Researchers are delving into the complexities of obesity, revealing why injectable GLP-1 drugs, while effective for many, fail for others. The article explores the diverse factors contributing to obesity, emphasizing the need for personalized treatment approaches based on individual genetic, hormonal, and behavioral profiles. It highlights the importance of identifying root causes and tailoring interventions, including medication combinations and lifestyle changes, to achieve successful and sustainable weight loss.
Injectable GLP-1 drugs have been a game-changer for many people with obesity. But as researchers discover why the medicines fail for others, they are gaining insights about the complexity of the condition.
Obesity shaped Anna Olson's earliest notions of herself, when she saw a photo and thought,"Oh, I look different than the other kids." Olson's obesity began in toddlerhood, ran in her family, and left her with a chronic hunger hard to satiate. Dozens of diet, drug and exercise regimens didn't work, and advice from doctors was always the same: Eat less."And I'm kind of like, 'Well, it's what I'm doing now. What else can I do?'" she says, and the response, again, was:"Well, you just got to eat less." In fact, science now shows obesity is far more complex — with numerous genetic, biological, neurological, lifestyle, metabolic and behavioral factors contributing to it. Doctors, patients and drug companies have learned a lot more in recent years about obesity and what works — or doesn't — since the new class of obesity treatments known as GLP-1 drugs have come to market. Although obesity manifests one way — excess weight — doctors say there are perhaps dozens of different forms of it. For treatment to work, therefore, root causes must be identified, then addressed, for each person. Obesity doctors and researchers say within several years, they expect treatment will be more customized to meet the needs of each patient. For Olson, genetic testing indicated she likely has several genetic and hormonal factors setting her hunger and satiety sensors out of whack. One of the GLP-1 drugs — Ozempic — worked briefly, but it turned out another, Zepbound, better recalibrated Olson's hormone imbalance. It was only when she started tackling her specific obesity drivers that Olson began losing lots of weight — 65 pounds to date, as she remains on the medicine."I've been able to keep it off," she says.Use of GLP-1 drugs is already huge and is set to become even more common, as the medicines become cheaper, with more variations, including the recently launchedOzempic and Wegovy are the brand names for a drug called semaglutide. Zepbound and Mounjaro are the brands of a drug called tirzepatide. Both are Within a few years, doctors say, there also will be more ways to determine an individual's specific obesity factors, which will enable a more precise targeting of the root causes of their obesity, similar to how chemotherapies can target specific cancer subtypes.have shown a significant portion of patients lose less than 5% of their body weight on the drug, though they may experience other metabolic improvements., a gastroenterologist and hepatologist at the Mayo Clinic. Acosta says early research indicates genetic markers might be measured to predict, for example, whether a person might not respond well to GLP-1 medicines.: Hungry Gut, Hungry Brain, Emotional Hunger, and Slow Burn. Each category has different hormonal or lifestyle factors that drive obesity. For example, someone with emotionally driven eating habits might not benefit as much from GLP-1 drugs.Acosta says also, those with abnormalities in their gut hormones tend to lose more weight on GLP-1 medicines, while some people with"Hungry Brain" genetic markers may have a broken neural pathway that prevents the drug from being as effective for that group. For those people, Acosta says, often earlier generations of weight-loss medicines — or a combination of new and old drugs — work best.Anna Olson says this kind of personalization was key. Through genetic testing, she found out her phenotype is"Hungry Brain." She also found out she has, a genetic disorder that predisposes her to eat too much. Knowing that, she says, reduced her sense of stigma and helped her find the most fitting combination of medications for her. Now 36, she says her cholesterol and blood sugar levels have improved, and she's closer to her dream of traveling further afield from her native Minneapolis."When I was more overweight than now, there was absolutely no way that I could do that."The chemistry of a person's gut microbiome, their proclivity toward addiction, or the molecular shape of their hormone receptors can all affect the drug's efficacy, she says."The medication might be degraded faster in one individual than in another," she says, which might also explain the different responses to GLP-1s.showed that those who rely on GLP-1 drugs tend to gain back the weight at a faster rate when they stop treatment, as compared to those who rely on behavioral change.roughly half of those who take GLP-1 drugs lose 15% or more of their weight, and"because the potential of those drugs is so incredible for that half, everyone who takes them thinks they're going to be in the half that have that experience." Manne-Goehler says what's often forgotten is that obesity is a chronic, lifelong condition."One tool does not work for each person, and one tool often is not enough over the lifetime of a person to control or to mitigate the health impact of that condition," she says. But over the next few years, she says, at least there will be more tools to better target treatment.Yuki Noguchi is a correspondent on the Science Desk based out of NPR's headquarters in Washington, D.C. She started covering consumer health in the midst of the pandemic, reporting on everything from vaccination and racial inequities in access to health, to cancer care, obesity and mental health.After second Minneapolis killing, San Diego elected officials say ‘Rubicon crossed’ and ICE is ‘executing American citizens’KPBS keeps you informed with local stories you need to know about — with no paywall. Our news is free for everyone because people like you help fund it.
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