Facsimile Metformin Prescription

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💡What To Know:

  • Metformin produced an “anti-hunger” molecule called lac-phe.
  • The diabetes drug produced more of this molecule than vigorous exercise.
  • Roughly 150 million people reportedly take metformin for diabetes worldwide.

STANFORD, Calif. — A common diabetes drug may pave the way for new weight loss treatments. Researchers from Stanford Medicine and Harvard Medical School have revealed that the moderate weight loss associated with the diabetes medication metformin is due to an “anti-hunger” molecule, known as lac-phe, which is also produced after vigorous exercise.

Metformin is widely prescribed to manage blood sugar levels in people with diabetes and has been noted to cause a slight reduction in weight.

“Until now, the way metformin, which is prescribed to control blood sugar levels, also brings about weight loss has been unclear,” says study co-senior author Dr. Jonathan Long, an assistant professor of pathology at Stanford Medicine, in a media release. “Now we know that it is acting through the same pathway as vigorous exercise to reduce hunger. Understanding how these pathways are controlled may lead to viable strategies to lower body mass and improve health in millions of people.”

Lac-phe was discovered by Stanford researchers in 2022 during their search for molecules that reduce hunger following intense physical activity. This molecule, a combination of lactate (a fatigue byproduct from muscles) and the amino acid phenylalanine, was found to suppress appetite not only in humans but also in mice and racehorses after strenuous exercise.

The study, published in the journal Nature Metabolism and funded by the National Institutes of Health, found that obese mice given metformin showed elevated levels of lac-phe in their blood, leading to reduced food intake and weight loss over nine days. This was mirrored in humans with Type 2 diabetes, who exhibited increased lac-phe levels after starting metformin treatment.

The effect of metformin on lac-phe production was comparable to, if not greater than, the effects seen with exercise. This raises intriguing questions about the gut-to-brain communication pathways involved in hunger and metabolism and points to the potential for new oral medications targeting these pathways for weight management and health improvement.

intense workout exercise
The effect of metformin on lac-phe production was comparable to, if not greater than, the effects seen with exercise. (Credit: Julia Larson on Pexels)

“There is an intimate connection between lac-phe production and lactate generation,” notes Dr. Long. “Once we understood this relationship, we started to think about other aspects of lactate metabolism.”

Dr. Long’s team also discovered that intestinal epithelial cells produce lac-phe, suggesting a complex interplay between the gut and metabolic regulation. Blocking the production of lac-phe in mice nullified the appetite-suppressing and weight-reducing effects of metformin, underscoring the molecule’s crucial role.

“It was nice to confirm our hunch experimentally,” says Dr. Long. “The magnitude of effect of metformin on lac-phe production in mice was as great as or greater than what we previously observed with exercise. If you give a mouse metformin at levels comparable to what we prescribe for humans, their lac-phe levels go through the roof and stay high for many hours.”

The study not only confirms the link between metformin use, lac-phe production, and weight loss but also opens the door to developing new classes of weight loss drugs that could mimic these effects without the need for injections, unlike current treatments like semaglutide (e.g., Ozempic and Wegovy).

“These findings suggest there may be a way to optimize oral medications to affect these hunger and energy balance pathways to control body weight, cholesterol and blood pressure,” concludes Dr. Long. “I think what we’re seeing now is just the beginning of new types of weight loss drugs.”

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