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A New Concern About Weight Loss Drugs: What if They Work Too Well?
Some patients in a clinical trial of one new drug lost so much weight that they became concerned and dropped out.
www.nytimes.com
A New Concern About Weight Loss Drugs: What if They Work Too Well?#-a-new-concern-about-weight-loss-drugs-what-if-they-work-too-wellSome patients in a clinical trial of one new drug lost so much weight that they became concerned and dropped out.
By Dani Blum
Feb. 18, 2026
Leer en español
For years, scientists pushed to create medications capable of shedding as many pounds as possible. These days, the industry is easing off the gas.
According to recent top-line results from a trial of retatrutide — a compound under development at Eli Lilly — patients who had obesity along with knee osteoarthritis shed 28.7 percent of their body weight on average, measured after 68 weeks at the highest dose. By comparison, weight-loss drugs presently on the market have produced roughly 20 percent body weight reduction across that same span.
Side effects drove somewhere between 12 and 18 percent of trial participants to quit — a share larger than what is usually seen in studies of existing weight-loss drugs. At least a portion of those people left the trial believing they were losing too much weight, according to the company, which unsettled some researchers outside the study. Eli Lilly funded the trial, which enrolled 445 participants. Definitive conclusions about why patients dropped out remain difficult, since the full data set has yet to be published.
Dr. David Hyman, chief medical officer at Eli Lilly, said, “We’re not trying to force a specific magnitude of weight loss in every patient.” Retatrutide, he added, will target patients who need to shed more pounds than other medications could help them lose. He also said, “We’re not of the belief that the most potent weight loss medicine is required for everybody, or that that’s even the goal.”
Pinpointing exactly what qualifies as excessive weight loss is tricky. Some people taking GLP-1s fret that their appearance simply seems off. Others — patients and doctors alike — worry that consuming so little food is harmful to health. Experts said that in still other cases, these medications might encourage disordered eating.
Concerns like these are being watched closely by researchers employed by the companies developing the drugs.
Dr. Ania Jastreboff, who directs the Yale Obesity Research Center and is a leading investigator who has studied retatrutide for Eli Lilly, said, “We have to use the dose that the patient needs.” She explained that the aim is to keep patients on the smallest effective dose. “The underlying question is needing to approach and treat obesity as we would any other chronic disease,” Dr. Jastreboff said.
Novo Nordisk — maker of Ozempic and Wegovy — says its strategy has shifted. For a late-stage trial of a new compound called CagriSema, which seems roughly as effective as other injectable obesity drugs now on the market, the company adopted a flexible dosing schedule. Under that approach, participants who couldn’t handle the side effects, or for whom a lower dose was already working, were allowed to remain at the smaller dose. Novo Nordisk filed for Food and Drug Administration approval of CagriSema in December and anticipates a greenlight later this year.
Maureen Chomko, a diabetes care and education specialist based in Seattle, treats patients with diabetes who take drugs such as Ozempic. When someone is shedding too many pounds, she said, “we’re having a good hard look at what this person is eating, why they aren’t eating.” Nausea from the drugs can be so severe, she said, that when patients finally manage to eat, a kale salad with salmon is not what they reach for — instead they’re trying to keep down a handful of crackers. She said she worries about people becoming malnourished and dehydrated on these medicines and urges patients to set alarms to remind themselves to eat
Ms. Chomko is working with the biopharmaceutical company Amgen on clinical trials for MariTide, a new monthly weight loss compound that is in development. She is helping train the dietitians who are involved with the studies, working to ensure participants get enough vitamin D, calcium, fiber and protein, nutrients that she frequently sees people on these medications failing to get in sufficient amounts.
Ms. Chomko said excess weight loss was “a visible sign that these meds have pushed someone too far.”
“But I think what I’m more concerned about is the invisible,” she added.
Doctors are trying to figure out how to advise patients who seem to be losing too much weight. Dr. Janice Jin Hwang, the division chief of endocrinology and metabolism at the University of North Carolina School of Medicine, frequently sees patients who have hit what she called their “metabolic targets” on these medicines: Their blood sugar has fallen, their cardiovascular metrics have stabilized and they have reached their target weight. But then they want to lose even more.
“There are more nuanced discussions now about, how much weight does a person need to lose?” she said. And there is no clear pathway for doctors to ensure patients lose a Goldilocks amount of weight: not too much, not too little. She often ends up embarking on a kind of trial and error, seeing if patients can maintain their progress on a lower maintenance dose, with the understanding that they will almost certainly need to stay on the drugs for the rest of their lives to do so.
Dr. Sahib S. Khalsa, a psychiatrist at the University of California at Los Angeles Health, coauthored a paper in 2024 about these medications titled: “Highway to the Danger Zone?” In it, the authors warn that people who take these drugs need to be strictly monitored to ensure that they eat and hydrate sufficiently and do not lose too much weight. The paper also notes that the medications are particularly risky for people with histories of disordered eating.
Since that paper was published, Dr. Khalsa said he has only grown more concerned.
Dr. Andrew Kraftson, a clinical associate professor at the University of Michigan Medical School, said that he had to stop a patient from continuing on the medications, because the person wanted to keep losing weight, even when there was no clear medical benefit to doing so.
“We have to recognize that society has brainwashed us all to certain beauty standards that are not always in alignment with health standards,” Dr. Kraftson said. “And so just because someone can starve themselves to get down to a lower weight doesn’t mean that we should make that easier by giving them an injection to promote anorexia.”
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