A study warns of the 'rebound effect' of Ozempic and other weight-loss drugs.

One of the biggest fears of those who managed to lose weight through dieting was the so-called "rebound effect" : regaining the lost weight, or even more, after stopping the diet. Now, in the era of weight-loss drugs , a meta-analysis published in BMC Medicine warns that patients prescribed weight-loss medications may regain their weight after discontinuing the prescription.

The study, which analyzed data from people receiving weight-loss drugs in 11 randomized trials, suggests that while the magnitude of weight gain varies depending on the specific drug, there is a general tendency for weight regain after treatment ends.

The U.S. Food and Drug Administration (FDA) has approved six anti-obesity drugs to aid in weight loss, including orlistat (which works by preventing some of the fat in food from being absorbed in the intestines), phentermine-topiramate (which decreases appetite and increases feelings of fullness), and semaglutide (which helps regulate blood sugar and appetite. Ozempic, Rybelsus, and Wegovy belong to this family).

Xiaoling Cai, Linong Ji, and colleagues conducted a meta-analysis of 11 studies from around the world that investigated weight change in patients after discontinuing the drug. In total, the authors analyzed data from 1,574 participants in treatment groups and 893 in control groups. Of the 11 studies included in the meta-analysis, six focused on GLP-1 receptor agonists (those in the Ozempic family); one on the dual GLP-1 and GLP receptor; one study focused on orlistat; two studies on phentermine-topiramate; and one study on naltexone-bupriopion.

The authors controlled for various contributing factors, including medication type, the presence of diabetes, and the presence or absence of lifestyle changes such as diet or exercise. Their analysis found that the drugs were associated with significant weight loss during use, followed by weight regain starting eight weeks after discontinuation, which continued for an average of 20 weeks before stabilizing.

Study participants experienced significant periods of weight regain at eight, 12, and 20 weeks after stopping treatment. The amount of weight regained depended on several factors, including the type of medication participants were taking and the consistency of their lifestyle changes. For example, participants who completed a 36-week course of tirzepatide , a GLP-1 RA commercially available as Mounjaro , regained nearly half of their previously lost weight after switching to a placebo.

The authors note that the meta-analysis did not include studies on lifestyle interventions or bariatric surgery, which limits the ability to compare different weight loss approaches within the context of the study. They also point out that weight regain has also been reported with other weight loss methods, such as gastric bypass and vertical banded gastroplasty.