Graphical summary. Credit score: Cell Metabolism (2025). DOI: 10.1016/j.cmet.2025.05.008
Mayo Clinic researchers have developed a genetic take a look at that may assist predict how individuals will reply to weight reduction drugs similar to GLP-1s.
The take a look at estimates a person’s energy to satiation (CTS)—how a lot meals it takes for an individual to really feel full—and hyperlinks this organic trait to therapy success. The findings, printed in Cell Metabolism, symbolize a promising step towards extra customized and efficient therapies for individuals residing with weight problems.
“Patients deserve treatments that reflect their biology, not just their body size,” says Andres Acosta, M.D., Ph.D., a gastroenterologist at Mayo Clinic and senior writer of the examine. “This test helps us deliver the right medication to the right person from the start.”
Past physique measurement
Weight problems is a power, advanced illness that impacts greater than 650 million adults worldwide. It stems from a mixture of genetic, environmental and behavioral elements that modify from individual to individual. This complexity helps clarify why individuals reply otherwise to weight-loss interventions. But therapy selections usually depend on easy measures similar to physique mass index (BMI) fairly than the organic processes that drive weight achieve and weight reduction.
To uncover these processes, Dr. Acosta has centered on satiation, the physiological sign that tells the physique it has eaten sufficient. In 2021, he and his colleagues outlined a sequence of weight problems phenotypes to explain consuming patterns. For instance, some individuals with weight problems are inclined to eat very massive meals (“hungry brain”), whereas others might eat common parts however snack often all through the day (“hungry gut”).
On this examine, the researchers studied satiation in almost 800 adults with weight problems by inviting them to partake in an all-you-can-eat meal of lasagna, pudding and milk till they felt “Thanksgiving full.” The outcomes revealed hanging variation: Some contributors stopped after 140 energy whereas others consumed greater than 2,000. On common, males consumed extra energy than ladies.
The workforce investigated potential explanations for this variability. A number of elements, together with physique weight, top, proportion of physique fats, waist-to-hip ratio and age—in addition to appetite-related hormones similar to ghrelin and leptin—performed a small function. However none accounted for the large vary in calorie consumption. So the researchers turned to genetics.
Utilizing machine studying, the researchers mixed variants in 10 genes recognized to affect meals consumption right into a single metric known as the CTS-GRS (Energy to Satiation Genetic Threat Rating). The rating, calculated from a blood or saliva pattern, offers a customized estimate of an individual’s anticipated satiation threshold.
Matching genes to drugs
Mayo Clinic researchers then calculated this CTS-GRS metric in scientific trials of two FDA-approved drugs: a first-generation weight reduction drug, phentermine-topiramate (model title Qsymia), and a more moderen GLP-1 drug, liraglutide (Saxenda). They discovered that:
Folks with a excessive satiation threshold misplaced extra weight on phentermine-topiramate. This drug might assist management portion measurement and scale back large-meal overeating (hungry mind).
Folks with a low satiation threshold responded higher to liraglutide. This drug might scale back total starvation and frequency of consuming (hungry intestine).
“With one genetic test, we can predict who is most likely to succeed on two different medications,” says Dr. Acosta. “That means more cost-effective care and better outcomes for patients.”
The workforce has performed extra research to foretell response to semaglutide, one other GLP-1 remedy (bought below the model names Ozempic and Wegovy), and outcomes are anticipated quickly.
They’re working to broaden the take a look at by incorporating knowledge from the microbiome and metabolome, in addition to creating fashions to foretell widespread unwanted effects similar to nausea and vomiting.
Extra info:
Lizeth Cifuentes et al, Genetic and physiological insights into satiation variability predict responses to weight problems therapy, Cell Metabolism (2025). DOI: 10.1016/j.cmet.2025.05.008
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