Metformin May Mimic Exercise Signals in Prostate Cancer Care

Exercise remains one of the most effective ways to support overall health during cancer treatment, helping regulate weight, blood sugar and cardiovascular function. However, for many patients with cancer, maintaining regular physical activity is not always possible due to fatigue, pain, hormone therapy or advanced disease.

New research suggests that a commonly used diabetes medication may help activate some of the same biological pathways associated with exercise, offering a potential way to support metabolic health when physical activity is limited.

Investigators 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 naturally occurring molecule tied to energy balance and weight regulation in patients with prostate cancer.

The findings do not suggest that medication can replace exercise. Instead, they provide insight into how the body processes metabolic signals and how those signals might be supported during treatment.

Understanding an Exercise-Linked Molecule

The study focused on a molecule known as N-lactoyl-phenylalanine, or Lac-Phe. This compound forms when lactate, which builds up during physical exertion, combines with phenylalanine, an amino acid involved in protein production.

Researchers have observed that Lac-Phe levels rise significantly after intense exercise and are associated with appetite regulation and weight control. These effects are often seen in individuals who engage in regular physical activity.

In this study, investigators found that Lac-Phe levels also increased in patients taking metformin, even when they were not exercising. The levels measured were similar to those previously reported after strenuous physical activity.

This observation raised an important question for cancer care: whether metabolic pathways typically activated by exercise could also be triggered through medication in patients unable to stay active.

Examining Metabolism in Prostate Cancer

The research team focused on patients with prostate cancer, particularly because hormone-based treatments commonly used in this disease can disrupt metabolism. These therapies are associated with weight gain, insulin resistance and increased cardiovascular risk.

Among patients receiving metformin, Lac-Phe levels rose and remained elevated even after hormone therapy began. However, the increase in Lac-Phe was not linked to tumor response. Researchers found no association between the molecule and changes in prostate-specific antigen levels, a standard marker used to monitor prostate cancer.

This distinction highlights the role of Lac-Phe as a marker of metabolic activity rather than a direct indicator of cancer control.

The study findings were also consistent across different treatment settings, with similar increases observed in patients receiving other metabolic therapies. This suggests that Lac-Phe may reflect a broader response to metabolic stress rather than an effect unique to metformin.

Comparing Metabolic Pathways

Metformin is known to increase levels of GDF-15, a hormone associated with stress and appetite regulation. However, researchers found that Lac-Phe was more closely linked to weight-related changes in patients.

Because the two molecules did not rise in parallel, the findings suggest that metformin may influence metabolism through multiple pathways, with Lac-Phe playing a distinct role in weight regulation.

Researchers noted that understanding these pathways could help clinicians better manage treatment-related metabolic changes, which can affect how patients tolerate therapy.

Implications for Patient Care

While additional research is needed, the study offers a clearer view of how metabolic health can be supported during cancer treatment.

Cancer therapies often affect more than the tumor, influencing how patients feel physically and how well they tolerate treatment. Identifying ways to support metabolism may help improve quality of life, even if those strategies do not directly impact tumor growth.

The findings also reinforce the importance of a whole-patient approach to cancer care. For patients who are unable to exercise regularly, understanding how medications like metformin interact with metabolic pathways may provide new opportunities to maintain strength and resilience during treatment.

Researchers emphasized that exercise remains an important component of care when possible. However, studies like this may help expand options for supporting patients whose circumstances limit physical activity, offering additional tools to address the metabolic challenges that can arise during prostate cancer treatment.

Reference

Smith M. How a diabetes drug may echo the benefits of exercise in prostate cancer care. University of Miami Miller School of Medicine News. Published April 6, 2026. Accessed April 6, 2026.