Weight regain after Mounjaro means reversal of health benefits, finds study

Regaining weight after stopping taking weight loss jab tirzepatide (Mounjaro) is also associated with a reversal in the cardiovascular health benefits, researchers have reported.

An analysis of people taking part in the Sumount-4 clinical trial showed that not only did more than eight in ten participants regain 25% or more of their weight loss a year after stopping, they also lost the cardiometabolic improvements they had previously seen.

One in four participants put back 75% or more of the pounds they had lost while taking tirzepatide and the analysis showed the greater the weight gain, the greater reversal in markers of blood pressure, lipids, HbA1c and waist circumference.

Reporting the findings in JAMA Internal Medicine, the researchers including experts from Eli Lilly, the makers of Mounjaro, said participants who maintained the weight reduction to less than 25% regain at week 88 also maintained the benefits seen in central adiposity, triglycerides, non-HDL cholesterol, fasting insulin, and insulin resistance.

They noted that other studies had found repeated cycles of weight reduction and weight regain may be detrimental to health because regained weight may be proportionally higher in fat mass.

Their analysis showed that the reversal of improvement in triglycerides and non-HDL cholesterol on stopping tirzepatide was significantly greater in participants who regained 50% or more of their initial weight reduction.

But systolic blood pressure significantly increased after stopping tirzepatide across all categories of weight regain, with a higher rise observed with greater magnitudes of weight regain, they added.

More work is needed to understand what mechanisms might be involved that are independent of weight gain, the researchers said.

Reversal in improvements to HbA1c was also linked to extent of weight gain, they added.

‘Although some improvement from baseline was still observed in all assessed cardiometabolic parameters despite partial weight regain of up to 50% 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 people asking for tirzepatide after the NHS began offering the drug – initially to a very small group of those with greatest need – this summer.

NICE and NHS England had agreed a phased roll out of the drug to buy time for community weight loss services to be put in place and to avoid overwhelming GPs.

GPs have also been advised under NICE quality standards to monitor patients who have taken weight-loss medication ‘for a minimum of one year’ after treatment is completed.

Professor Azeem Majeed, a GP and professor of primary care and public health at Imperial College London said: ‘The findings reinforce that tirzepatide – like many anti-obesity treatments – needs to be viewed as a long-term intervention rather than a short-term “quick fix.”

‘Discontinuing treatment is likely to reverse much of the benefit unless ongoing behavioural, lifestyle, or maintenance therapy is in place.’

He added that from a public-health perspective, it raises important concerns.

‘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.’

Clinicians also need to be clear in communicating 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 – diet, physical activity and behavioural interventions – is consistently offered alongside pharmacotherapy.’