Whether pharmacologic treatment of obesity with GLP-1 receptor agonists (RAs) should continue indefinitely once initiated was debated at the 37th Brazilian Congress of Endocrinology and Metabolism (CBEM 2026) held in Rio de Janeiro, Brazil, from August 26 to 29, 2026.

Bruno Halpern, MD, PhD, Brazilian endocrinologist, president of the World Obesity Federation, and vice president of the Brazilian Association for the Study of Obesity and Metabolic Syndrome, argued in favor of long-term treatment, citing consistent weight regain and loss of cardiometabolic benefits after treatment discontinuation.

Maria Teresa Zanella, MD, PhD, professor at the Federal University of São Paulo in São Paulo, Brazil, expressed reservations about routine indefinite treatment for all patients. She advocated an individualized approach, with dose reduction or discontinuation considered in selected patients who could maintain their weight through lifestyle measures and other interventions.

The differing views highlighted an ongoing clinical question in obesity management: whether GLP-1 RAs should generally be considered long-term therapy or whether treatment can be reduced or discontinued in selected patients who maintain weight loss without medication.

“The more effective the treatment, the less effective the absence of treatment,” said Halpern. To support his position, he cited the expanded STEP 1 study, funded by Novo Nordisk and published in 2022 in Diabetes, Obesity, and Metabolism. One year after discontinuing 2.4 mg semaglutide, the 327 participants had regained, on average, two thirds of the weight they had lost, while cardiometabolic measures, including blood pressure and lipid levels, had returned to their previous values. “If we treat obesity properly, diabetes will be a rare disease in the future,” he said.

Halpern also cited the study by Sumithran and colleagues published in 2011 in The New England Journal of Medicine. The study found that 14% weight loss produced persistent changes in the nine appetite-regulating hormones studied, including ghrelin, which increased significantly and remained elevated 1 year after the initial weight loss, promoting weight regain.

Regarding the cardiovascular (CV) safety of GLP-1 RAs, Halpern cited the SELECT study funded by Novo Nordisk. The study included patients aged 45 years or older with preexisting CV disease and a BMI ≥ 27 who did not have diabetes. Semaglutide (2.4 mg) reduced the risk for major CV events by 20%.

Halpern emphasized that some benefits of these medications are unrelated to weight loss or glycemic control and that access to treatment remains limited, in part because of cost and stigma. “These barriers have not yet been overcome. We must demand greater access to antiobesity treatment and a reduction in the stigma associated with it,” he concluded.

When to Stop Treatment

Zanella agreed that obesity requires ongoing treatment but disagreed with the idea that this necessarily means continuing the same class of medication indefinitely. “If lifestyle changes and other adjustments are implemented during weight loss, the patient may be able to maintain their weight afterward [after discontinuing treatment],” she said.

According to Zanella, decisions to continue or discontinue GLP-1 RAs should be made on a case-by-case basis. “When a patient has very severe obesity, I recommend not discontinuing the medication if they can continue taking it. But in younger patients and those with less severe cases, we may be able to maintain [their weight] through lifestyle changes,” she emphasized.

There is no established protocol for gradual tapering; however, Zanella believes that lower doses may be sufficient in some cases. She cited the SURMOUNT-MAINTAIN study, funded by Eli Lilly, and published in May 2026 in The Lancet. The study found that reducing the dose of tirzepatide helped maintain weight loss in adults with obesity, whereas discontinuation led to significant weight regain.

“In clinical practice, many individuals do this even though it’s not indicated in the package insert or even the patient does it on their own to save money. They reduce the dose or the number of clicks slightly or space them out a bit, but when they realize they’re wanting to eat more again, because their appetite is increasing, they increase the dose again,” Zanella said. “But each strategy needs to be tested in each patient to determine the lowest exposure necessary to maintain weight.”

Zanella identified three main situations that may require treatment discontinuation: unaffordable cost, lack of response, and complications during use. “The prices are exorbitant, and many individuals end up abandoning treatment. What good is a medication if only a minority will be able to use it?” she asked. “There are too many side effects for too little benefit,” she added.

Among the complications that may warrant a change in treatment, pancreatitis, severe reflux esophagitis, severe constipation, and colitis have been cited. To illustrate the risks of continuing treatment despite adverse reactions, Zanella presented the case of an 18-year-old woman who had been overweight since childhood (71.1 kg; BMI, 27). She could not tolerate semaglutide and experienced adverse reactions to tirzepatide but continued treatment and experienced rapid weight loss. “This caused a significant reduction in lean body mass, and the patient ended up with a worse body composition than she had before treatment,” said Zanella.

In these cases, alternatives include the combination of naltrexone and bupropion (Contrave), sibutramine if there are no contraindications, and the combination of sibutramine and topiramate.

Speaking with Medscape’s Portuguese edition, Zanella, said, “These medications are not as potent as GLP-1 RAs, and there is also no evidence that they reduce, for example, the [risk for] CV events, but they are alternatives. What you shouldn’t do is take medication and neglect lifestyle changes. For it to work, everything has to be combined.”

Alexander Koglin Benchimol, MD, a physician and researcher from the Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione in Rio de Janeiro, who moderated the debate, emphasized that the two positions are complementary rather than opposing.

“We all agree that the use of incretin-based medications can improve individual’s self-esteem, appearance, and quality of life. The important thing is to discuss with the patient what makes the most sense for them, and whether it’s possible to reduce the doses at some point,” he noted. “And also, to assess for which patient profiles oral medications would be more accessible, in order to maintain treatment consistency.”

Regarding dose spacing, the consensus was unanimous; because of a lack of robust evidence, this strategy is not recommended. “From a pharmacokinetic standpoint, it’s not a good idea. I don’t recommend it for the vast majority of patients, even when it works for one or two of them,” concluded Halpern.

Washington Castilhos has been a science and Brazilian health journalist for more than 20 years. He holds a master’s degree in science, health, and technology communication from the Oswaldo Cruz Foundation in Rio de Janeiro and a doctorate in education and biosciences communication from the Federal University of Rio de Janeiro, which includes a doctoral internship at Paris 8 University in Saint-Denis, France.

This story was translated from Medscape’s Portuguese edition.