Rising prices for new-generation weight-loss drugs and concerns about long-term use have some users rethinking their approach.
“The weeks after I stopped Mounjaro were crazy. The hunger was uncontrollable. I went to bed thinking about food and woke up thinking about food. If I’d been at an all-you-can-eat buffet, I would have eaten it all. It was the worst three weeks of my life,” recalls Karen Lay, 56, who works in financial services.
Like many of the approximately 1.5 million people in the UK taking GLP-1 weight-loss drugs (named after the hormone they mimic in the brain), Lay found that when she wanted to stop, support from her prescriber was minimal. She gained 5kg in just four weeks, and her experience is reflected by research showing most people who take weight-loss drugs regain all of the lost weight within 10-20 months of stopping.
This led Britain’s National Institute for Health and Care Excellence (Nice) to update its guidelines last month to recommend a year of structured support for people transitioning off obesity medication.
With the majority of people accessing the drugs privately, and hefty recent price rises for one of the most popular, Mounjaro, many may be questioning their approach to weight-loss drugs in the first place.
“These drugs mimic the hormone that makes you feel full, so when you stop taking them, appetite bounces back to its natural level,” says Susan Jebb, professor of diet and population health at the University of Oxford. “The trials are clear – people need good dietary advice and behavioural support alongside these drugs and structured support when treatment ends.”
So what is actually happening in your body when you stop taking GLP-1 medications, why does the weight come back so rapidly, and is it possible to prevent the return of unwelcome pounds?
What happens when you stop Mounjaro or Wegovy
Week 1
Weight-loss drugs are injected weekly, so they don’t vanish from your system overnight. Wegovy/Ozempic (semaglutide) has a half-life of about a week, while Mounjaro (tirzepatide) is around five days. That means that after the final jab, the levels in the body drop by roughly half every five to seven days.
After a week, there will be about 50% of the drug left in your system, so hunger levels and feelings of fullness will start to flicker back, but some appetite suppression should remain.
Weeks 2-8
By day 10, there will be roughly 25% of Mounjaro left in your system, so this is when many report that hunger pains and “food noise” (persistent, repetitive thoughts about food when you aren’t even hungry) start to return in earnest.
Lay’s appetite roared back just two weeks after stopping Mounjaro.
“I’ve always had food noise and struggled with my weight most of my life, but this was uncontrollable; I just couldn’t stop eating,” she recalls. “My daughter had to stage an intervention; she threw crisps away and decluttered the house of unhealthy food because my cravings were so bad.”
By weeks four to eight, the drugs will have cleared from most people’s systems. On the plus side, any side effects should also have gone.
Professor Tricia Tan is a consultant in diabetes, endocrinology and metabolic medicine at Imperial College London. She explains: “The effect of Mounjaro or Wegovy is to stimulate your GLP-1 (and also GIP in the case of Mounjaro) receptors in your pancreas, your blood vessels, your stomach and your brain. This stimulates insulin release from the pancreas; reduction of appetite and interest in food via the brain; and a slowdown of stomach emptying, so you get fuller faster when you eat.
“When someone stops these medications, they stick around in the body for about one to two months after the last dose. During this time, the effects noted above will slowly dissipate, and we would expect a patient to start eating more.”
If the person had diabetes before taking the medications, they would also expect their blood sugar to rise.
Eight weeks and beyond
A recent meta-analysis of 11 randomised trials by BMC Medicine found that people started to put weight back on as early as eight weeks after stopping, with significant regain by 12 weeks, and then steady increases until 20 weeks (five months), before weight gain began to plateau. The amount of weight regained depended on the type of medication and whether that individual also made lifestyle changes.
Over time, many people can also experience a return to their previous blood pressure and cholesterol levels. There is also a risk of ending up lighter on muscle and heavier on fat than when you started.
Rachael Joy is a nurse and chief clinical officer for private prescriber SheMed.
She explains: “If people aren’t eating the right diet and doing some body weight or strength training exercises, there is a risk of losing muscle when on the weight loss medications. Then, when they stop and regain the weight, studies show that, unfortunately, they can replace that muscle with fat.”
According to Jebb, research also shows that the quicker you lose weight, the faster you put it on: “We don’t completely understand why that is, but if you combine biological susceptibility to weight gain, together with a world where food is everywhere and cheap, then weight loss maintenance is hard however you lose it,” she says.
How to come off weight loss drugs effectively
Experts agree that gradually reducing the dose in consultation with your doctor is the best way to stop taking weight-loss medications, and slowly get used to the return of “food noise”.
“We slowly reduce the dose so that cravings don’t come back too aggressively. Sometimes, if someone has another condition, say an underlying fatty liver, and their blood tests are showing that it’s coming back, we might actually keep them on a very low dose – not to lose more but to stabilise health and weight,” says Joy. “There are lots of studies being done on microdosing, but we need more research in this area.”
Although Wegovy is currently only approved by Nice for two years in the UK, and Mounjaro has no current time limit, many experts believe that given the complexity of obesity as a condition, some may need to stay on weight-loss drugs for much longer or even for life.
“It’s important to realise that we don’t use these medications only for weight loss,” says Tan.
“These drugs are known to reduce risks of strokes and heart attacks, improve blood pressure, reduce cholesterol, improve liver health, improve sleep apnoea, reduce risks of diabetes and its complications, improve osteoarthritis and reduce risks of kidney disease. These benefits come from long-term treatment.”
The problem with long-term use is the fact that most people don’t want to be on medication for life, particularly if they experience side effects. The eye-watering cost and recent price hikes (thank you, President Trump) will put many people off too.
Lay decided to stop Mounjaro because even though it took away her appetite, she only lost 5kg in total, and she wanted to be able to enjoy going out for dinner with friends again. Before taking weight-loss drugs, she was 15st 9lb (99kg) and a size 18.
“Yes, I wanted to lose weight, but I also wanted to be normal. I like food. I enjoy going out to eat with my girlfriends. On Mounjaro, all I wanted was a glass of water. I didn’t want to be like that for the rest of my life,” she says.
How not to regain weight after weight-loss drugs
Weight-loss drugs are not meant to be taken in isolation, but combined with changes to diet, exercise and people’s relationship to food, and these changes need to start while people are still taking the medication.
“Medication alone is not a silver bullet. Yes, you will lose weight, but if you don’t make other lifestyle changes, when you stop the weight tends to pile back on, and you can feel out of control,” says Dr Luke Pratsides, a GP for the private provider Numan, which has a large community of patients taking weight-loss drugs.
Exercising is important. “Strength training to avoid muscle loss while losing weight is important,” says Joy. “We find that a lot of our members when they first join aren’t exercising at all. We’re not saying you have to immediately start lifting weights – start slowly with body weight exercises like squats and lunges.”
A protein-rich diet also helps people maintain muscle and feel full for longer.
Pratsides emphasises developing healthy habits and preparing strategies for coming off the medication in advance. “For example, somebody might have had a snacking habit at three o’clock in the office because they felt a bit of a dip, and as soon as you take away the drug, that desire is going to come back,” he says. “So what strategy will you use to help with that?”
Research shows that weighing yourself regularly is also important. “The moment you’ve gained a couple of kilos, you need to take action as it becomes increasingly hard to get back on track,” says Jebb.
Learning mindfulness and really understanding when and why you eat is also vital. If you eat when you’re stressed, for example, what will you do instead to manage that emotion?
After stopping Mounjaro, Lay went on the 1:1 Diet by Cambridge Weight Plan. Now, she is 2st lighter, has gone from a size 18 to a size 12, has lost 15% of body fat and 5 inches from her waist. She credits much of this to working with her 1:1 diet coach, Loren, demonstrating how important support is for sustained weight loss.
“Loren helped me a with a lot of coping mechanisms. I travel a lot for work, so I have to plan in advance for what I am going to eat. At a restaurant with clients, I would take a glass of wine, but not actually drink it, so I didn’t have to explain why,” Lay says.
“I kept a journal and realised I ate a lot out of boredom or for something to do with my hands when watching TV. If I’m hungry, I now just sip water. I do three strength-training sessions a week, and also fit in a long walk. I’ve started to see definition in my arms for the first time, I’m full of energy and enjoy shopping again with my daughter.”
Lay has also halved her blood-pressure medication and no longer needs asthma inhalers.
Weight-loss drugs may not have been the answer for Lay, but her story underlines the reality that the jabs are only the beginning – what happens next depends on the support, habits and health strategies you put in place.