Q&A: Phenotype test predicting semaglutide response could ‘change conversation’ on obesity
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In a Healio exclusive, Andres J. Acosta, MD, PhD, highlights data demonstrating that the MyPhenome test may serve as a biomarker to determine whether a patient with obesity will be a “good responder” to semaglutide.
Developed at the Mayo Clinic, the test stratifies patients with obesity into one of four phenotype groups to identify the optimal intervention for weight loss: hungry brain (consuming too many calories without feeling full), hungry gut (feeling hungry shortly after eating), emotional hunger (eating in response to emotional triggers) or slow burn (ineffectively burning calories).
“We have been working for over a decade on trying to predict who are the best responders for different obesity interventions,” Acosta, associate professor of medicine and consultant in the division of gastroenterology and hepatology at the Mayo Clinic, told Healio. “Our previous study told us that this phenotype called ‘hungry gut’ can identify the best responders for GLP-1s, but most of our studies were done with exenatide and liraglutide. The big question was whether our hungry gut test could predict response to semaglutide.”
Using a multicenter biobank and registry of patients who underwent weight loss interventions at the Mayo Clinic, Acosta and colleagues enrolled 84 patients (mean age, 47.6 years; mean BMI, 38.8 kg/m²) with obesity who were prescribed semaglutide 0.25 mg to 2.4 mg (Ozempic, Wegovy; Novo Nordisk).
Researchers conducted genetic studies on participant saliva and blood samples to create a machine-learning gene risk score (ML-GRS), which they stratified into hungry gut positive (ML-GRS < 0.5) and hungry gut negative (ML-GRS 0.5).
The primary endpoints were total body weight loss at 3, 6, 9 and 12 months and the probability of the ML-GRS to predict semaglutide response, defined by total body weight loss of at least 5% at 12 months.
In this Healio interview, Acosta details the study findings presented at Digestive Disease Week, how the genetic test can inform patient care and how it can be used in precision medicine to better treat patients with obesity.
Healio: How does the MyPhenome test work?
Acosta: MyPhenome (Phenomix Sciences) is a genetic test that includes approximately 6,000 single nucleotide polymorphisms. The genetic risk score is combined with different algorithms to predict whether patients have either the hungry gut phenotype, hungry brain phenotype or emotional hunger phenotype.
Healio: Can you briefly describe the study?
Acosta: This study was led by Maria Daniela Hurtado, MD, PhD, an endocrinologist at the Mayo Clinic in Florida. With her team, Hurtado created a registry in which patients who were treated with semaglutide were invited to participate and a genetic sample was obtained from them. The patients were followed for more than 1 year.
The goal was to identify who were the best responders to semaglutide because not all the patients treated with this medication have a response.
Healio: What were some significant findings from the study?
Acosta: Based on the genetic test, the key finding was that patients treated with semaglutide lost 19% of their total body weight if they were hungry gut positive compared with 10% weight loss in those who were hungry gut negative.
Healio: How do these results inform patient care?
Acosta: In patients who consider using GLP-1s, this test can help decide whether or not they are going to be a good responder, and if they need to make financial decisions such as paying for the medication out of pocket or even starting with medications.
The good thing is that even if patients are hungry gut negative, they may still be a good responder for medications for other phenotypes, [which would be] more cost-effective than semaglutide.
Healio: How can physicians use the test to speak to patients about GLP-1s?
Acosta: With the same reason patients will benefit knowing that they will respond better, it is easier for the physician to say to a patient that they are more likely going to do well with semaglutide instead of using trial and error.
It also helps physicians change the conversation about obesity. Physicians are able to tell patients that they can start and stay on GLP-1s because they have the hungry gut phenotype that likely has a strong genetic predisposition. And, with that strong genetic disposition, physicians can tell patients that they’re going to benefit from the medication for a long period of time.
Hopefully, it may solve the problem that we are seeing where the majority of patients do not stay on these medications for more than 3 months.
Healio: What does the study demonstrate on the use of precision medicine in patients with obesity?
Acosta: We are bringing precision medicine to the frontline in obesity care. Like with any other disease, we think we also need to find diagnostic tests that can improve accuracy in treating obesity, not only for patients to do better but also to make obesity treatment cost-effective.
Healio: What is the next step in research?
Acosta: The study only includes a little more than 80 patients, so, we need to do studies in a larger population that is more diverse. Ideally, these medications should be studied in multicentered, randomized placebo-controlled trials.
References:
- Fansa S, et al. Performance of a machine-learning gene risk score biomarker on predicting response to semaglutide: A prospectively followed multicenter biobank and outcomes registry. Presented at: Digestive Disease Week; May 18-21, 2024; Washington (hybrid).
- The four types of obesity. https://www.phenomixsciences.com/patients/four-types-obesity. Accessed June 27, 2024.
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