The big question about obesity drugs: Can people ever stop taking them?

The big picture: The class of injectable drugs known as GLP-1 agonists has been used for years for treating Type 2 diabetes, and those patients typically receive the treatment indefinitely.

• But in the last few years, they've been increasingly recognized for their ability to increase insulin sensitivity and curb hunger. Two of the drugs have been approved for weight loss.
• There are still questions about how the drugs work, including how long patients should stay on them.
• Patient advocates argue this very debate shows how obesity has been viewed differently from other chronic diseases — as a matter of poor willpower, rather than one driven by biology.
• But even among providers, whether weight-loss patients should expect to sign up for a lifetime of treatments is not a settled question, particularly as an increasing amount of real-world data shows many patients stop taking the drugs within a year, and a majority stop taking the drugs within 24 months. That's partly due to challenging side effects as well as coverage limits.

State of play: On one side, the argument for treating obesity like any other chronic disease means it makes no sense to wean patients off the drugs.

• "We wouldn't say, 'Well, great, your blood pressure is now down to normal, so stop the medication and we expect your blood pressure to stay down,'" Susan Yanovski, co-director of the National Institutes of Health's Office of Obesity Research, told Axios.
• She pointed to studies that have found patients taking semaglutide — the active ingredient in Novo Nordisk's Wegovy and Ozempic — regained two-thirds of their lost weight within a year of getting off the drugs.
• Anecdotally, clinicians told Axios they've seen patients quickly gain the weight back, and sometimes more.
• "These medications work while you're taking them. If for some reason you stop the medication, then you will regain the weight," said Enrique Elli, a bariatric surgeon at the Mayo Clinic who said he often sees patients seeking a more permanent solution.

The other side: Some experts say we are just beginning to understand how the drugs rewire the brain, suggesting more data is needed to show if they might instead serve as a bridge to less intense therapies and lifestyle changes that can help patients keep off weight.

• Companies like Lark Health, which helps health plans manage the GLP-1s, and Calibrate, which provides GLP-1s and support directly to consumers, are developing clinical studies to demonstrate how to graduate patients of the drugs.
• Among the questions they're examining: whether it's possible to shift patients to much lower doses, switch to a less expensive medication, or use the drugs intermittently to maintain weight loss, Lark's chief medical officer, Peter Antall, told Axios.

• Antall said it's not surprising that many participants in previous GLP-1 trials gained the weight back afterward. "They stopped the medication at the highest dose, cold turkey," Antall said.
• Clinicians generally slowly increase the dosage for new GLP-1 patients to minimize the discomfort of side effects. There should be a similar tapering process for patients alongside support, Antall said.
• "Let's help them slowly learn to keep those eating habits that they've developed while on GLP-1s, even if they don't feel as full after a normal-sized meal," Antall said.
• Weaning may be plausible for some patients, but there isn't yet enough clinical data to support taking patients off the drugs, said Yanovski of the NIH obesity office.
• "Right now, what I tell patients is that, if the medications work, they'll need to be on medication indefinitely," she said.

Yes, but: Clinicians didn't entirely dismiss arguments for weaning.

• Many insurers are refusing to cover these drugs for obesity, and finding a way to use the drugs in a more cost-effective manner could help improve access to coverage.
• Patients who could benefit greatly from these drugs, including kids, may find the idea of taking the drugs in a limited way more palatable.
• No matter which side of the argument, there's seemingly broad agreement that a strong patient support service component is needed to improve the success of the drugs.