May 23, 2023 – It sounds like a simple solution to a complicated problem: Find out what kind of obesity you have based on a one-time genetic saliva test. Then you and your doctor can get a better idea if anti-obesity drugs or other treatments are more likely to work for you.
The goal of creating the obesity types and test is to increase chances you’ll lose weight and improve your health and well-being, vs. a one-strategy-fits-all approach. It’s what Mayo Clinic researchers had in mind when they created four phenotypes of obesity.
Obesity experts not affiliated with the research have some concerns and say independent studies are needed to verify the potential of this strategy.
This research could help predict who will respond best to popular anti-obesity medications, said Andres Acosta, MD, PhD, co-founder of Phenomix Sciences, the company behind the tests. These medications include the class of drugs called glucagon-like peptide receptor agonists (GLP-1s) like liraglutide (Saxenda, Victoza) and semaglutide (Ozempic, Wegovy).
“We know that not everyone on a GLP-1 will respond. In reality, about a third of the patients don’t do well with GLP-1s,” said Acosta, an assistant professor of medicine and researcher in the Division of Gastroenterology and Hepatology at the Mayo Clinic in Rochester, MN.
Furthest along in development is the “My Phenome Hungry Gut” test for predicting GLP-1 response. People in this Hungry Gut group tend to empty their stomach after a meal faster and are more likely to feel hungry again a short time later, as explained on the company’s website.
A pilot study to test how well it works started in April at three primary care practices. Plans are to expand real-world testing for this and other obesity types later this year.
The other obesity categories are:
- “Hungry Brain,” where the brain does not recognize signals that the stomach is full
- “Emotional Hunger,” where cravings to eat are driven by emotions, anxiety, and negative feelings
- “Slow Burn,” where people have a slow metabolism and low energy level
People in these categories might be more likely to benefit from other obesity management strategies, like changes to their diet or placement of an intragastric balloon.
Some Things to Consider
While applauding their efforts to be more precise in treating people with obesity, not all experts are convinced this saliva test will be the answer. The company’s research might look promising, but verification of results is warranted.
“Can we get better outcomes with things like this? Well, that’s the hope,” said Jaime Almandoz, MD, medical director of Weight Wellness at the University of Texas Southwestern Medical Center in Dallas.
“We still don’t have randomized trials where we’re looking at obesity phenotyping yet,” said Almandoz, who is also a spokesperson for The Obesity Society, a professional group of clinicians, researchers, educators, and others focused on obesity science, treatment, and prevention.
There is always concern when a diagnostic test is being developed for commercial use, said Daniel Bessesen, MD, a professor of medicine-endocrinology, metabolism, and diabetes at the University of Colorado School of Medicine in Denver. “What they’re talking about doing is super important. But this is a company. This is a company that is, I think, selling a product.”
In an online search, Bessesen did not find any external studies that showed how well the saliva testing worked. But referring to work by Acosta and Michael Camilleri, MD, the other co-founder of Phenomix, he said, “I found some papers that they did that I hadn’t read before that are good.”
“These guys are smart guys. And they’ve done a lot of work on [the movement of food through the gut] and how that correlates with obesity and response to some therapies,” said Bessesen, who is also a spokesperson for The Obesity Society. “So their scientific work does line up with this area.”
Validation of any research is important because the obesity industry has been known for a lot of lose-weight-quick strategies, some with little or no science behind them, he said.
It is also essential, he said, because “anytime you do something commercial in the area of obesity, you have to acknowledge that people with obesity are a vulnerable population. These people face stigma and bias all the time.”
Removing the Stigma
If knowing your obesity type ends up making a difference, it could change the conversation people have with their medical provider, Acosta said. It could also help remove some of the stigma around obesity.
“We’re going to change the conversation because now we can say, ‘Hey, you have obesity because you have ‘Hungry Gut’ phenotype. And because of that, you’re going to respond to this medication,” Acosta said. The phenotyping suggests a strong genetic tendency – a biologic basis for obesity.
“So it’s not only a way of taking the blame out, but it’s also way of explaining that there’s a reason why you have obesity,” Acosta said. It tells people: “You’re not a failure.”
More Cost-Effective Treatment?
Targeting obesity treatment could also save on overall health care costs, Almandoz said. He estimated a cost of $1,400 per month “for forever and ever semaglutide” or at least $1,400 a month for a 3-month trial to see if this medication works in a particular person with obesity.
“That’s a lot of money when you extrapolate that out over the number of people who probably meet the criteria for treatment,” he said. A total 42% of Americans meet the CDC definition for obesity.
“You can imagine the potential cost if we were to provide anti-obesity therapies to everybody and we were to use what is the most effective class of medication, which is more than a thousand dollars per month, indefinitely,” Almandoz said. “Not that we should not treat everybody. That’s not the message I’m saying. But if we’re looking at yield or value in terms of treating obesity in a setting with limited resources, it may be best to start with who is most likely to benefit.”
How They Created Four Obesity Types
Starting in 2015, Acosta and colleagues started comparing tests in people with normal weight vs. obesity. They used artificial intelligence and machine learning to classify obesity into 11 types at first. They realized this many obesity types were not practical for doctors and people with obesity, so they combined them into four phenotypes.
“The AI machine learning was followed by, as I like to call, H.I., or human intelligence,” he said.
The saliva test checks for about 6,000 relevant genetic SNPs. SNPs are “single nucleotide polymorphisms,” or changes in genes. Six thousand genetic changes may sound like a large number to check until you learn that people walk around with between 5 million and 6 million SNPs in their DNA.
The results are translated to a score that yields a low risk or high risk for Hungry Gut or other types of obesity. “You can have all six thousand genetic mutations, or you can have zero,” Acosta said.
Moving Forward
After the soft launch of Hungry Gut testing in April, Phenomix plans to continue studying their saliva test on other obesity types.
Acosta is not aware of any direct competitors to Phenomix, although that could change. “I think we’re the only diagnostic company in the space right now. But if it’s really a $14.8 billion market, we’re going to see a lot of diagnostic companies trying to do what we’re doing – if we’re successful,” he said.
An October 2022 report from Polaris Market Research estimates that the global market for obesity treatment – medications, surgery, and all others – was about $14 billion in 2021. The same report predicts the market will grow to $32 billion by 2030.
