Weight rebounds after stopping GLP-1s

According to a new study published in The BMJ, people who stopped taking weight management drugs, including GLP-1s, typically regained the weight they lost and reversed their cardiometabolic improvements within two years.

Researchers analyzed data from 37 studies with 9,341 participants, which included randomized controlled trials, non-randomized trials, and observation analyses. The studies had an average treatment duration of 39 weeks and an average follow-up period of 32 weeks. The treatments included GLP-1s like semaglutide (Ozempic and Wegovy) and tirzepatide (Mounjaro and Zepbound), older weight-loss medications, and some drugs that were not available in the United States.

At the time of drug cessation, the average weight loss across all treatments was 18.3 pounds. Incretin mimetics, like GLP-1s, had higher weight losses on average: 22.3 pounds for all incretin mimetics and 32.4 pounds for newer incretin mimetics (semaglutide/tirzepatide). During the first year, estimated weight regain was 10.6 pounds (all treatments), 13.2 pounds (all incretin mimetics), and 21.8 pounds (semaglutide/tirzepatide).

Patients were projected to return to their baseline weight by 1.5 to 1.7 years, with those who previously took semaglutide and tirzepatide projected to gain back the weight fastest. This projected weight regain was roughly four times faster than someone who stopped behavioral programs, such as a diet.

All cardiometabolic measures, including HbA1C, fasting glucose cholesterol, triglycerides, and systolic/diastolic blood pressure, were also projected to return to baseline within 1.4 years of stopping weight management treatment.

"As obesity is a chronic and relapsing condition, prolonged treatment with WMM [weight management medication] may be required to sustain the health benefits," the researchers wrote. "This evidence cautions against short term use of WMMs, emphasizes the need for further research into cost effective strategies for long term weight control, and reinforces the importance of primary prevention."

In an accompanying editorial, Qi Sun, from Brigham and Women's Hospital and Harvard Medical School, noted that the study's findings challenge the idea that GLP-1 drugs "are a perfect cure for obesity."

"Issues such as high costs, side effects, and the inconvenience of injections are among some common reasons for discontinuing the medications," he added.

"This could involve a mixture of lowering the dose; decreasing the number of injections that are required; or oral versions of the drugs, which typically are going to be less effective but are probably going to be perfectly fine for weight maintenance," Yeo said.

Similarly, Evan Seigerman, a financial analyst at BMO Capital Markets, said he anticipates that doctors and patients will turn to GLP-1 pills for weight maintenance after they've reached a weight-loss plateau on injectable drugs.

Recently, Novo Nordisk launched the first-ever GLP-1 pill for weight loss in the United States; it's an oral version of its injectable GLP-1 treatment Wegovy. Eli Lilly is also working on its own GLP-1 pill for weight loss called orforglipron, with clinical trial data showing that it helped reduce people's weight regain after stopping injectable GLP-1 medications. 

Outside of medications, Sun suggested that healthy diet and lifestyle, bariatric surgeries, and public health measures like sugary beverage taxes could help some patients manage their weight after stopping weight-loss drugs.

Separately, Yeo said weight-loss drugs could be viewed as a tool to help people build healthier lifestyles, with a long-term goal of making it easier to stop taking the drugs and ultimately maintain their weight loss.

"I'm not saying this is easy, but you now have a set of tools, recipes, habits, a new bicycle route to work, that you can just call upon when the going gets tough," he said.

Advisory Board's weight-related resources

To help you address the growing use of weight management drugs, Advisory Board offers several resources.

This expert insight outlines the five biggest questions about weight management drugs and their answers. Similarly, this expert insight addresses what headlines get wrong about weight management drugs and what healthcare leaders should know instead.

Radio Advisory's Rachel Woods has also covered GLP-1 drugs on the podcast, discussing the potential future of these drugs and how they could help — or hurt — health systems' finances. Other useful resources include this expert insight on the five catalysts that will impact the future of obesity care and this research on four key elements of comprehensive obesity care.

Our weight management and obesity care resource library can also help leaders understand the current care landscape, manage innovations, and prepare for transformations in care.