A recent study published in The BMJ has found that stopping weight loss medications leads to rapid weight regain and a reversal of improvements in heart and metabolic health markers, such as high cholesterol and high blood pressure. According to the research, individuals who discontinue these drugs regain weight at an average rate of 0.4 kg per month, with both weight and risk markers for diabetes and heart disease expected to return to pre-treatment levels within less than two years.
The study also reports that the rate of weight regain after stopping medication is nearly four times faster compared to those who had lost weight through diet and physical activity changes, regardless of how much weight was initially lost during treatment.
"This evidence suggests that despite their success in achieving initial weight loss, these drugs alone may not be sufficient for long term weight control," the researchers stated.
The development of effective medications for obesity management, including glucagon-like peptide-1 (GLP-1) receptor agonists like semaglutide and tirzepatide, has changed the approach to treating obesity. However, about half of people prescribed GLP-1 drugs stop taking them within a year. Understanding what happens after discontinuation is therefore important.
Researchers from the University of Oxford reviewed data from registries and databases, analyzing trials and observational studies comparing licensed weight loss medications in adults with non-drug interventions or placebo. In total, 37 studies involving 9,341 participants were included. The average duration of treatment was 39 weeks with a follow-up period averaging 32 weeks.
After stopping medication, participants regained an average of 0.4 kg per month and were projected to return to their original weight within 1.7 years. Cardiometabolic risk markers were predicted to revert to baseline within 1.4 years after discontinuing the drugs. The monthly rate of weight regain was also higher following drug cessation than after behavioral programs by 0.3 kg per month.
The authors noted limitations such as only eight studies evaluating newer GLP-1 drugs and limited follow-up periods after stopping medication. Additionally, few studies had a low risk of bias.
Despite these limitations, the researchers used three different analytical methods that yielded similar results, which they say strengthens their conclusions.
They concluded: "This evidence cautions against short term use of weight management medications, emphasises the need for further research into cost effective strategies for long term weight control, and reinforces the importance of primary prevention."
A US researcher commented in an editorial linked to the study: "The study findings casted doubt on the notion that GLP-1 receptor agonists are a perfect cure for obesity." He added: "People taking GLP-1 receptor agonists should be aware of the high discontinuation rate and the consequences of cessation of medications." He emphasized: "Healthy dietary and lifestyle practises should remain the foundation for obesity treatment and management, with medications such as GLP-1 receptor agonists used as adjuncts." He concluded: "Such practises not only help prevent excess weight gain but can also lead to numerous health benefits that go beyond weight control."
