Hundreds of millions of people around the world are affected by obesity, which is caused by a number of influences including habits, genetics, and environmental factors, which may vary significantly from one person to another. Recently developed weight loss medications known as GLP1 RAs are helping people lose weight, but not everyone responds the same way to the drugs. Now scientists have found that a genetic test can predict how a patient will respond to GLP1 RAs. The findings have been reported in Cell Metabolism.
This novel test can measure how many calories a person has to consume to feel full (satiety), a metric known as calories to satiation (CTS).
"Patients deserve treatments that reflect their biology, not just their body size," noted senior study author Andres Acosta, MD, PhD, a gastroenterologist at Mayo Clinic. "This test helps us deliver the right medication to the right person from the start."
Previous work by Acosta and colleagues developed categories of eating patterns in obesity, or obesity phenotypes. These include categories like ‘hungry brain,’ in which obese individuals tend to have large meals, or ‘hungry gut,’ in which obese individuals usually eat average-sized portions but tend to eat more often.
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In this work, the investigators assessed satiety, when the body feels it has had enough food. About 800 obese volunteers were recruited for a satiety study. They were asked to eat as much lasagna, pudding, and milk as it took for them to feel “Thanksgiving full.”
This study showed that some people stopped eating once they’d consumed 140 calories. But others ate more than 2,000. Men also tended to eat more than women. When the scientists began to consider why there was so much variability, they looked at a number of factors. Some factors were contributing, but none of them fully explained that variation. So the scientists next assessed the genetics of the study volunteers.
The investigators focused on ten genes that have a known effect on food intake. They developed a test to measure CTS-GRS (Calories to Satiation Genetic Risk Score), which can be done with DNA from a saliva or blood sample.
The CTS-GRS was applied to the results of clinical trials of two GLP1-RAs. This assessment showed that those with a higher score lost more weight on a phentermine-topiramate drug, which may help reduce the intake of large meals.
Meanwhile, the drug liraglutide was better for those with a lower score, and it could be helping people eat less throughout the day. Now, the team is applying this approach to other GLP1 RAs Ozempic and Wegovy, and these results should be available soon.
"With one genetic test, we can predict who is most likely to succeed on two different medications," said Acosta. "That means more cost-effective care and better outcomes for patients."
Sources: Mayo Clinic, Cell Metabolism