Weight loss by diabetes drug linked to "anti-hunger" molecule, finds study

The finding published in the journal Nature Metabolism revealed the critical role the molecule, called lac-phe, plays in metabolism, exercise and appetite which may help to discover a new class of weight loss drugs.

Many people with diabetes who are prescribed metformin lose around 2% to 3% of their body weight within the first year of starting the drug. Although this amount of weight loss is modest when compared with the 15% or more often seen by people taking semaglutide drugs, the discoveries that led to those drugs also grew from observations of relatively minor, but reproducible, weight loss in people taking first-generation versions of the medications.

“Until now, the way metformin, which is prescribed to control blood sugar levels, also brings about weight loss has been unclear,” said Jonathan Long, PhD, an assistant professor of pathology. “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.”

The researchers observed obese laboratory mice who were given metformin and found increased levels of lac-phe in their blood. They ate less than their peers and lost about 2 grams of body weight during the nine-day experiment.

In the study, Long and colleagues analyzed blood plasma samples from people with Type 2 diabetes before and 12 weeks after starting metformin treatment. They found significant increases in lac-phe levels post-metformin. Additionally, among 79 participants in a multi-ethnic atherosclerosis study taking metformin, those on the drug had higher circulating lac-phe levels compared to non-users.

Moreover, a statistical analysis of individuals in the atherosclerosis study who experienced weight loss over the study and follow-up period revealed a significant connection between metformin usage, lac-phe production, and weight reduction.

“It was nice to confirm our hunch experimentally. 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.” said Long. “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. I think what we’re seeing now is just the beginning of new types of weight loss drugs.”

Reference: Journal: Nature Metabolism