Exercise in a Pill? Metformin Shows Surprising Effects in Cancer Patients

Researchers have identified a surprising metabolic effect of a widely used diabetes drug in men undergoing prostate cancer treatment.

A new study suggests that metformin, a commonly prescribed drug for diabetes, may reproduce a key biological effect of exercise in men with prostate cancer. Researchers found that the medication increases levels of a molecule linked to energy balance and weight regulation, even in patients who are not physically active. The results indicate that metformin could help ease the metabolic stress caused by hormone therapy, which often reduces patients’ ability to exercise due to fatigue and other side effects.

The research was led by physician-scientists at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, and published in EMBO Molecular Medicine.

Exercise is widely recognized as a powerful way to support health during cancer treatment. It helps control body weight, stabilize blood sugar, and maintain heart health. These factors play a major role in how patients feel during therapy and how well they recover afterward.

However, many cancer patients cannot maintain a regular exercise routine. Fatigue, treatment-related side effects, pain, and advanced disease can all limit physical activity at a time when metabolic health is especially important.

That reality has led researchers to ask a practical question: if the benefits of exercise are driven by specific biological signals, could those same signals be triggered in other ways?

A Drug That Mimics Exercise Signals

The findings suggest this may be possible. Researchers at Sylvester report that metformin increases levels of a naturally occurring molecule that helps regulate how the body uses energy and manages weight in prostate cancer patients.

The study does not imply that medication can replace exercise. Instead, it sheds light on the biological pathways behind exercise-related metabolic benefits and suggests those pathways might still be activated when physical activity is limited.

“This study reflects what’s possible when laboratory science, metabolic biology and clinical investigation are intentionally brought together for transdisciplinary studies,” said Sylvester researcher and first author, Marijo Bilusic, M.D., Ph.D., genitourinary medical oncologist and professor of medicine and medical oncology at the Miller School. “By working across Sylvester’s Tumor Biology, Cancer Epigenetics and Translational & 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 called N-lactoyl-phenylalanine, or Lac-Phe. Although its name is complex, its function is relatively easy to understand.

Lac-Phe is produced when the body is under metabolic strain. It forms when lactate, which builds up during physical exertion, combines with phenylalanine, a building block of protein. Scientists first identified Lac-Phe as important because its levels rise sharply after intense exercise, alongside changes in energy use and appetite control.

Earlier laboratory and human studies have linked higher levels of Lac-Phe to reduced appetite and better weight management, both of which are commonly associated with regular exercise.

Metformin and Metabolic Pathways

Lac-Phe is not limited to exercise. Researchers have found increased levels of Lac-Phe in people taking metformin, even when they are not physically active. This overlap raised an important question for cancer care. Could a pathway normally triggered by exercise be activated with medication in patients whose treatments limit movement?

To investigate, the Sylvester team focused on prostate cancer. Hormone-based therapies used in this disease are known to disrupt metabolism, often leading to weight gain, insulin resistance, and increased cardiovascular risk.

The study showed that patients taking metformin had Lac-Phe levels similar to those seen after intense exercise. This effect was observed even though patients were not exercising when their blood was collected, and it continued after hormone therapy began.

“From a clinical standpoint, seeing a metabolic signal that mirrors what we associate with intense exercise was striking,” said Bilusic. “For patients whose treatments or symptoms limit physical activity, that kind of effect could be especially meaningful.”

Importantly, higher Lac-Phe levels were not linked to a direct anti-tumor effect. The molecule did not correlate with changes in prostate-specific antigen (PSA), a common marker used to track prostate cancer.

This distinction is key to understanding the findings. While larger studies are needed to determine whether Lac-Phe could serve as a marker of anticancer activity, current results suggest it reflects how the body handles energy, weight, and metabolic stress during treatment.

The researchers also confirmed the results in multiple clinical settings. Increases in Lac-Phe were seen in patients receiving other metabolic therapies, indicating the effect may represent a broader metabolic response rather than one specific to metformin.

“Cancer therapy often affects the body in ways that go beyond the tumor,” said Sylvester researcher Priyamvada Rai, Ph.D., co-leader, Tumor Biology Program and professor of radiation oncology at the Miller School. “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.”

Multiple Pathways at Work

Metformin is known to increase levels of a stress hormone called GDF-15. However, this study found that Lac-Phe had a stronger connection to weight changes. Because the two molecules did not rise together, the results suggest metformin affects body weight through multiple biological pathways, with Lac-Phe playing a significant role.

“Metabolism is involved in everything cells do,” said Sylvester researcher David B. Lombard, M.D., Ph.D., co-leader, Cancer Epigenetics Program and professor of pathology and laboratory medicine 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.”

Overall, the study provides new insight into how a widely used diabetes medication may help support metabolic health during prostate cancer treatment.

“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.”

Reference: “The anti-obesogenic metabolite, Lac-Phe, is elevated by metformin treatment in prostate cancer patients” by Marijo Bilusic, Durga Prasad Gannamedi, Bhipasha Challu, Shomita Ferdous, Beatriz Mateo-Victoriano, Sheela Pokharel, Defne Bayik, Janaki Sharma, David B Lombard and Priyamvada Rai, 6 April 2026, EMBO Molecular Medicine.

DOI: 10.1038/s44321-026-00408-6

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