role in future treatment strategies.

Source.