A University of Miami study finds the diabetes drug metformin can raise levels of an exercise-linked molecule in men with prostate cancer, even when they are not active. The work points to new ways to protect patients’ metabolic health during hormone therapy.
A common diabetes drug may help the body tap into one of exercise’s key biological benefits during prostate cancer treatment, even when patients are too exhausted or sick to work out.
In a new study from Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, researchers report that metformin boosts levels of a molecule tied to energy balance and weight control in men with prostate cancer. The effect appeared even when patients were inactive and continued after they started hormone-based therapy, which is known to strain metabolism.
The findings, published in the journal EMBO Molecular Medicine, suggest that metformin could help support metabolic health during treatment, a major concern for many patients on hormone therapy who struggle with fatigue, weight gain and changes in blood sugar.
The work does not claim that a pill can replace exercise. Instead, it offers a window into the internal pathways that make physical activity so powerful — and how at least one of those pathways might be triggered in other ways when movement is limited.
Sylvester researcher and first author Marijo Bilusic, a genitourinary medical oncologist and professor of medicine and medical oncology at the Miller School, noted the project depended on close collaboration between basic scientists and clinicians.
“This study reflects what’s possible when laboratory science, metabolic biology and clinical investigation are intentionally brought together for transdisciplinary studies,” Bilusic said in a news release. “By working across Sylvester’s Tumor Biology, Cancer Epigenetics and Translational and Clinical Oncology programs, we were able to link a well-defined molecular signal to real patient data. 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.”
At the center of the study is a molecule with a technical name and a straightforward role: N-lactoyl-phenylalanine, or Lac-Phe.
Lac-Phe is produced when the body is under metabolic demand. It forms when lactate — which builds up during exertion — combines with phenylalanine, an amino acid that serves as a building block of proteins. Scientists first became interested in Lac-Phe after noticing that its levels spike after intense exercise, alongside changes in appetite and how the body uses energy.
Early research in animals and humans has linked higher Lac-Phe levels with reduced appetite and better weight control, two effects commonly associated with regular physical activity.
But Lac-Phe does not rise only with exercise. Other studies have found that people taking metformin also show elevated Lac-Phe, even when they are not physically active. That overlap raised a practical question for cancer care: if a pathway usually associated with exercise can be activated by a drug, could that help patients whose treatments make it hard to move?
To explore that idea, the Sylvester team focused on prostate cancer patients receiving hormone-based therapies. These treatments lower or block male hormones that can fuel tumor growth, but they also disrupt metabolism, contributing to weight gain, insulin resistance and higher cardiovascular risk.
The researchers found that Lac-Phe levels in patients treated with metformin were similar to levels previously reported after strenuous exercise. This occurred even though the men were not exercising at the time their blood was drawn, and the increase persisted after hormone therapy began.
“From a clinical standpoint, seeing a metabolic signal that mirrors what we associate with intense exercise was striking,” Bilusic added. “For patients whose treatments or symptoms limit physical activity, that kind of effect could be especially meaningful.”
Importantly, higher Lac-Phe levels did not track with changes in prostate-specific antigen, or PSA, a standard blood marker used to monitor prostate cancer. That means Lac-Phe did not appear to reflect how well metformin was working against the tumor itself.
Instead, the molecule seemed to be a marker of how the body was handling energy, weight and metabolic stress during treatment. The researchers also saw Lac-Phe increases in patients receiving other metabolic therapies, suggesting it may be part of a broader response rather than a metformin-specific effect.
Co-corresponding author Priyamvada Rai, a co-leader of Sylvester’s Tumor Biology Program and a professor of radiation oncology at the Miller School, emphasized that distinction is crucial.
“Cancer therapy often affects the body in ways that go beyond the tumor,” Rai said in the news release. “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.”
Metformin is already known to raise levels of a stress hormone called GDF-15, which has been linked to weight loss. In this study, however, Lac-Phe was more closely tied to weight changes than GDF-15, and the two signals did not always rise together. That pattern suggests metformin may influence weight and metabolism through multiple pathways, with Lac-Phe playing a prominent role in this patient group.
Co-corresponding author David B. Lombard, a co-leader of Sylvester’s Cancer Epigenetics Program and a professor of pathology and laboratory medicine at the Miller School, underscored the broader implications.
“Metabolism is involved in everything cells do,” Lombard said. “These findings suggest Lac-Phe may be a very informative signal for understanding how metformin affects metabolism in prostate cancer patients.”
The study adds to a growing body of work showing that cancer care is not only about shrinking tumors, but also about helping patients maintain strength and quality of life during and after treatment. Hormone therapy and other systemic treatments can leave patients dealing with fatigue, muscle loss, weight gain and increased risk of diabetes and heart disease — issues that can shape long-term health and recovery.
The new findings point toward more holistic approaches, according to Rai.
“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,” she said. “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.”
The researchers emphasize that more and larger studies are needed to clarify how Lac-Phe might be used in practice — for example, as a marker to track metabolic stress, to tailor supportive therapies, or to identify patients who might benefit most from drugs like metformin during hormone therapy.
For now, the work offers a hopeful message: even when exercise is not possible, science may find new ways to tap into some of its benefits, helping patients navigate cancer treatment with more energy and resilience.