‘Hungry Gut’ Gene May Indicate Who Responds Best to Weight Loss Drugs
A “hungry gut” gene may indicate who responds best to weight loss drugs like Ozempic and Wegovy, new research finds.
“Hungry gut” refers to the type of obesity phenotype that occurs when someone eats a meal but feels hungry again after an hour or two due to their stomach emptying quickly.
An expert explains the findings.
Weight loss drugs have boomed in popularity in the last year, and many people may be wondering if these medications could work for them. (In case you didn’t know, these drugs don’t work for everyone!) Turns out, your responsiveness to drugs like Wegovy may depend on your genetics more than anything else.
A study presented at the Digestive Disease Week 2024 conference examined 84 people with obesity or other weight management issues in order to investigate how genetics plays a role in weight loss drug effectiveness. For the study, researchers developed a machine-learning gene risk score to predict “hungry gut”—the type of obesity phenotype (genetic predisposition) that occurs when someone eats a meal but feels hungry again after an hour or two due to their stomach emptying quickly.
Researchers collected saliva or blood samples from participants for genetic analysis and obtained information on eating habits. The participants took a semaglutide (generic name for Ozempic, Wegovy) medication for one year, during which the researchers recorded total body weight loss at 3, 6, 9, and 12 months. Researchers then determined the probability of a positive semaglutide response based on the type of weight management issue.
The research team at Mayo Clinic developed a test called MyPhenome that categorizes the type of obesity phenotype that can help improve weight loss. The four types were:
Hungry brain: consuming too many calories without feeling full
Hungry gut: eating a full meal but feeling hungry again soon after
Emotional hunger: eating in response to an emotional trigger
Slow burn: burning calories too slowly
The researchers reported that people who were hungry gut positive lost 14% of their body weight at 9 months, compared to 10% for those who were hungry gut negative. And after 12 months, those who were hungry gut positive lost 19% of their total body weight, while those who were hungry gut negative remained right around 10% body weight loss.
So, what does it mean to be “hungry gut positive”? Basically, a person who is “hungry gut positive” is thought to have a collection of genes that cause more rapid emptying of their stomach after a meal, so they feel hungrier sooner than others might, explains Meghan Garcia-Webb, M.D., triple board-certified in internal medicine, lifestyle medicine, and obesity medicine physician and internist at Beth Israel Lahey Health. “This is thought to be a key driver of their obesity.”
In general, it would be useful to know if someone fits this “hungry gut positive” profile, Dr. Garcia-Webb continues. “Someone whose stomach empties food faster after a meal would likely respond well to semaglutide, which slows the transit of food through the stomach, keeping a patient satisfied for longer.”
This is exactly what the study showed, she explains. Researchers found that when they sorted participants into these genetic profiles of “hungry gut positive” and “hungry gut negative,” the “hungry gut positive” patients lost significantly more weight on semaglutide than the “hungry gut negative” subjects at the 9 and 12 month markers, Dr. Garcia-Webb points out.
Identifying your own obesity phenotype could be a very useful tool in the clinical setting, says Dr. Garcia-Webb. “It can take months and months to see effects from these weight loss medications, and the paperwork to get them approved can be an additional burden. A test that can accurately predict who will be successful on particular medications can save physicians and patients a lot of time and energy,” she explains, not to mention cost!
The bottom line
Using a genetic test to identify your obesity phenotype may be an important step in weight medication management, with the goal of getting patients the right medication as soon as possible, says Dr. Garcia-Webb. “Right now, there is a lot of trial and error, and it can take several months to determine whether a weight loss medication is having the intended effect for a patient. A test like this could be a significant shortcut for patients and physicians,” she notes.
And, because this study looked at the response to semaglutide, the results can be interpreted in the context of both Wegovy and Ozempic, which are different commercial names for semaglutide, says Dr. Garcia-Webb.
Still, it’s important to acknowledge that this particular study did not limit the subjects to non-diabetic patients, or separate the groups into subjects with obesity and [type 2] diabetes, and subjects with obesity but no diabetes, says Dr. Garcia-Webb. “Also, it was a small number of patients, mostly female and Caucasian, so as the researchers point out, larger studies are needed to assess the validity of the test in a larger, more diverse population.”
Overall, Dr. Garcia-Webb says that it’s a very promising and exciting study in an area of research that “will significantly impact prescribing weight loss medications in the clinical setting.” If you have questions about whether weight loss drugs are right for you, talk to your doctor to discuss your options.
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