A study published in the Journal of the American Medical Association this week shows that when people lost weight on Eli Lilly’s Zepbound and then switched to a placebo after eight months of treatment, they gradually regained about half of the weight.
By comparison, people who stayed on the drug were an average of 25% lighter at the end of the 88-week study. Even patients who switched to a placebo still weighed about 10% less at the end of the study, and their waist size shrank — indicating that some benefits from the therapy were retained.
While intriguing, the result wasn’t a surprise: Novo Nordisk showed similar results in a trial of its drug Wegovy that was that was published in 2021 in the same journal.
Obesity researchers are only beginning to explore what happens after people lose weight with GLP-1 drugs such as Wegovy or Zepbound. Most trials of the drugs have only lasted a year or so. While some type of long-term drug therapy is likely to be needed — just as it is with other diseases like high blood pressure — exactly what form it will take is a big unknown, says Robert Kushner, an obesity doctor at Northwestern University Feinberg School of Medicine.
“This whole idea of maintenance is a huge black hole,” Kushner told my colleague Madison Muller in a recent interview. “We're going into this area but we don't have the long-term game figured out.”
This is certain to be a big topic of conversation among obesity experts over the next few years. “We just figured out weight loss and now we need to focus more on maintenance,” Angela Fitch, an obesity doctor and president of the Obesity Medicine Association tells me via email.
When Kushner gives presentations explaining that obesity will require lifelong treatment, “everyone then asks, ‘What does that mean?’” Doctors don’t have answers to that question yet, he admits.
While some patients may be able to take breaks from GLP-1 therapy, insurance rules make this difficult, Fitch writes. That’s because once someone stops taking an obesity drug, insurers often won’t cover treatment again until a person has regained enough weight to go back above the body mass index threshold that defines obesity.
“The current rules keep patients on meds because when they need to go back on — because it is a chronic disease — they cannot, so they stay on,” Fitch says.
Lilly is conducting an ongoing study on whether patients can switch to a lower dose of Zepbound after their weight loss plateaus. Given the huge number of people suffering from obesity — and the high price of these drugs — staying on medicines like Zepbound and Wegovy indefinitely will be an astronomically expensive option. Zepbound currently lists for $1,060 a month and Wegovy lists for $1,349 a month.
If older obesity pills, such as phentermine, can help people keep the weight off, that would be a more affordable option, Kushner says. — Robert Langreth