EMBO Mol Med
Metformin limits prostate cancer therapy weight gain via exercise-like pathway
Clinical takeaway: Consider metformin’s potential metabolic benefits in prostate cancer patients on hormone therapy who cannot maintain activity to support weight management.
A small study addressed a common clinical challenge: patients on anti-androgen therapy often develop weight gain and metabolic dysfunction while being less able to exercise. Investigators found that metformin may activate an exercise-linked metabolic pathway even in inactive patients.
Metformin consistently increased N-lactoyl-phenylalanine (Lac-Phe) across cohorts to levels comparable to those reported after strenuous exercise. Metformin recipients also demonstrated better weight control during hormone therapy, with most avoiding treatment-related weight gain. Lac-Phe levels didn't correlate with PSA changes or anticancer response.
These findings support prior research that suggests metformin engages a pathway tied to appetite and energy regulation that is typically seen with exercise. The effect appears independent of tumor response and may be distinct from other pathways such as GDF-15.
“From a clinical standpoint, seeing a metabolic signal that mirrors what we associate with intense exercise was striking,” said researcher and first author Marijo Bilusic, M.D., Ph.D., genitourinary medical oncologist and professor of medicine and medical oncology at the Sylvester Comprehensive Cancer Center at the University of Miami. “For patients whose treatments or symptoms limit physical activity, that kind of effect could be especially meaningful.”
Source: Bilusic M, et al. EMBO Molecular Medicine. April 6, 2026. The anti-obesogenic metabolite, Lac-Phe, is elevated by metformin treatment in prostate cancer patients