Scientists have discovered that metformin, a widely prescribed diabetes drug, can have benefits similar to those of regular exercise in prostate cancer patients, whose movement may be limited by their condition or treatment. Published today in EMBO Molecular Medicine, their findings show that metformin increased levels of N-lactoyl-phenylalanine (Lac-Phe), a molecule naturally produced by the body after intense exercise.
Exercise can significantly benefit prostate cancer patients both during and after treatment. These patients often receive hormone therapy, which can disrupt metabolism, contribute to weight gain, increase insulin resistance, and affect their overall cardiovascular health. While physical activity is key to supporting their recovery and addressing these side effects, fatigue, pain, and other common symptoms can limit the ability of prostate cancer patients to regularly exercise.
“Cancer therapy often affects the body in ways that go beyond the tumor,” said Priyamvada Rai, PhD, professor of radiation oncology and co-leader of the Tumor Biology Program at Sylvester Comprehensive Cancer Center in the University of Miami Miller School of Medicine. “Supporting metabolic health can influence how patients tolerate treatment and how they feel over time, even if it doesn’t directly change tumor growth. This study was an opportunity to investigate molecular pathways that can be therapeutically activated for better outcomes to treatments that induce metabolic stress.”
Rai and colleagues found that metformin raises levels of Lac-Phe in prostate cancer patients, even in the absence of physical activity. Known for its role in regulating energy levels and weight gain, Lac-Phe is formed by combining lactate, a molecule produced during muscle contraction, and the amino acid phenylalanine. Previous preclinical and clinical studies have reported levels of Lac-Phe spiking after intense exercise and linked it to a reduction in appetite and improved weight control.
“Metabolism is involved in everything cells do,” said David B. Lombard, MD, PhD, professor of pathology and laboratory medicine and co-leader of the Cancer Epigenetics Program at the Miller School. “These findings suggest Lac-Phe may be a very informative signal for understanding how metformin affects metabolism in prostate cancer patients.”
Prostate cancer patients treated with metformin were found to produce similar levels of Lac-Phe compared to levels reported after intense exercise in previous studies of healthy volunteers. The benefits of Lac-Phe persisted even after hormone therapy began.
“From a clinical standpoint, seeing a metabolic signal that mirrors what we associate with intense exercise was striking,” said Marijo Bilusic, MD, PhD, genitourinary medical oncologist and professor of medicine and medical oncology at the Miller School. “The result isn’t a new cancer biomarker, but a clearer understanding of how a widely used drug may support metabolic health during prostate cancer treatment—an outcome that matters to patients and clinicians alike.”
Although a drug like metformin can never fully replace physical activity, these findings offer an alternative approach to accessing some of the benefits of exercise in patients with limited ability to engage in it.
“What’s encouraging about this work is that it reminds us cancer care isn’t only about targeting tumors—it’s also about supporting the whole patient,” said Rai. “By better understanding how treatments affect metabolism, we can begin to identify ways to help patients maintain strength, resilience, and quality of life throughout their care.”
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