Ozempic-like medications may preserve 25 percent of lost weight after stopping

A fresh analysis indicates that people who discontinue Ozempic-like medicines retain roughly 25 percent of the weight they lost for as long as a year afterwards. However, there is an important unknown: researchers do not know how much of that loss comes from muscle rather than fat.

This unresolved medical question draws attention to a little-studied effect of semaglutide, tirzepatide and other medicines used for type 2 diabetes or weight management. Early research suggests that lean muscle mass could account for 40 to 60 percent of the weight lost while taking these treatments.

Although weight regain after stopping these medicines is well established, the composition of the returning weight remains uncertain.

"If the regained weight is disproportionately fat, individuals may ultimately be worse off than before in their fat-to-lean mass ratio, which may have adverse consequences for their health," explains medical researcher Brajan Budini, co-first author of the study by a team at the University of Cambridge in the UK.

Ozempic-like medicines and weight regain

The team's published paper offers a wide-ranging assessment of evidence on weight gain after treatment ends. It is also the first to model the pattern of weight regain for up to 52 weeks following treatment cessation.

Managing weight after treatment is stopped matters because more than a billion people worldwide live with obesity. GLP-1 medicines have shown considerable effectiveness, in some cases enabling people to reduce their body weight by 20 percent or more.

These drugs imitate glucagon-like peptide-1 (GLP-1), a naturally occurring hormone that helps regulate blood sugar and suppress appetite. But gastrointestinal and other side effects, high costs, and prescription-related difficulties mean that around half of patients stop taking GLP-1 medicines in their first year.

"Drugs such as Ozempic and Wegovy act like brakes on our appetite, making us feel full sooner, which means we eat less and therefore lose weight," says Budini.

"When people stop taking them, they are essentially taking their foot off the brake, and this can lead to rapid weight regain."

Evidence from GLP-1 treatment studies

To estimate how much weight patients put back on after ending treatment, the researchers reviewed 48 relevant studies. They quickly identified major inconsistencies and limitations across the evidence.

Some research monitored patients' weight for only a few weeks, while the timing of follow-up appointments after medication was stopped varied substantially. Taken together, the authors say post-GLP-1 weight gain "has been largely underexplored in the literature."

The team therefore selected only a small number of high-quality papers that fulfilled specific requirements. Studies needed to be randomised, involve more than 100 participants, report weight loss of at least 3 kilograms (6.6 pounds), and include at least one assessment 12 weeks after the medicine had been discontinued.

Their systematic review was consequently narrowed to six randomised controlled trials (RCTs), involving more than 3,200 people. These particularly robust trials tracked participants for as long as 52 weeks after they stopped using weight-loss medicines.

This relatively small meta-analysis found that patients who had taken GLP-1 medicines regained weight rapidly at first, before the rate gradually eased. By one year after stopping treatment, they had regained 60 percent of the weight lost during treatment.

Muscle mass, fat mass and treatment cessation

Using these findings, the researchers modelled what could happen beyond 52 weeks. Their projections suggest that weight regain starts to level off at 60 weeks and slows after patients have regained 75 percent of the weight they lost during treatment. The reason is unclear.

One possibility is that the medicines enable patients to establish healthier dietary habits or produce physiological changes, including altered hormone levels or hypothalamic function.

Yet a substantial share of lost weight is muscle, and it is unknown whether lean mass returns as quickly as fat mass once treatment ends. In addition, newer and more potent drugs, including semaglutide and tirzepatide, are less effective at protecting lean mass - meaning they drive greater weight loss regardless of where that weight comes from.

Prescription approaches involving gradual dose reductions could therefore help patients maintain at least their fat loss. It is also useful for clinicians to support healthy eating and exercise, both of which are essential to long-term wellbeing.

"It's important that people are given advice on improving their diet and exercise, rather than relying solely on the drugs, as this may help them maintain good habits when they stop taking them," concludes medical researcher and co-first author Steven Luo.

The research was published in eClinicalMedicine.