Weight regain after Mounjaro means the loss of health gains, study finds
Regaining weight after stopping the weight-loss drug tirzepatide, sold as Mounjaro, is associated with a reversal of its cardiovascular health benefits, according to new research.
An analysis of participants in the Sumount-4 clinical trial found that more than eight in ten people regained at least twenty-five per cent of the weight they had lost within a year of ending treatment. Researchers reported that these individuals also saw previous improvements in cardiometabolic markers diminish.
A quarter of participants put back seventy-five per cent or more of the weight they had lost while taking tirzepatide. The study showed a clear trend: the more weight regained, the greater the reversal in markers such as blood pressure, lipid levels, HbA1c and waist circumference.
Publishing their findings in JAMA Internal Medicine, the research team, which included scientists from Eli Lilly, the manufacturer of Mounjaro, said those who kept their weight regain below twenty-five per cent by week eighty-eight largely maintained earlier gains in central adiposity, triglycerides, non-HDL cholesterol, fasting insulin and insulin resistance.
The authors noted that previous studies have suggested repeated cycles of weight loss and regain could harm health, partly because regained weight may consist disproportionately of fat mass.
Their analysis also showed that the rebound in triglycerides and non-HDL cholesterol after stopping tirzepatide was significantly greater among people who regained fifty per cent or more of the weight they had initially lost. Systolic blood pressure rose across all groups after treatment withdrawal, with the steepest increases in those who regained the most weight.
The researchers said further work is needed to understand mechanisms driving these changes that may be independent of weight gain. They added that the extent of HbA1c deterioration was also closely linked to the degree of weight regain.
“Although some improvement from baseline was still observed in all assessed cardiometabolic parameters despite partial weight regain of up to fifty per cent after one year of tirzepatide withdrawal, these findings support the importance of long-term maintenance of weight reduction through lifestyle intervention and obesity-management medications,” they concluded.
GPs have reported a surge in interest in tirzepatide since the NHS began offering it, initially to a small, high-need group earlier this year. NICE and NHS England agreed a phased rollout to avoid overwhelming primary care and to allow time for community weight-management services to expand.
Under NICE quality standards, GPs are advised to monitor patients for at least one year after completion of weight-loss drug treatment.
Professor Azeem Majeed, a GP and professor of primary care and public health at Imperial College London, said the findings underline that tirzepatide, like many anti-obesity treatments, should be regarded as a long-term therapy rather than a “quick fix”.
“Discontinuing treatment is likely to reverse much of the benefit unless ongoing behavioural, lifestyle or maintenance therapy is in place,” he said.
He added that the results pose important public-health questions. “If people are unable or unwilling to continue with drug treatment or maintain effective lifestyle changes, the initial health improvements will not be sustained, limiting long-term population-level benefit.”
He said clinicians must communicate clearly to patients that obesity is a chronic condition requiring long-term management.
“As these medications become more widely used, the NHS will need to consider how they can be provided as long-term therapies, and how to ensure that adequate support, including diet, physical activity and behavioural interventions, is consistently offered alongside pharmacotherapy.”