When stopped, new anti-obesity drugs appear to cause rapid weight regain

Ozempic, Wegovy, Zepbound or Mounjaro: this new generation of promising drugs against obesity has for months aroused the enthusiasm of millions of patients and the pharmaceutical sector, in a sector which is cruelly lacking in effective molecules. These medications mimic a hormone secreted by the intestines, GLP-1 (short for glugaco-like peptide 1), which stimulates insulin secretion and curbs the appetite by providing a feeling of fullness. But a question arises: what happens when you stop taking them?

According to a study published in the Journal of the American Medical Association on Monday, a significant part of the weight lost would be regained when treatment was stopped. Which raises fears of inducing a form of long-term dependence. The experiment was carried out with tirzepatide, a molecule present in the drug Zepbound from the American laboratory Eli Lilly. This treatment was approved in November in the United States as a treatment for obesity, a disease from which around 40% of adults suffer in the country. The Zepbound is not currently sold in France.

In the study published Monday, a cohort of 670 patients (48 years old and 107 kg on average, 70% women) first took a dose of Zepbound as a weekly injection, causing them to lose an average of 21% of their weight after 36 weeks. They were then separated into two groups: one continued to receive Zepbound, the other a placebo. After 88 weeks (more than a year and a half), those who had received the placebo had regained almost half of the weight lost, with a weight still 10% lower than at the very start of treatment. The group that continued Zepbound continued to lose weight, with a body mass 25% lower than at the start. Even though all patients received advice to eat less and exercise, these results “highlight “evidence the need to continue treatment to prevent weight regain and ensure continued weight reduction,” which provides significant cardiac benefits, write the authors.

This publication shows, as four other clinical trials had already done, that with this new generation of drugs, “weight is regained significantly” in the event of stopping treatment, they summarize. “Patients, caregivers and the public do not always understand that obesity is a chronic disease that requires ongoing treatment,” said Jeff Emmick, an Eli Lilly laboratory manager, in a statement responding to the study. Eli Lilly sells Zepbound for $1,060 per month in the United States - a high price, rarely reimbursed by the country's health insurance plans.

This new generation of medications increases the risk of gastrointestinal problems. And even if they are rarely serious, these side effects could perhaps, according to experts, ultimately outweigh the benefits of the treatment if it must be administered over the long term.