Diabetes drug may echo benefits of exercise in prostate cancer care

A new study has found that metformin, a widely prescribed diabetes drug, may mimic one of exercise’s core biological effects in men with prostate cancer.

The findings suggest metformin could help counter the metabolic strain of hormone therapy, when fatigue and other side effects often limit physical activity.

Exercise is one of the most reliable ways to support health during cancer treatment.

It can help regulate weight, blood sugar and cardiovascular health, all of which shape how patients feel during therapy and how well they recover afterwards.

For many people with cancer, however, regular exercise is not always feasible. Fatigue, hormone therapy, pain or advanced disease can limit physical activity precisely when metabolic health becomes most important.

That has led researchers to ask whether some of exercise’s benefits, driven by specific biological signals, might be activated in other ways.

According to the research, the answer may be yes.

The study found metformin raised levels of a naturally occurring molecule involved in how the body manages energy and weight in prostate cancer patients.

The finding does not suggest that a pill can replace physical activity. Instead, it offers insight into the internal pathways behind exercise’s metabolic benefits and how they might still be engaged when movement is limited.

“This study reflects what’s possible when laboratory science, metabolic biology and clinical investigation are intentionally brought together for transdisciplinary studies,” said Marijo Bilusic, first author of the study, genitourinary medical oncologist and professor of medicine and medical oncology.

“By working across Sylvester’s Tumor Biology, Cancer Epigenetics and Translational & Clinical Oncology programmes, 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 centre of the study is a molecule called N-lactoyl-phenylalanine, or Lac-Phe. While the name is technical, its role is relatively simple.

Lac-Phe is produced when the body is under metabolic demand. It forms when lactate, a substance that builds up during exertion, combines with phenylalanine, a basic building block of protein. Scientists first took notice of Lac-Phe because its levels rise after intense exercise, alongside shifts in energy use and appetite regulation.

In preclinical and early human studies, higher Lac-Phe levels have been associated with reduced appetite and improved weight control, two effects commonly linked to regular physical activity.

Lac-Phe does not rise only with exercise. Scientists had already observed elevated Lac-Phe levels in people taking metformin, even without physical activity.

That raised an important question for cancer care: could a pathway typically associated with exercise be activated by medication in patients whose treatments limit movement?

To explore that question, the team focused on prostate cancer, where hormone-based therapies are known to disrupt metabolism, contributing to weight gain, insulin resistance and cardiovascular risk.

Lac-Phe levels in patients treated with metformin approximated those previously reported after strenuous exercise.

This happened even though patients were not exercising at the time of blood collection, and the effect persisted 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.”

Higher Lac-Phe levels were not associated with anti-tumour response to metformin. The metabolite did not correlate with changes in prostate-specific antigen, or PSA, a standard marker used to monitor prostate cancer.

While larger studies are still needed to assess whether Lac-Phe could serve as a marker of anticancer efficacy, the findings suggest it reflects how the body manages energy, weight and metabolic strain during treatment. The results were also confirmed in other settings.

Increases were seen in patients receiving other metabolic therapies, suggesting Lac-Phe may reflect a broader metabolic response rather than a drug-specific effect.

“Cancer therapy often affects the body in ways that go beyond the tumour,” said Priyamvada Rai, co-leader of the Tumor Biology Program and professor of radiation oncology.

“Supporting metabolic health can influence how patients tolerate treatment and how they feel over time, even if it doesn’t directly change tumour 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 also raises a stress hormone called GDF-15, but this study found that Lac-Phe was more closely tied to weight changes.

Because the two did not rise together, the researchers said metformin likely affects weight through multiple pathways, with Lac-Phe playing a bigger role.

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

“These findings suggest Lac-Phe may be a very informative signal for understanding how metformin affects metabolism in prostate cancer patients.”

Taken together, the findings offer a clearer picture of how a widely used diabetes medication may influence metabolic health during prostate cancer care.

“What’s encouraging about this work is that it reminds us cancer care isn’t only about targeting tumours, 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.”