News|Articles|April 6, 2026

Diabetes Drug Metformin May Mimic Exercise Benefits in Prostate Cancer

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Key Takeaways

Androgen-directed therapies can precipitate weight gain, insulin resistance, and cardiovascular risk, creating a clinical need for metabolic support when fatigue, pain, or toxicity limits exercise capacity.
Elevations in Lac-Phe with metformin mirrored post-exertional physiology and were maintained after hormone therapy initiation, supporting Lac-Phe as a candidate biomarker of treatment-era metabolic adaptation.
Lack of association between Lac-Phe and PSA kinetics suggests Lac-Phe reflects systemic energy balance rather than tumor response, reframing endpoints toward tolerability and long-term comorbidity mitigation.
Divergent relationships of Lac-Phe and metformin-induced GDF-15 with weight change indicate multiple metabolic pathways may be engaged, with Lac-Phe potentially offering greater specificity for weight-related effects.
Similar Lac-Phe increases seen with other metabolic therapies imply a broader class effect on exercise-associated metabolites, warranting mechanistic and prospective clinical validation.

Diabetes drug metformin may mimic exercise effects in prostate cancer, supporting weight, metabolism and overall health during treatment.

Researchers at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine reported in EMBO Molecular Medicine that metformin increased levels of a molecule associated with exercise in patients with prostate cancer, helping scientists better understand how metabolic health may be supported during treatment.

Why this matters for patients with prostate cancer

Many patients with prostate cancer receive hormone-based therapies. While these treatments are important, they can disrupt metabolism and contribute to weight gain, insulin resistance and increased cardiovascular risk. These changes can affect energy levels, daily well-being and long-term health.

Exercise can help regulate weight, blood sugar and heart health, but fatigue, pain, advanced disease and treatment side effects often make regular activity difficult. This study matters because it explores whether some of the biological signals usually activated by exercise can also be triggered by medication, potentially supporting patients’ metabolic health when activity is limited.

What researchers found about Metformin and an exercise related molecule

Investigators focused on a molecule called N-lactoyl-phenylalanine, or Lac-Phe. This molecule is produced when lactate, which builds up during activity, combines with phenylalanine, a protein building block.

Previous research shows Lac-Phe rises after intense exercise and is associated with appetite regulation and weight control. In this study, patients treated with metformin had increased Lac-Phe levels, similar to levels seen after strenuous exercise. Importantly, patients were not exercising when blood was collected, and the effect continued after hormone therapy began.

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

Higher Lac-Phe levels were not linked to prostate-specific antigen changes, meaning the molecule does not appear to affect tumor response. Instead, it reflects how the body manages energy, weight and metabolic strain during treatment, which can affect daily life and long-term health.

Researchers also compared Lac-Phe with growth differentiation factor 15, or GDF-15, a stress hormone that rises with metformin. Lac-Phe was more closely tied to weight changes, suggesting metformin influences metabolism through multiple pathways.

“Metabolism is involved in everything cells do,” said Dr. David Lombard, 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.”

Trial details

The study was led by Drs. Priyamvada Rai, Bilusic and Lombard and included collaboration across Sylvester’s Tumor Biology, Cancer Epigenetics and Translational and Clinical Oncology programs.

Researchers evaluated blood samples from patients receiving metformin and other metabolic therapies, measuring Lac-Phe levels and comparing them with prostate-specific antigen changes. While Lac-Phe increased, it was not linked to tumor response. Similar rises were seen in patients receiving other metabolic therapies, suggesting Lac-Phe may reflect a broader metabolic response.

Safety

The press release did not report side effects associated with metformin in this study.

Researchers emphasized that metformin is not a replacement for exercise. Instead, the study highlights a way to support metabolic health, which can influence how patients feel and tolerate treatment.

“Cancer therapy often affects the body in ways that go beyond the tumor,” said Dr. Priyamvada Rai, 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.”

References

“How a Diabetes Drug May Echo the Benefits of Exercise in Prostate Cancer Care” by Monica Smith, InventUM (University of Miami Miller School of Medicine).

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