Weight Loss Drugs May Be Working Too Well — and That’s Becoming a Problem
For years, the race in pharmaceutical labs was simple: make weight loss drugs more powerful. Now, scientists are beginning to ask a harder question — how much weight loss is actually too much?
New trial results for retatrutide, an experimental drug being developed by Eli Lilly, have put that question front and center. Participants with obesity and knee osteoarthritis lost an average of 28.7 percent of their body weight after 68 weeks on the highest dose — significantly more than the roughly 20 percent seen with currently available drugs like Wegovy. But the trial also saw a higher-than-usual dropout rate, with between 12 and 18 percent of participants leaving the study due to side effects. Eli Lilly confirmed that at least some of those patients quit because they felt they were losing too much weight — a development that has alarmed researchers outside the company. The trial involved 445 participants and was sponsored by Eli Lilly; full data has not yet been published.
“We’re not trying to force a specific magnitude of weight loss in every patient,” said Dr. David Hyman, Eli Lilly’s chief medical officer, adding that retatrutide is intended for patients who need to lose more weight than existing medications can achieve. “We’re not of the belief that the most potent weight loss medicine is required for everybody, or that that’s even the goal.”
A Question Without a Clear Answer
What constitutes “too much” weight loss remains medically murky. Some patients on GLP-1 drugs report they simply don’t look or feel right. Others and their doctors worry that drastically reduced appetite means they’re not eating enough to stay healthy. Experts have also raised concerns that these medications could trigger or worsen disordered eating in vulnerable patients.
Maureen Chomko, a diabetes care and education specialist in Seattle, says she sees the consequences firsthand. Patients can become so nauseated on these drugs that when they do manage to eat, they reach for crackers rather than nutritious meals. “We’re having a good hard look at what this person is eating, why they aren’t eating,” she said, noting concerns about patients becoming malnourished and dehydrated.
Industry Responds With Flexible Dosing
Novo Nordisk, maker of Ozempic and Wegovy, says it has already adjusted its approach. In a late-stage trial of a new drug called CagriSema, the company used a flexible dosing schedule — allowing patients to stay at a lower dose if the drug was working well or if side effects became difficult to manage. Novo Nordisk submitted CagriSema to the US Food and Drug Administration for approval in December and expects a decision later this year.
Dr. Ania Jastreboff, director of the Yale Obesity Research Center and a researcher who has studied retatrutide, says the guiding principle must shift. “We have to use the dose that the patient needs,” she said. “The underlying question is needing to approach and treat obesity as we would any other chronic disease” — calibrating treatment individually, rather than chasing the highest possible number on the scale.
