People who stop using the weight-loss jab Mounjaro not only tend to regain weight, but experience a reversal in other health improvements too, research suggests.
Mounjaro, which contains the active ingredient tirzepatide, has become a popular medication for weight loss, with studies suggesting that it can help people lose an average of 20% of their body weight after 72 weeks of treatment.
However, research has previously found that people who stop using tirzepatide tend to regain much of the weight they have lost.
Now experts studying results from a clinical trial known as Surmount-4 say other benefits seen with the medication, such as reduced blood pressure and lower levels of “bad” cholesterol, also go into reverse upon stopping the jabs.
Naveed Sattar, a professor of cardiometabolic medicine at the University of Glasgow who was not part of the team but was involved with previous work on the trial, said “the findings are not a surprise, as excess weight is a well-established driver of elevated blood pressure and impaired glucose control”.
He added: “Consequently, when weight lost through therapeutic interventions is regained, these cardiometabolic risk factors typically rise in proportion to the speed and extent of weight regain.
“Sustained weight management remains a critical challenge, but there is hope that newer, more affordable strategies to support long-term weight loss maintenance will emerge in the coming years.”
Studies have also suggested the use of tirzepatide and other weight-loss drugs in people with heart conditions reduces the risk of hospitalisation for heart failure or death from any cause. “So stopping them could remove a protective effect,” Sattar said.
Writing in the journal Jama Internal Medicine the researchers – which included experts from the pharmaceutical company that makes Mounjaro, Eli Lilly – report how they analysed data from the Surmount-4 trial, a study involving participants with obesity or who were overweight and had at least one weight-related health problem.
All participants received tirzepatide for 36 weeks, alongside diet and exercise support, before being randomly split into two equal-sized groups, one of which continued the medication for a further 52 weeks, while the other switched to a placebo for this period. Both participants and researchers were unaware at the time as to who was in which group.
The team focused on results from 308 participants who had lost at least 10% of their body weight by the end of the initial 36-week period before switching to the placebo, finding that one year after stopping tirzepatide, 82% of these participants had regained 25% or more of their initial weight reduction.
The team found that greater weight regain at the end of the study was associated with greater reversal of improvements not only in weight, but also in measures including waist circumference, levels of “bad” cholesterol, blood pressure, and blood glucose levels.
“Overall, at week 88, participants with 75% or more weight regain after tirzepatide withdrawal reversed cardiometabolic parameters to baseline (week 0) values,” the team write, although they note those with up to 50% weight regain still showed improvements in these areas compared with the start of the study.
The team say the findings “support the importance of long-term maintenance of weight reduction through lifestyle intervention and obesity management medications to sustain cardiometabolic benefits and improved health-related quality of life”.
Jane Ogden, the emeritus professor in the School of Health Sciences at the University of Surrey added that taking weight-loss jabs does not always create healthier eating and exercise habits, noting it can sometimes lead to poorer diets as people lose the motivation to eat well and prepare food.
“Once stopping taking the medication, people show weight regain as they return to their previous behaviours. With this can come a reversal in cardiac benefits as their diet and exercise behaviours return to how they were before,” she said.
Another piece of research suggests that women who stop using weight-loss medications such as tirzepatide or semaglutide before becoming pregnant or early in pregnancy tend to gain more weight while pregnant and have a higher risk of preterm delivery, gestational diabetes and hypertensive disorders of pregnancy than those who had not used such drugs.
However, Sattar cautioned that the latter study does not prove cause and effect, and said further trials are needed.
“Women receiving [weight-loss jabs] would likely have entered pregnancy at a lower weight than they otherwise would have, and this weight difference is extremely difficult to fully account for in observational analyses,” he said. “Therefore, the findings should be interpreted with caution.”
