The appeal of weight-loss drugs is clear: For those who have struggled with the scale, the treatments can help achieve results and improve overall health (and do so quickly). But with any seemingly foolproof solution, there is always some catch, and the weight-loss drug market is no different. While they're often cited as "miracle drugs," a study published in JAMA Network Open in May found that 50 to 75 percent of people who start taking these medications end up discontinuing them within one year. There have been several theories presented as to why people may no longer need the miracle solution, but Sadiya Khan, MD, associate professor of medicine (cardiology) and preventive medicine (epidemiology) at Northwestern University Feinberg School of Medicine, wants to pinpoint exactly why.
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Khan, also a Northwestern Medicine physician, is the lead author of a JAMA Viewpoint opinion piece published earlier this week. In the viewpoint, the authors pointed out that these drugs, called glucagon-like peptide-1 receptor agonists (GLP-1 RAs), "are intended for long-term management" of both obesity and type 2 diabetes, but sustained use isn't always the case.
They specifically highlighted the SELECT trial, which looked at cardiovascular outcomes in patients with obesity and diabetes taking semaglutide. The treatment is better known by Novo Nordisk's brand names Wegovy and Ozempic, with the latter approved only for type 2 diabetes but often prescribed off-label for weight loss.
During the SELECT trial, almost 30 percent of individuals stopped using semaglutide, but "real-world estimates" of GLP-1 RA discontinuation are much higher—between 50 and 75 percent after 12 months. According to Khan, different factors are likely at play, including cost and the idea that they can be a quick fix for weight loss.
"While research is needed to quantify and identify the drivers, we hypothesize that there are likely many issues," Khan said in a press release. "First and foremost, the high cost of these therapies is likely a large barrier. Also, unlike therapies that are used to treat blood pressure or cholesterol, the perception that these are not chronic disease therapies may also be contributing. For instance, some individuals think they will stop taking them once they've lost weight while others are only using them cosmetically and not for management of a chronic disease."
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In the press release, the authors referenced a 2023 survey that may give more weight to the idea that people are only taking the medications to lose weight and stopping once they do so. When KFF Health Tracking Polls asked adults if they'd "be generally interested in taking a safe and effective prescription weight loss drug," 45 percent of surveyed adults said they would. However, after they learned that they would regain weight after discontinuation, only 14 percent said they'd still be interested.
In the viewpoint, Khan and her fellow authors pointed to data illustrating this, as well as the resultant negative effects on heart health.
"Trials of discontinuation demonstrated rapid regain of weight and worsening of cardiometabolic parameters after stopping semaglutide or tirzepatide," the authors wrote, referencing another GLP-1 RA marketed under Eli Lilly's brand names Mounjaro and Zepbound.
But while many people aren't staying on the medications, Khan said the theorized reasons why are not definitive. In addition, experts are not sure how to keep patients on the medications to continue reaping the benefits, specifically the reduction in cardiovascular disease events. According to the authors, this is a pressing concern.
"The staggeringly high discontinuation rates of GLP-1 RA should raise alarms for clinicians, policy makers, and public health experts," Khan said in the press release.
