- A common diabetes drug may mimic one key effect of exercise in those with prostate cancer.
- Researchers found metformin boosts an “exercise molecule” linked to appetite and weight control, even in those unable to stay active.
- While not a substitute for exercise, the drug could help individuals manage treatment-related weight gain and metabolic health.
Regular exercise is associated with a wide range of health benefits, including a reduced risk of cancer.
Physical activity is also important during the treatment of certain cancers, such as prostate cancer, where treatment itself may lead to weight gain or other metabolic dysfunction.
Scientists previously identified an exercise-induced molecule — known as N-lactoyl-phenylalanine (Lac-Phe), a compound released during physical activity — associated with weight loss and decreased appetite, and it appears to be stimulated by metformin, a diabetes drug.
In an exploratory study, researchers found that prostate cancer patients treated with metformin had Lac-Phe levels comparable to those seen after strenuous exercise. The findings were published on April 6 in the journal EMBO Molecular Medicine.
Researchers
“Altered metabolism is one of the hallmarks of cancer. So, what would happen with cancer patients treated with metformin?” said first study author Marijo Bilusic, MD, PhD, a genitourinary medical oncologist at Sylvester Comprehensive Cancer Center.
“In our study, 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.
While metformin did not predict improved treatment response, such as PSA levels or tumor growth, it was associated with improved weight management, including among patients prescribed anti-androgen therapy, which is linked with weight gain.
S. Adam Ramin, MD, board certified urologist, urologic oncologist, and medical director of Urology Cancer Specialists in Los Angeles, CA, who wasn’t involved in the research, called it “an intriguing preliminary study,” but cautioned that larger studies would be necessary to validate the findings.
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 individuals treated at a cancer center.
In the trial, 12 patients with overweight or obesity (but not diabetes) were studied in detail out of 29 originally enrolled in the cohort. 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 an additional 25 individuals with prostate cancer across a range of disease stages, including advanced cancer. Of these, seven were taking metformin. Across both groups, the team measured Lac-Phe levels and compared them before and after treatment.
The researchers found that metformin consistently increased levels of Lac-Phe in prostate cancer, 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 participant 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 levels of Lac-Phe in the body, 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. And higher Lac-Phe levels did not predict whether a person’s cancer responded to treatment. The study builds on the findings of the
“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 importance of exercise after a prostate cancer diagnosis cannot be overstated.
Research suggests that staying physically active is associated with a roughly one-third reduction in cancer-related mortality and nearly a one-half reduction in all-cause mortality.
It is too early to predict the role metformin and, by extension, 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 pharmacological intervention 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 doesn’t act on the body in the same way, nor does it have the same spectrum 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.”
