Help Patients Prevent Weight Gain After Stopping GLP-1s

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Weight loss drugs have surged in popularity — in part because they work. Patients on glucagon-like peptide 1 (GLP-1) agonists like liraglutide, semaglutide, and tirzepatide (which is technically also a glucose-dependent insulinotropic polypeptide agonist) can lose 10%, 20%, or even 25% of their body weight.

But if those patients stop taking GLP-1s, they tend to regain most of that weight within a year, studies showed.

“These drugs work inside the person from a biologic point of view to alter appetite,” said Robert Kushner, MD, an endocrinologist and professor at Northwestern University Feinberg School of Medicine, Chicago, Illinois, who specializes in obesity medicine. “And when the drug is gone, that disease comes back.” 

Ongoing treatment may seem like the obvious solution, but reality can complicate that. High costs, supply shortages, and faltering insurance coverage can render the drugs inaccessible.

Often, “patients are told by their insurers that they are no longer going to cover a GLP-1 for obesity,” said Carolyn Bramante, MD, MPH, an assistant professor at the University of Minnesota Medical School, Minneapolis, Minnesota, who sees patients at the M Health Fairview weight management clinic.

Other barriers include side effects like nausea, diarrhea, stomach pain, and vomiting. Some patients simply don’t want to take a medication forever, instead choosing to take their chances keeping the weight off sans drug.

If your patient must stop GLP-1s, or really wants to, here’s how to help.

  • Find out why the patient wants to go off the GLP-1. Ask them to help you understand, suggested Jaime Almandoz, MD, associate professor of internal medicine and medical director of the University of Texas Southwestern Medical Center’s Weight Wellness Program. Sometimes, the patient or family members worry about safety, Almandoz said. “They may be concerned about the risks and may not have had an opportunity to ask questions.” Almandoz reviews the drug safety data and tells patients that studies show, on average, people gain back two thirds of the weight they’ve lost within a year. You’re not trying to persuade them, only to equip them to make a well-informed choice.
  • Don’t let bias affect treatment decisions. Patients on GLP-1s often ask: How long will I have to take this? The reason: “We’re biased to believe that this is not a disease state, that this is a character flaw,” said Sean Wharton, MD, PharmD, medical director of the Wharton Medical Clinic for weight management in Burlington, Ontario, Canada. Remind your patient that obesity is not a personal failure but rather a complex mix of genetic and biological factors.
  • Give patients a primer on the biology of obesity. Science shows that when we lose weight, our bodies fight back, trying to return to our highest-ever fat mass. Changes in neurohormones, gut hormones, satiety mechanisms, metabolism, and muscle function all converge to promote weight recurrence, Almandoz said. To explain this to patients, Almandoz compares gaining fat to depositing money in a savings account. “When we try to lose weight, it isn’t as simple as withdrawing this money,” he’ll tell them. “It is almost like the money that we put into the savings account is now tied up in investments that we can’t liquidate easily.”
  • Prepare patients for an uptick in appetite. When patients stop GLP-1s, their hunger and food cravings tend to increase. “I explain that GLP-1 medications mimic a hormone that is released from our intestines when they sense we have eaten,” said Almandoz. This signals the brain and body that food is on board, decreasing appetite and cravings. Ask patients what hungry and full feel like on the medication, Almandoz suggested. “Many will report that their hunger and cravings are low, that they now have an indifference to foods,” said Almandoz. Such probing questions can help patients be more aware of the medication’s effects. “This positions a more informed conversation if medications are to be discontinued,” Almandoz said.
  • Help their body adjust. “Slowly wean down on the dose, if possible, to avoid a big rebound in hunger,” said Bramante. If your patient has the time — say, they received a letter from their insurance that coverage will end in 3 months — use it to taper the dose as low as possible before stopping. The slower and more gradual, the better. Almandoz checks in with patients every 4-8 weeks. If they’re maintaining weight well, he considers decreasing the dose again and repeating with follow-up visits.
  • Substitute one intervention for another. In general, maintaining weight loss requires some intervention, Wharton said. “But that intervention does not need to be the same as the intervention that got the weight down.” If the patient can’t continue a GLP-1, consider an alternate medication, cognitive behavioral therapy, or a combination of the two. When patients lose coverage for GLP-1s, Bramante sometimes prescribes an older, less-expensive weight loss drug, such as phentermine, topiramate, or metformin. And sometimes, insurers that don’t cover GLP-1s (like Medicare), do cover bariatric surgery, a potential option depending on the patient’s body mass index, overall health, and comorbidities, said Almandoz.
  • Create a habit template. Kushner asks patients who have successfully lost weight to take an inventory of everything they’re doing to support their efforts. He’ll have them describe how they plan their diet, what types of food they’re eating, how much they eat, and when they eat it. He’ll also ask about physical activity, exercise patterns, and sleep. He logs all the habits into a bulleted list in the patient’s after-visit summary and hands them a printout before they leave. “That’s your template,” he’ll tell them. “That’s what you’re going to try to maintain to the best of your ability because it’s working for you.”
  • Prescribe exercise. “Increasing exercise is not usually effective for initial weight loss, but it is important for maintaining weight loss,” said Bramante. Tell patients to start right away, ideally while they’re still on the drug. In a study published last month, patients on liraglutide (Saxenda) who exercised 4 days a week were much more likely to keep weight off after stopping the drug than those who didn’t work out. (The study was partially funded by Novo Nordisk Foundation, the charitable arm of Saxenda’s maker, also the maker of semaglutide meds Ozempic and Wegovy.) By establishing strong exercise habits while on the medication, they were able to sustain higher physical activity levels after they stopped. Ask your patient to identify someone or something to help them stick to their plan, “whether it’s seeing a personal trainer or being accountable to a friend or family member or to themself through record keeping,” said Kushner. Learn more about how to prescribe exercise to patients here.
  • Help them create a “microenvironment” for success. Kushner asks patients which of the recommended dietary habits for weight loss are hardest to follow: Eating more plant-based foods? Cutting back on ultra-processed foods, fatty foods, fast foods, and/or sugary beverages? Depending on the patient’s answers, he tries to recommend strategies — maybe going meatless a few days a week or keeping tempting foods out of the house. “If you go off medication, food may become more enticing, and you may not feel as content eating less,” Kushner said. “Make sure your own what we call microenvironment, your home environment, is filled with healthy foods.”
  • Rely on multidisciplinary expertise. Obesity is a complex, multifactorial disease, so call in reinforcements. “When I see someone, I’m always evaluating what other team members they would benefit from,” said Kushner. If the patient lacks nutrition knowledge, he refers them to a registered dietician. If they struggle with self-blame, low self-esteem, and emotional eating, he’ll refer them to a psychologist. It can make a difference: A 2023 study showed that people who lost weight and received support from professionals like trainers, dietitians, and mental health therapists regained less weight over 2 years than those who did not receive the same help.
  • Reassure patients you will help them no matter what. Ask patients to follow-up within the first month of quitting medication or to call back sooner if they gain 5 pounds. People who stop taking GLP-1s often report less satisfaction with eating, or that they think about food more. That’s when Kushner asks whether they want to go back on the medication or focus on other strategies. Sometimes, patients who gain weight feel embarrassed and delay their follow-up visits. If that happens, welcome them back and let them know that all chronic conditions ebb and flow. “I constantly remind them that I am here to help you, and there are many tools or resources that will help you,” Kushner said. “And dispel the notion that it’s somehow your fault.”

Kushner reported participation on the medical advisory board or consultancy with Novo Nordisk, WeightWatchers, Eli Lilly and Company, Boehringer Ingelheim, Structure Therapeutics, and Altimmune. He added he does not own stock or participate in any speaker’s bureau. Almandoz reported participation on advisory boards with Novo Nordisk, Boehringer Ingelheim, and Eli Lilly and Company. Wharton reported participation on advisory boards and honoraria for academic talks and clinical research with Novo Nordisk, Eli Lilly and Company, Boehringer Ingelheim, Amgen, Regeneron, and BioHaven.

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