Despite data suggesting that more than half of the patients (53.6%) discontinued GLP-1 drugs within a year, and 72.2% within 2 years, guidance on how to appropriately wean patients off the drugs, or perhaps convince them to continue taking them, is lacking.

Faced with sparse evidence, clinicians find themselves relying on their best judgment. Some patients are being forced to “exit” the drug regimens, while others say they don’t want to continue. Regardless of the reason, clinicians need to take the next steps.

“There’s a lot of controversy about what to do because there are no randomized clinical trials,” Diana Thiara, MD, medical director of the Weight Management Program at University of California San Francisco, told Medscape Medical News. “Right now, it feels a bit like the wild, wild west, where a provider’s opinion plays a really big role in what they decide to do. I don’t know any other parts of medicine like that, where your own lived experience dictates what you think your patient should do. It’s bizarre.” 

When implementing a strategy, she added, “our colleagues ask, ‘where’s the proof that what you’re doing will work?’ For me, the proof is in the patients who do it right and benefit.”

Five Reasons Patients Want to Discontinue

There are several key reasons that patients want to stop taking a weight-loss drug or are forced to do so. Either way, clinicians need to be ready to take action.

Insurance. Our experts agreed that lack or loss of insurance coverage — the latter, usually due to either changing formularies or changes in employer-based coverage — is a major reason for discontinuation. A recent study published in JAMA Network Open affirmed that “higher prescription rates among privately insured individuals indicate that socioeconomic factors influence access.”

Changes due to loss of insurance coverage usually are “abrupt” and “unfair,” Thiara said. “We have to come up with some evidence we can use to help these patients who may not want to stop taking the drug but don’t have a choice.”

Rekha Kumar, MD, associate professor at the Weill Cornell Medical College in New York City told Medscape Medical News she has many patients who switched to direct-to-consumer cash pay options, or to manufacturer-based programs such as Novo Care or Lilly Direct. “But obviously, those are expensive, too,” she said — though some relief may be available in coming months.

Gastrointestinal side effects. Another big reason for stopping or pausing is gastrointestinal-related side effects — most commonly, nausea, vomiting, diarrhea, and constipation. Meghana Anugu, MD, an internist and obesity medicine specialist at Emory Healthcare in Atlanta, told Medscape Medical News she had an extreme case of a patient who developed a hernia from straining so much from constipation. The team wasn’t managing that side effect because the patient hadn’t revealed it.

“We also see patients who have horrible nausea and vomiting, especially on Ozempic,” she said. “So anecdotally, in my practice, patients seem to be tolerating Zepbound or Mounjaro better than Ozempic of Wegovy.”

Pregnancy. Notably, the new weight-loss drugs have not been studied in pregnancy, nursing, or breastfeeding. In its first guideline on GLP-1s, the World Health Organization excluded pregnant women from its recommendation that the drugs could be used long term for treating obesity. Yet “trying to conceive” is one of the most common reasons Kumar’s younger patients give for wanting to stop, and she has some strategies for dealing with it (see the next section).

New medical condition. A new and serious medical condition, such as cancer requiring chemotherapy, is another reason to stop, Kumar said. “Although there’s not a contraindication, these meds are still new and they’re impacting so many body systems that for my patients initiating cancer treatment, we do stop or pause.”

“I just don’t want to do it anymore.” Thiara has a number of patients — mostly those paying out-of-pocket — who say they simply don’t want to continue. And Kumar has patients who insist they’ve achieved their health and weight goals and want to try going without the drug. Others may want to stop to reduce the number of medications they’re taking.

Five Strategies to Help Patients Discontinue or Stay

Have a conversation. Although it’s admittedly a “time consuming and personalized process,” having a conversation with the patient is important initially, to understand their biology and psychology but also when decisions need to be made about discontinuing treatment or staying with it and perhaps accepting changes, Kumar said. “Traditionalists want evidence for practice decisions, but it’s hard to have evidence when it’s so nuanced, and every case is different.”

Anugu’s conversations regarding discontinuing treatment depend on whether or not the patient has “time, energy, money, and insurance coverage,” she said. If they do, she asks whether the patient is interested in slowly bringing the dose down over time and checking in to see how they’re doing or adding another oral medication that works in a different pathway. That conversation will help point to next steps.

Switch drugs. If her patient doesn’t have time, energy, and resources, and perhaps was forced to stop because of loss of insurance or intolerable side effects, then Anugu is more likely to prescribe an oral anti-obesity medication that might be more affordable or better target their underlying pathophysiology.

Thiara noted, “The ‘by-the-book’ answer for patients who were forced to stop would be to switch to a different FDA-approved oral medication such as phentermine, phentermine/topiramate or naltrexone/ bupropion.”

But Thiara ends up doing “a lot of off-label use of metformin.” For individuals with obesity also dealing with insulin resistance or polycystic ovary syndrome, “metformin can be extremely helpful,” she said. In addition, metformin could be appropriate for women who want to attempt pregnancy because it’s “a lot safer” for that population.

Kumar has a “very strict plan to bring patients off the meds 2 months before trying to conceive and maintain them on meds that are safe such as metformin if they do get pregnant,” she said. “If someone wants to get pregnant and is at extremely high risk for weight gain and gestational diabetes, I might switch them to liraglutide, although that still needs to be stopped before pregnancy.”

Taper the drug dose. If a patient wants to stop because of personal preference, “we go down the way we went up,” Thiara said. “But before we go down, I usually say ‘let’s think about depression or other diseases where we come off meds. Let’s see if you can be stable for 6 months on your treatment before making changes.”

Some patients are willing to go that route while others continue to say no. “That means we do a slow-down titration, each month going down a dose and checking in and seeing what happened. Are they more hungry? Eating less nutritiously? Drinking more alcohol? Gaining weight? If the answers are yes, that’s a very obvious signal that this strategy isn’t going to work,” she said.

“But if a patient is fine with each down titration, they can try to come off,” she said. “The key is for them to continue following the principles of mindfulness around eating, monitoring nutrition, staying active, and focusing on sleep and stress reduction. But at the first sign of change, they need to check back in.”

Extend the interval between doses. For patients who simply want to take fewer medications, “we can try to reduce exposure,” said Kumar. “That could mean spacing it out. Instead of dosing weekly, dosing every other week, and reducing the dose to a maintenance dose.”

“None of this is evidence-based,” she emphasized. “There are no randomized controlled trials. But I’m a huge proponent of this strategy.”

Kumar sees about 2400 patients yearly, and she has patients who take less and less of the drug and maintain their weight loss.

“I have some patients on the lowest dose once a month. That’s proof in the real world that somebody can do this,” she said. “Even if a patient gains back 5 or 10 Ib, that’s still better than gaining back all the weight. And cycling off for a period of time until they feel like their appetite and hunger signals are overwhelming them averages out to about $200 a month.”

Use as needed. “I don’t recommend this, but I do see patients who are doing it, especially when they’re purchasing from compounding pharmacies,” Anugu said. “Once they’ve come off the drugs, they take them ‘as needed’ — meaning prior to going on a cruise or events they think will be high-stress, or where they’re likely to have dietary indiscretion. I’ve also heard about people who stop the drug but buy a supply and take it if they see they’re weight is going up. These are not recommended strategies, but they’re what some people are doing in the real world right now.”

Anugu noted that regardless of drug use, pause or exit plan, affordable, accessible lifestyle programs should be available and continued. “Ideally, I would have all my patients — with or without extra weight — enrolled in lifestyle programs where they’re optimizing their sleep, stress, physical activity, and nutrition and avoiding risky substances. These are the pillars of a healthy lifestyle. But the fact is, the American healthcare system pays for acute services and procedures. We’re not investing enough in prevention.”

Thiara reported being a member of scientific advisory boards for Novo Nordisk, Eli Lilly, and Boehringer Ingelheim. Kumar reported being the senior medical advisor to Found Health. Anugu had no disclosures. 

Marilynn Larkin, MA, is an award-winning medical writer and editor whose work has appeared in numerous publications, including Medscape Medical News and its sister publication MDedge, The Lancet (where she was a contributing editor), and Reuters Health.