Metformin May Mimic Exercise’s Weight-Control Benefits in Prostate Cancer Patients

A common diabetes drug may produce one key exercise-related benefit for people with prostate cancer.

Researchers discovered that metformin raises levels of an “exercise molecule” tied to appetite and weight management, even in patients who cannot stay physically active. While the drug is not a replacement for exercise, it might help patients manage weight gain and metabolic issues caused by cancer treatment.

Regular exercise offers many health advantages, including a lower risk of cancer. Physical activity also plays an important role during treatment for certain cancers, such as prostate cancer, where therapy can lead to weight gain or other metabolic problems.

Scientists had already identified a molecule called N-lactoyl-phenylalanine (Lac-Phe) that the body releases during exercise. This compound is linked to weight loss and reduced appetite. It now appears that metformin, a diabetes medication, also triggers this molecule.

In a small study, researchers found that prostate cancer patients taking metformin had Lac-Phe levels similar to those seen after intense exercise. The results were published April 6 in the journal EMBO Molecular Medicine.

Scientists first discovered Lac-Phe in healthy people and athletes, including ultramarathon runners. They later found high levels of the molecule in people with diabetes who were taking metformin.

“Altered metabolism is one of the hallmarks of cancer. So, what would happen with cancer patients treated with metformin?” said study author Dr. Marijo Bilusic, a genitourinary medical oncologist at Sylvester Comprehensive Cancer Center.

“We were very surprised to see that the level of Lac-Phe in our prostate cancer patients was exactly the same as the level of ultramarathoners. This has never been reported before,” he told Healthline.

Metformin did not predict better treatment results, such as PSA levels or tumor growth. However, it was linked to better weight control, even in patients taking anti-androgen therapy, a treatment known to cause weight gain.

Dr. S. Adam Ramin, a board-certified urologist and urologic oncologist not involved in the research, called it “an intriguing preliminary study.” He cautioned that larger studies are needed to confirm the findings.

Metformin aids weight and metabolic health in prostate cancer

Bilusic and his team analyzed blood samples from men with prostate cancer enrolled in a clinical trial called BIMET-1, along with an additional group of patients treated at a cancer center.

In the trial, researchers studied 12 overweight or obese patients (who did not have diabetes) in detail out of 29 originally enrolled. Participants were randomly assigned to receive either standard care alone or metformin at a dose of 1,000 mg twice daily, followed by combination treatment with the hormone therapy drug bicalutamide.

To confirm their findings, the researchers also studied 25 additional men with prostate cancer at various disease stages, including advanced cancer. Seven of these men were taking metformin. Across both groups, the team measured Lac-Phe levels before and after treatment.

The researchers found that metformin consistently raised Lac-Phe levels in prostate cancer patients, regardless of cancer stage, body weight, or other treatments. In the clinical trial group, Lac-Phe levels rose significantly after metformin treatment. In the broader group, those taking metformin clearly had higher levels than those who were not. The increases reached ranges similar to those seen after intense exercise.

Importantly, people taking metformin also showed better weight control during hormone therapy, which is known to cause weight gain. In the trial, nearly all individuals on metformin avoided weight gain over several months of treatment, while those not taking it were more likely to gain weight. Although not conclusive, researchers believe this may be linked to Lac-Phe levels, which are associated with reduced appetite and food intake.

While Lac-Phe is thought to act on the brain to suppress appetite, how it does so remains unclear. Higher Lac-Phe levels did not predict whether a person’s cancer responded to treatment. The study builds on findings from the STAMPEDE trial, a major study published in 2025 that found metformin improved weight management and lowered glucose levels in prostate cancer patients but showed no evidence of improved survival.

“We know that men on hormone therapy, such as oral anti-androgen therapy, tend to gain weight, develop obesity, and metabolic syndrome. Metformin may prove to be effective in preventing these complications,” said Ramin.

But, he added, “At this point, it is premature to recommend metformin to patients with prostate cancer on hormone therapy.”

The study suggests that metformin could play a supportive role in prostate cancer care by helping individuals maintain a healthier weight and potentially lowering their risk of treatment-related complications, such as heart disease.

Metformin may offer benefits, but it’s not an ‘exercise pill’

The importance of exercise after a prostate cancer diagnosis cannot be overstated. Research suggests that staying physically active is linked to roughly a one-third reduction in cancer-related death and nearly a one-half reduction in death from any cause.

It is too early to predict the role metformin and Lac-Phe might play in supporting prostate cancer treatment, but the findings are intriguing.

Because people with prostate cancer tend to be older, they may be less likely to engage in regular physical activity. A medication that could help fill that gap would represent a meaningful addition to current treatment options.

However, Bilusic cautioned that metformin is not an “exercise pill.” Exercise affects numerous systems in the body, including muscles, the cardiovascular system, neurotransmitters, and bones. Metformin does not act on the body in the same way, nor does it have the same range of effects. But in one specific pathway — increasing Lac-Phe — it appears to be meaningful.

“There are many other aspects of the exercise that metformin is probably not replacing,” Bilusic said. “But for some patients, they can’t exercise because they are in pain, [or] cancer therapy is making them fatigued. They are gaining weight. So, how can we reverse that? Taking a pill a day, that’s easier than running for a half hour in the gym.”