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A New Genetic Test Could Determine Which Weight Loss Drug Will Actually Work For You

13 minute read

As popular as the latest drugs being touted for weight loss, including Ozempic, Mounjaro, and Wegovy, are on social media, like any medications, they don’t work in the same way for everyone. Not all are even approved to treat obesity, but are being used off label as a relatively easy way to shed pounds. While some users lose up to 20% or more of their body weight on these drugs, others struggle to shed single digit percentages.

That shouldn’t come as a surprise, since obesity isn’t a monolith and the factors that contribute to extra pounds are different for different people. In the same way that cancer doctors are now bringing more precision to which treatments they use by learning about the genes that drive people’s cancers, doctors who treat obesity are beginning to figure out the major contributors to an individual person’s obesity. That’s been catalyzed by the new class of more effective weight loss drugs that have been recently approved, with more on the way. Now that those medications are available, doctors are focusing on directing patients to the best treatments for them, whether it’s one of the newer drugs, some combination of older drugs, or a keener attention to diet and exercise.

While obesity and diabetes specialists have been applying this tailored approach to helping their patients lose weight for many years, it’s not as familiar for medical professionals who aren’t in these specialty fields, but are often people’s first medical contact when it comes to trying weight loss treatments. For them, having additional tools to differentiate between patients who are most likely to respond to the newest drugs, for example, and those who aren’t, could save people time, money, and frustration.

Dr. Andres Acosta, assistant professor of medicine at Mayo Clinic, has dedicated the past decade to developing such a tool. He and his team divide obesity into what he calls four phenotypes, or categories based on certain genetic factors that are primarily responsible for causing obesity:

  • Hungry Brain: people who never feel full
  • Hungry Gut: those who eat until they’re full but get hungry again within an hour or so
  • Emotional Hungry: those who eat to reward themselves or cope with emotional issues rather than based on physiological hunger
  • Slow Burn: those whose metabolism makes it difficult for them to burn calories properly.
  • What drives obesity, he says, should also drive which treatments people receive. Those who never feel full, for example, will struggle more with diet interventions, while those with metabolic imbalances might never lose enough weight even if they exercise to exhaustion.

    In 2021, Acosta co-founded a company, Phenomix, which took his years of research and developed a saliva test, called MyPhenome, that can distinguish the four types of obesity by analyzing a set of genes related to obesity that Acosta identified. In March, the company soft-launched its first test, for Hungry Gut, and this week launches Hungry Brain. Together, says Acosta, the two tests should identify the main contributor of obesity in about half or more of people with the condition. And the two tests will give doctors and patients clearer guidance about whether drugs like Wegovy and Rybelsus, and even the diabetes medications Ozempic and Mounjaro, will help them lose weight.

    How the test could change obesity care

    “When I see patients and talk about the options they have, and discuss how they are used, their cost, and the possible side effects, I always tell them that it doesn’t matter what they choose because at the end of the day, using the medications is like shooting in the dark,” says Dr. Daniela Hurtado, an endocrinologist at Mayo Clinic who worked with Acosta to develop and test the different obesity types. “We try something, and if it works, great. If it doesn’t, then we discontinue it and try another medication. It’s really trial and error.”

    The practice is pretty widespread in the obesity field, similar to the way doctors cycle through drug treatments for hypertension and depression, making educated guesses about which medication might work best for each patient based on their health history and symptoms. Even more entrenched is the idea that obesity isn’t a disease, but a characteristic for which patients can, and should, find their own solutions. “As a society, we haven’t been addressing obesity with appropriate medical care,” says Dr. Deborah Horn, medical director of the UTHealth Houston Center of Obesity Medicine and Metabolic Performance. “We’ve told people to eat less and move more, and left them to find solutions on their own, but now that we have beautiful, evidence-based treatments, we in the medical community have to make sure that this disease gets great medical care.”

    Part of that care involves matching patients to the right treatments as quickly and efficiently—and affordably—as possible. Horn has reached out to Phenomix to learn about offering MyPhenome to her patients, since having the test will go a long way toward accomplishing that.

    The newer weight loss drugs, which target the GLP-1 hormone that regulates appetite, can cost up to $1,400 a month, and many insurers don’t cover them, leaving patients to pay out of pocket or order them more cheaply from abroad, or find alternatives from compounding pharmacies that make copycat versions of the drugs. The test could weed out people who are currently on these expensive drugs but aren’t benefiting much from them. “It can help us figure out which patients to give this class of medications to, and do more targeted weight loss,” says Dr. Zaid Jabbar, president of the Illinois Obesity Society, and an obesity specialist in private practice, who is one of the hundreds of doctors waiting to offer MyPhenome for his patients. “It can also help us make sure we are using our resources effectively.”

    MyPhenome could also provide more solid justification for different combinations of drugs, beyond the GLP-1 medications, that doctors prescribe for weight loss using their experience and educated guesses about which are most likely to be effective. These include medications for conditions like migraine, depression, and addiction, which have also been linked to weight loss. “We look at comorbid conditions and use medications that match those conditions in combination,” says Jabbar.

    Read more: Teens Are Taking Wegovy for Weight Loss. But Doctors Have a Lot to Learn

    Not everyone who treats obesity and diabetes sees the necessity for such a test, however. Dr. Osama Hamdy, medical director of the obesity clinical program at Joslin Diabetes Center, who hasn’t requested the test and has only reviewed published data on the approach, says that most people with obesity will likely lose an appreciable amount of weight on a GLP-1-based drug, so testing them might not add that much more information to doctors’ decisions to prescribe them. For people with diabetes and obesity, the test might be slightly more helpful, since only about 22% of them are likely to respond to GLP-1 drugs. But even for those patients, Hamdy says he uses factors other than genetics to identify those patients, including age, their body mass index, the duration of their diabetes, and calculations of how well they respond to insulin. He’d like to see clinical studies that look at weight loss outcomes among people who were treated based on the test, and those who were not, to get a better sense of how much value phenotyping can add to optimizing weight loss therapies.

    How the test works

    Such data may come as more people use the test, and in the meantime, for doctors who don’t have the same level of expertise in managing obesity, MyPhenome could be a useful first step in narrowing down treatment options.

    Doctors need to prescribe the test first, and can do so by creating an account with Phenomix. The company provides doctors with a swab kit that patients use to collect saliva from both cheeks, which the doctor then sends to Phenomix. The company contracts with a genetic sequencing lab that analyzes the sample for 6,000 variants across nearly two dozen genes strongly related to obesity.

    Courtesy Phenomix

    Based on an algorithm that Acosta developed after studying the genetics of 1,000 people with obesity, the test then classifies people according to the most likely reason for their weight gain. The test focuses on genes related to things such as insulin resistance, energy intake, how quickly the stomach empties, as well as other factors such as how much people eat before feeling full and how often they feel hunger, which Acosta’s team documented when the participants consumed two meals a day in the research lab. “Once we had all the data, we put all that knowledge into a big gigantic pool and using machine learning, tried to find predictors and patterns of what predicts what type of eating,” says Acosta.

    Indeed, genetics are the primary driver of obesity in anywhere from 40% to 70% of people with the condition, and in trials, Acosta says, most participants fell into either the Hungry Gut or Hungry Brain categories.

    For $349, doctors and patients will, in 10 days or less after the lab gets the saliva samples, receive results that indicate whether the patient is positive or negative for both types. Based on the information he’s seen so far on the different obesity types, Jabbar, the Illinois obesity doctor, agrees that more than half of his patients will likely fit into either the Hungry Gut or Hungry Brain categories.

    He anticipates using the test not only for new patients to give him a “roadmap for how to navigate their weight management,” but also for those in the middle and even at the end of their weight loss journeys. For new patients, if they test positive for Hungry Gut, for example, that would give Jabbar more confidence prescribing a GLP-1 based weight loss drug like Wegovy or Rybelsus, which work by slowing the emptying of the stomach’s contents and absorption of food in the gut, in turn helping people feel full for longer. If they test positive for Hungry Brain, on the other hand, he would likely recommend other drugs like the combination of naltrexone and bupropion that work on the brain’s dopaminergic system to help the brain register satiety.

    Read more: Column: What We Get Wrong About Drugs Like Ozempic

    That could make managing patients more efficient. Currently Jabbar says it takes about six to nine monthly visits to settle on an effective weight loss program for his patients, but if the test can identify a productive treatment more quickly, people may only need three to four visits before they follow a schedule of less frequent maintenance visits.

    In addition, Jabbar says the test can even be useful for people who are in the process of reaching their weight loss goals, or even those who have already reached them. Identifying their obesity type can help doctors to wean them off of drugs they are taking that aren’t as effective in helping them lose weight.

    Weight loss drugs aren’t the only solution

    Insurance companies are not yet covering MyPhenome, since the test is so new. So patients will have to pay for it out of pocket—which Jabbar believes is still a good investment if it ends up saving people from spending money on medications that aren’t as effective for them. And for those whose test show they should take an expensive drug they can’t afford, the company provides a diet and exercise regimen tailored to specific obesity types designed to mimic the effects of the drug. “It’s important for people to understand that no matter what they do in terms of anti-obesity drug treatments, lifestyle—diet and exercise—are going to be the backbone,” says Hurtado, the Mayo Clinic endocrinologist who works with Phenomix. If they can’t take the drug, they can at least try to parallel the effects of the medications by changing their diet and exercise programs.

    For people with Hungry Gut, for example, a high protein diet that promotes the activation of hormones like GLP-1, just as the drug does, can help to suppress eating. Hurtado’s group at Mayo recommends such patients eat three to five smaller meals a day that are high in protein to keep the satiety signals in their gut active.

    For those with Hungry Brain, the Mayo group recommends a large volume diet, high in fiber, and low in calories. People with this type of obesity should try to eat one to two full meals a day in order to keep the stomach full so the distension signals the brain to stop eating.

    Read more: Column: What the Ozempic Obsession Misses About Food and Health

    Hurtado is now helming a study, sponsored by Phenomix, that will continue to gather data on test users and improve the algorithm’s ability to classify people into the different obesity types. “Any strategy to see obesity as a chronic condition, and not a patient characteristic, helps to individualize obesity treatment and allows me to tell patients that it’s not their fault,” says Hurtado. “So from a clinical perspective, it’s very, very relevant.”

    Where the test will be available

    About 315 doctors have contacted Phenomix about ordering the test, and 39 have already placed orders, according to Mark Bagnall, the company’s CEO. Phenomix has shipped about 200 test kits so far.

    The company is initially targeting obesity specialists, who will likely have the shallowest learning curve in applying the test. But ultimately, the test is meant to help non-specialists, including family doctors and internists, to manage obesity in their patients more efficiently.

    Horn, of UTHealth Houston, says there will never be enough specialists to treat patients with diabetes, not to mention the upwards of 70% of Americans who are overweight or obese. “We need to lean into primary care doctors, nurse practitioners, and physician assistants, who can do an excellent job of treating chronic disease,” she says. “This test can help them not only more quickly stratify patients, but also help them to continue learning more about the disease and educating themselves about obesity.” Arming more doctors and health professionals with the right tools for selecting the right anti-obesity therapies could finally turn the obesity curve around and bring more people to manageable, long-term weight control.

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