A new analysis of the Surmount 4 clinical trial has confirmed what many clinicians suspected.
When people stop tirzepatide, the active ingredient in Mounjaro, most regain a significant amount of the weight they have lost and many of the improvements in blood pressure, cholesterol and blood sugar drift back towards where they started.
Mounjaro is a once weekly injection used for people living with obesity and for some people with type 2 diabetes. It acts on hormones in the gut and brain that influence appetite, fullness and how the body handles glucose.
Surmount 4 followed adults who were living with obesity or who were overweight with at least one weight related health problem.
Everyone in the study started tirzepatide alongside support with food choices and physical activity. Over the first 36 weeks they continued treatment and many people lost a substantial amount of weight.
People who tolerated the medicine and had lost at least 10 per cent of their starting weight were then randomised. Half carried on with tirzepatide for another year and half were switched, without knowing, to placebo injections.
The new analysis focused on the group who stopped active treatment and looked at what happened to their weight and their heart and metabolic health over the following 52 weeks.
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What happened when people stopped tirzepatide
One year after stopping tirzepatide, most people had regained a considerable share of the weight they had lost. Among those who had initially lost at least 10 per cent of their body weight, 82 per cent had put back on at least a quarter of that loss after a year on placebo.
The team also tracked changes in several important risk factors. People who regained more weight tended to lose more of the benefits seen during their time on tirzepatide. Larger weight regain was linked with:
- Increased waist size
- A rise in low density lipoprotein cholesterol, often called bad cholesterol
- Higher blood pressure
- Worsening blood glucose markers, including HbA1c
Those who regained three quarters or more of the weight they had lost returned, on average, to their starting levels for many of these measurements by the end of the study.
People who regained less than half of their weight loss still kept some improvements compared with where they had begun, which suggests that holding on to at least part of the weight loss continues to help the heart and circulation.
Why this happens
Excess body weight is closely linked with higher blood pressure, disturbed cholesterol patterns and poorer glucose control.
Professor Naveed Sattar, a cardiometabolic specialist who has worked on earlier stages of the Surmount programme, has pointed out that it is not surprising to see risk factors rise again when weight returns.
The faster and more completely weight is regained, the more those risks tend to climb.
In other words, tirzepatide does not permanently reset the system.
While the medicine is being taken and weight is reduced, risk factors improve. When treatment is stopped and weight returns, those gains fade.
What this means if you are using Mounjaro or a similar medicine
For many people, these findings reinforce the idea that obesity is a long term health condition rather than a short term project.
Treatments that act on appetite and hormones work while they are used.
Once they are withdrawn, the body often pushes back towards its old weight, especially if previous eating and activity patterns return.
If you are using tirzepatide or a similar medicine and are thinking about stopping, it is important to do this with support from your diabetes or weight management team.
Points to discuss include:
- How you will protect any weight loss you have already achieved
- A realistic plan for food, activity and sleep once injections stop
- Whether there is a need to adjust other medicines, such as blood pressure tablets or diabetes treatment
The new analysis also sits beside emerging research in women who stop these medicines around the time of pregnancy.
One observational study has reported that women who stopped drugs such as tirzepatide or semaglutide before or early in pregnancy gained more weight during pregnancy and had higher rates of complications than women who had not used these medicines.
That sort of study cannot prove cause and effect and needs more rigorous trials, but it underlines how important it is for anyone planning a pregnancy to talk to their specialist team well before they conceive.
