What happens when you stop taking one?

Transcript

Welcome to the sofidex Health Drive podcast series. Today we are talking about stopping, and about what happens to your weight when the injections that helped take it off come to an end. Perhaps a clinic letter has given you a date, or the price has gone up, or the side effects have simply worn you down. And somewhere at the back of your mind is a sentence you have read more than once, which is that everybody puts it all back on.

And the answers on offer tend to arrive in two unhelpful shapes. Either the drug fixed something for good and you will be fine, or it was a shortcut all along and the weight was never really yours to keep. So we want to ask a more useful question. Not whether some of the weight comes back, because for most people some of it does, but how much, how fast, and whether anything you do changes it.

We will go through the trials that stopped these drugs on purpose and watched what happened next, including the one designed to take willpower out of the picture. We will look at what a large review found about how quickly weight returns, and why your blood pressure matters more than your scales. And we will finish with the things that seemed to hold after treatment ended, most of which you can start well before your last dose.

None of this is a reason to stop a medication early, or to stay on one you cannot afford. And if some of the weight does come back, none of what follows is a verdict on you. One thing before we start. This is health information, not medical advice, and nothing in it is a substitute for talking to your own doctor about your own treatment. What we can tell you is where all of it came from — 7 published sources, all listed with the episode. I'd like to do this one through a single person again. Not a real patient. Someone we're making up, so we can follow him all the way. Call him Mark. He's fifty-three, he drives a bus, and for nearly two years he's been on semaglutide through an NHS weight clinic. He's lost a bit over three stone. His blood pressure tablet got halved last summer. And last week a letter arrived saying his two years finish in March. So he did what everybody does. He looked it up. And the first thing he found was a sentence saying everybody puts it all back on.

And that's the sentence this episode is about. Because it's half right, and the half that's wrong is the half that's frightening him. Some weight usually comes back after stopping. That much is solid. But "all of it", and "everybody", and "nothing you can do" — those are three separate claims. And they don't all hold. So I want to go slowly. What actually happens when the drug stops. What the trials actually tested. Why it isn't his fault. And what Mark can do between now and March, which is more than he thinks.

Start with the bit he's most scared of, then, because I think it's the bit most people are scared of. Is it true that it all comes back? Every pound of it?

Not all, no. But most, for most people, over about a year. And I'd rather he heard that plainly now than found it out in April. The clearest picture comes from a trial called STEP 1. People took semaglutide for well over a year — sixteen months or so — and then stopped. Drug stopped, lifestyle programme stopped, all of it. And a group of them were followed for another year. That follow-up found that a year after stopping, people had regained two-thirds of the weight they'd lost. So not all. Two-thirds. Which is a lot. But it isn't the sentence Mark read.

Two-thirds still sounds like a technicality to me, though. If you've lost three stone and two of them come back, that's going to feel like failing, whatever the paper calls it.

It does feel like that. But look at where those people ended up, because that's the number nobody quotes. At the end of the extension they were still five point six per cent lighter than when they started, on average. And almost half of them still had at least five per cent off at the end. Five per cent sounds small. It isn't nothing. The trial itself calls five per cent or more clinically meaningful. So the summary cuts both ways. Most of it came back. And a real chunk of people kept a meaningful amount.

Is there any way of telling which group Mark's going to be in? The ones who keep some, or the ones who lose the lot?

Not in advance, no. Nobody can look at Mark and tell him. But there's one pattern in that trial worth knowing, because it's a bit counter-intuitive. In the STEP 1 extension, the people who lost the most tended to regain the most, but still ended up keeping more than the people who'd lost less. So big losers bounce back harder. And they still finish further ahead. Mark's lost a good amount. So the regain may feel fast. But he's starting the race from further down the hill.

Okay. So what's actually happening in his body when he stops? Because it can't just be that he wakes up one morning in April and forgets how to eat.

No. And that's the most important thing to get across to Mark. These drugs work on appetite. They turn down hunger. That's the mechanism. Not a side effect. The mechanism. So the drug isn't teaching him anything. It's doing a job, every week, for as long as it's in him. Take it away and the job stops being done. As far as anyone can tell, the hunger comes back to somewhere near where it was. And his body's now lighter, which means it needs a bit less food to run. So he's hungrier. And he needs less. That gap is where the weight comes back from. It's not a character flaw. It's arithmetic with a hormone in it.

Which is a good line, and I'll probably steal it. But how do we actually know it's the drug? And not just people giving up once the clinic stops ringing them?

Because somebody tested exactly that. STEP 4. Everybody got semaglutide for twenty weeks first. Then they were split at random. Some carried on. Some were switched to dummy injections without knowing. And both groups kept the same lifestyle support — same advice, same programme. So the only thing that changed was the drug. In that trial, people switched to placebo put back six point nine per cent of their body weight, while the ones who stayed on lost another seven point nine. Same support. Same kind of people. Opposite directions. So when Mark worries the regain will be because he's weak — no. The trial took willpower out of it. And the weight still moved.

Is that just semaglutide, though? Because there's the newer one everybody keeps talking about, and I suspect Mark's mates at the depot are on that one.

Tirzepatide. And it's the same shape, just bigger. SURMOUNT-4 did the same kind of experiment. Everybody took it for about eight months and lost a lot. Then they were split at random, and one group was switched to placebo without knowing. And the people switched to placebo regained fourteen per cent over the following year. That's a big number. But here's the part that gets left out. Even after that, the placebo group were still nine point nine per cent below where they'd started the whole trial. So the regain was large. And it wasn't a full return. Not inside that year, anyway.

So each of the trials gives you one piece of it, with one drug, in one set of people. Has anybody actually put them all together?

Yes. And this is the strongest evidence we've got on the question, so it's worth taking slowly. There's a systematic review in the BMJ from January this year. It pulled together dozens of studies — trials and observational ones — covering more than nine thousand people who'd stopped a weight-loss medicine. And the headline is a rate. Not a verdict. The review found weight came back at about four hundred grams a month on average. Which, carried forward, gets people back to where they started. The review projected a return to baseline weight about a year and eight months after stopping. That's a projection, I'd stress. A line drawn forward from shorter follow-up. Not a year and eight months anybody actually watched. And for the newer drugs — semaglutide and tirzepatide — it was quicker. The review puts it at about eight hundred grams a month, with a return to baseline projected at eighteen months.

That's bleak, though, isn't it? The newest drugs, the ones everyone's excited about, and the weight comes back twice as fast when you stop?

It sounds bleak. But there's a reason it's faster for those drugs, and it's not a bad reason. They take more weight off in the first place. And the review found that bigger weight loss led to faster regain, whatever the method. You've further to come back from. So the newer drugs aren't somehow worse to stop. They've moved people further. Which also means the eighteen months is a projection for the average person in those studies. Not a countdown on Mark.

What about compared with dieting, though? Because Mark's done diets before. Plenty of them. And he'll tell you he always put that back on too, so what's the difference?

He's right. He did. Everybody does, to some degree. But the review compared the two directly, and the answer isn't flattering to the drugs. Weight came back faster after stopping medication than after a diet-and-exercise programme ended — by about three hundred grams a month. After a behavioural programme, the review predicted weight would return to baseline after about three point nine years. After the drugs, a year and eight months. Now — fair's fair — the drugs had taken off more weight in the first place. But the review says the regain was faster even allowing for that. And I'd guess the reason is the one we started with. A diet changes things he does. The drug changes how hungry he is. Stop a diet and some of the habits linger. Stop the drug and the hunger simply comes back.

And the blood pressure tablet? Because if I were in his shoes, that's the bit I'd actually be lying awake about. Not the trousers.

That's the right thing to lie awake about. And it's the bit that gets the least attention. Because the weight isn't the point. The weight is a route to the point. The point is his blood pressure, his blood sugar, his joints, his heart. And those follow the weight. In both directions. In the STEP 1 extension, the heart and metabolism improvements drifted back toward where they'd started, for most of the measures. And the BMJ review projected that every cardiometabolic marker it looked at would be back to baseline within one point four years. So the practical message for Mark is concrete. His tablet was halved because his blood pressure came down. If the weight comes back, his blood pressure may well come back with it. And nobody's going to notice unless somebody measures it. So that goes straight on his list. Blood pressure checked in the months after stopping. Not at next year's review. Sooner.

Which brings up the question I think Mark's really asking at two in the morning. Was it worth it? If most of it comes back, did he just waste two years of injections?

No. And I'd push back on that quite hard. Think about what the two years actually were. Two years of lower blood pressure. Two years of less weight on his knees. Two years of a body under less strain. Those happened. They don't un-happen because the weight drifts back later. And the trial gives a little more than that. Even a year after stopping, the STEP 1 extension reports that the semaglutide group kept a small improvement in blood sugar compared with the placebo group. Small. But real. And remember where they finished on weight. Still lighter than when they began. So it's not a choice between keeping everything and wasting everything. Most people land somewhere in between. And somewhere in between is a lot better than nowhere.

Which makes me wonder why the NHS stops it at all. If everything drifts back when you stop, why is there a two-year limit? It seems almost designed to waste the first two years.

It's a fair question. And the answer's partly money and partly how the drug was approved. NICE's guidance on semaglutide for weight says a maximum of two years, within a specialist weight service. That's where Mark's letter comes from. It isn't his clinic being mean. It's the rule his clinic works under. And there's a slightly awkward detail inside it. When NICE did the sums on these drugs, it assumed weight would come back over two to three years after stopping. The BMJ review points out that its own data suggest regain happens faster than NICE assumed. So the sums behind the limit rest on an assumption the newer evidence doesn't quite support. That's not a reason for Mark to panic. It's a reason the rules may change. But he has to plan for the rules as they are.

And there's a rule at the other end too, isn't there? I've seen something about stopping early if it isn't working.

Yes, and it's worth knowing, because it's the opposite situation. The same guidance says consider stopping if less than five per cent has come off after six months. The idea's simple. If the drug isn't doing much for you, you carry the side effects and the cost without the benefit. That doesn't apply to Mark. He's done well. But it explains why the whole system is built around stopping. It was designed with time limits from the start. What it hasn't really built is the bit after.

So he's being told to stop. He knows it'll probably come back. Is anyone actually supposed to help him with that, or is it just a letter and good luck?

Somebody is. And this is the part I most want Mark to hear, because it's a thing he can actually ask for. NICE's obesity guideline has a recommendation that's one sentence long. It says offer support to help maintain weight loss to people who are stopping weight management medicines. That's it. One line. But it means support at the point of stopping is something the guidance expects to happen. Not a favour. An expectation. So when Mark goes to his last clinic appointment, he can ask directly. What support do I get after March? Who do I see? Is there a dietitian, a group, an exercise referral? Some clinics will have a good answer. Some won't. But he should ask before the last appointment. Not after it.

And if the answer he gets is a leaflet and a "best of luck", which I suspect it sometimes will be?

Then he knows where he stands. And he plans around it. Which is better than finding out in May. But I don't want to make this sound like it's all down to the clinic. Because there's one piece of evidence I think matters more to Mark than any of the rest. And it's about something he can start doing this week, without anybody's permission.

Go on, then. You've been sitting on this one. What is it?

Exercise. And not in the vague "stay active" sense. There was a trial in Copenhagen. People with obesity lost weight on a short low-calorie diet first. Then for a year they were randomly given one of four things — a drug from the same family called liraglutide, a supervised exercise programme, both together, or a placebo. And then — this is the clever bit — everything stopped, and they were checked again a year later. A year after everything stopped, the people who'd taken liraglutide alone had regained six kilos more than the people who'd done the supervised exercise. And the exercise group's weight held. The trial reports that body weight was maintained a year after the supervised exercise ended. That's the thing I'd want Mark to sit with. The exercise kept working after the programme stopped. The drug didn't.

Why would that be, though? I'd have assumed stopping exercise would be just as bad as stopping the drug. You stop doing it, the effect stops.

You might think so. But exercise isn't only a treatment. It's a habit. And habits outlast programmes. When the drug stops, there's nothing left behind. The hormone's gone. When a supervised programme stops, the person has spent a year learning to do something. Some of them keep doing it. And in that trial, they did. A year later, the people who'd exercised were reporting far more activity than the ones who'd only had the drug. So the programme ended. The behaviour didn't. And that's the shape of the whole answer for Mark. The drug is something done to him. The exercise is something he does. Only one of those carries on after March without a prescription.

I'd want to know how much exercise, though. Because "do more exercise" is the advice everybody nods along to and then completely ignores. What did they actually do?

The trial was specific. Supervised group sessions twice a week, plus exercising on their own twice a week. And it wasn't gentle. The group sessions were hard indoor cycling and circuit training. So that's a real commitment. Four sessions a week. I don't want to pretend it's a stroll round the block. But I'd also say to Mark — he doesn't have to arrive at four. He has until March. If he starts with two this month, he's building the habit while the drug's still holding his appetite down. That's the best possible time to start. He's lighter. He's less hungry. And he's got a deadline.

And how far should we trust it? Because one trial, in Copenhagen, with an older drug, is still one trial. I don't want Mark hanging everything on it.

Neither do I. So here are the limits, plainly. It used liraglutide, which is an older daily injection, not semaglutide. And it was small — about a hundred people came back for the final check. And the people who came back had done better during the treatment year than the ones who didn't. The authors say so themselves. They tried to correct for it statistically, but it's a real weakness. So I wouldn't tell Mark exercise guarantees anything. What I'd say is that it's the best-supported thing he can do. The downside is close to zero. And it helps his blood pressure and his heart whatever the scales say.

Okay. So that's the evidence. But I want to talk about how this actually feels, because I suspect that's the hard part for him. Harder than any of the numbers.

It is. And I think there are two feelings in it. The first is dread. He's watched himself lose three stone. He's bought new trousers. People at the depot have said things. And now there's a date on the calendar when the thing that made it possible stops. That's a real loss, and he's allowed to feel it. The second feeling comes later, if the weight starts creeping up. And it's shame. Because he's been here before, with diets, and he's going to hear the old voice saying he's failed again. So I'd want him ready for that voice before it arrives. If the weight comes back, it's because the drug stopped. That's what the switch-to-placebo trial was built to test. It isn't a verdict on him.

And other people? Because someone's going to say something. Someone always does, usually at a family do, usually with a plate in their hand.

Someone will. The "well, you cheated anyway" comment. Or the quieter one — somebody noticing he's put a bit back on and not saying anything, very loudly. And the thing I'd want Mark to know is that a lot of people who make that comment are working from the same wrong sentence he found online. They think the drug was a shortcut, and the regain proves it. It doesn't. It was a treatment for something long-term, and when you stop treating a long-term thing, it tends to come back. That's not cheating. That's how long-term conditions work.

Is "long-term condition" fair, though? Calling it chronic sounds like a big claim. Are we just being kind to him?

It's the word the researchers use. The team behind that first trial we talked about wrote that their findings confirm the chronicity of obesity, and suggest ongoing treatment is required to maintain the improvements. And I find a comparison helpful. Nobody's surprised when blood pressure goes back up after stopping blood pressure tablets. Nobody calls that failure. Mark has two conditions he's been treated for. His weight and his blood pressure. When the tablet was halved, everyone said well done. If the weight comes back after stopping, the same logic applies in reverse. He didn't fail. The treatment ended.

Which raises the obvious question. If it's long-term, why not just stay on it? Could he pay for it himself, privately?

He could. Some people do. And I don't want to be squeamish about it, because it's a reasonable choice. A private prescription means carrying on. And carrying on is what kept weight off in the trials. In STEP 4, the people who stayed on kept losing. So did the ones who stayed on tirzepatide. So it works. The question is cost, and that's his decision, not ours. It's a monthly bill with no end date. For some people that's affordable and worth it. On a bus driver's wage, it might well not be. I'd just want him to make it as a decision, with the numbers in front of him. Rather than drift into it in a panic in April.

What about tapering? Coming down slowly instead of stopping dead in March. I've heard people swear by it.

I've heard it too. And here's where I have to stop short. It's not something any of the sources we've used tested. None of the trials we've talked about compared tapering with stopping. So I can't tell him it helps, and I can't tell him it doesn't. It might be worth asking his clinic how they handle the last few months. Some may step the dose down. But it should be a conversation with them, based on what they've seen. Not something he works out from a forum at midnight.

Fine. So once he's actually off it — April, May — what does he watch for? How does he know if it's going wrong before it's gone badly wrong?

The scales. But used properly. Not every day, because daily weight bounces around with water and salt, and it'll drive him mad. Once a week. Same day, same time, before breakfast. And — this is the useful bit — he picks a number in advance. Say, half a stone above where he stops. If he crosses it, that's not a crisis. That's a trigger. It means he books an appointment with his GP. Not to be told off. To have a conversation about what's next, while it's still a half-stone conversation and not a three-stone one.

Why decide the number in advance, though? Why not just keep an eye on it and see how it goes?

Because "see how it goes" is how half a stone becomes two. Weight comes back slowly. Four hundred grams a month is nothing you'd notice in a mirror. You'd notice it in a year. And by then the conversation's harder, because there's more shame in it and more weight to talk about. If the trigger's decided now, while he's calm, it stops being a judgement and becomes a rule. He doesn't have to decide whether it's bad enough. He already decided. Back in October, when he was thinking clearly.

And say he does cross it. It's June, he's half a stone up, he's sitting in front of the GP. What actually happens then? Is there anything left to offer him?

More than one thing, though I won't pretend there's a single standard answer. It depends where he lives and what his local services look like. But there are real options. Support he didn't take up the first time. A referral back into a weight service. A frank talk about whether paying privately makes sense. And a check that his blood pressure hasn't crept up while nobody was looking. What matters is that he walks in with half a stone, not three. Because at half a stone, every one of those options is still open. And the conversation's about what to do next. Not about what went wrong.

And food? Because when the hunger comes back properly, that's the actual fight, isn't it? Not the gym. The fridge at ten at night.

It is. And I don't think pretending otherwise helps. His appetite will come back. Probably not all at once, but over weeks. And the habits he's built on the drug — smaller portions, leaving food on the plate — were easy because the drug made them easy. They'll get harder. So the thing I'd suggest is practical rather than heroic. Use the next few months, while it's still easy, to find meals that fill him up without much in them. Protein. Vegetables. Food with some bulk. If he works out a handful of those now, they're there when the hunger returns. So he's not inventing a diet under pressure in April. He's carrying on with meals he already knows work.

Does it matter who else is in the house? I'm imagining Mark's got a partner who's been cooking around the drug for two years.

It matters. A lot. And it's something nobody puts in a guideline. Say his wife, Sue, has been doing smaller portions, because that's what he could manage. When the drug stops, the easy thing is for the portions to drift back up, without anybody deciding they should. So it's worth the two of them having that conversation now. Not as a diet. As a plan. What do we keep? What's the Friday night thing we're both going to miss? Which meals do we make bigger and which do we leave alone? That's a ten-minute chat at the kitchen table. And it does more than any amount of willpower in April.

That's a lot to get done before March. Is there an order to it, or does he just try to do everything at once?

There's an order. And I'd keep it short. First, the conversation with the clinic — what support exists after March, and how they handle the end. Second, the exercise, because it takes longest to build and it's the thing that seems to outlast the drug. Third, the blood pressure, because that's the thing that actually matters for his health, and nobody will check it unless he asks. And then the trigger weight and the meals. None of those need a prescription. All of them can start this month.

So bring it back to him, then. It's Monday morning. The letter's on the side. What does Mark actually do?

He rings the clinic and books a proper conversation about stopping. Not a quick check. A conversation. He writes down three questions before he goes in. He looks up whether there's an exercise referral scheme or a gym class near the depot, and he goes twice this week. Not four times. Twice. He asks the practice nurse to put a blood pressure check in the diary for a couple of months after March. He has the kitchen-table chat with Sue. And he weighs himself, writes it down, and adds half a stone. That's his number. And then he stops reading the internet about it. Because he's found the sentence that frightened him. And now he knows which half of it was true.

And the sentence itself? The one he found that night? Where does it end up?

Partly right. Most people do regain most of it over a year or so. But it wasn't all. It wasn't everybody. And it definitely wasn't nothing-you-can-do. The regain is the drug stopping, not Mark failing. And the one thing that held up after treatment ended, in the exercise trial we talked about, was the thing he can start today. Moving more, and making it a habit.

Before we finish, what don't we know? Because you've been careful to keep that line drawn, and I'd like you to draw it.

Three things, mainly. The first is time. For the newest drugs, there's very little follow-up after stopping. The BMJ review says the data for the newer drugs were limited to only eight studies, with a maximum of twelve months' follow-up after stopping. So anything beyond a year is projection. And that matters, because nobody knows whether the weight keeps climbing all the way back, or levels off somewhere below where people started. The STEP 1 authors say they can't tell whether the slowing they saw was a plateau, or just weight getting close to where it began. The second gap is real life. Almost all of this comes from trials. Trial participants are carefully chosen and closely followed. The review itself says estimates from routine practice are needed. Mark's NHS clinic isn't a trial, and his experience could be better or worse. And the third is what happens if people stop and later restart. That's going to be very common. And it isn't something the sources we used tested.

If Mark takes one thing away from all of this, what do you want it to be?

That the weight coming back after stopping is the expected result of a treatment ending. Not proof that he failed. It's likely. It's usually not all of it. And it's slower than the panic makes it feel. And between now and March, he's got one thing that seems to last beyond the prescription. He should start it this week.

And three things to take to his doctor, or to that last clinic appointment.

First. What support will I get after I stop, and who do I contact if the weight starts coming back? He's entitled to ask that, and NICE backs him. Second. Should my blood pressure be checked after I stop, given my tablet was reduced? Ask for a date, not a "we'll keep an eye on it". Third. If my weight goes up by a set amount, what are my options — including carrying on privately, or anything else the clinic can offer? Asking that before March, rather than after, is the whole point. Because the worst version of this isn't the weight coming back. It's the weight coming back while everybody, Mark included, pretends it isn't happening.