Drugs like semaglutide and tirzepatide are “a major leap forward” in treating obesity, but they’re not magic bullets, says James Hill, PhD, a professor of nutrition sciences at the University of Alabama at Birmingham (UAB).
Hill, who has more than 40 years of expertise in obesity treatment and serves as director of UAB’s Nutrition Obesity Research Center, says we do know some things about what happens when patients stop taking these drugs, but that much more research is needed. His forthcoming book on the subject, tentatively titled The Transition Diet, is slated for publication next year. He sat down with WebMD to discuss life after getting off the drugs.
Read more here about life after GLP-1 drugs like Ozempic.
Editor’s Note: This interview has been edited for length and clarity.
WebMD: What happens when patients stop taking GLP-1 receptor agonists, or GLP-1s, such as semaglutide (Wegovy and Ozempic) or tirzepatide (Zepbound)?
Hill: Most people regain the weight. The drugs are very powerful. They really reduce your hunger. They also reduce food noise. Whether that's for a short period or long period, the effects the drug has on hunger, appetite, food noise – those go away, so you're right back where you started.
WebMD: Can you explain food noise?
Hill: The food noise is terribly interesting. I didn't think much of the term when I first heard it, but since then, so many people tell me it describes exactly what's happening. The concept of food noise is you're spending a lot of conscious energy thinking about food. You may be thinking, “I know I've got chips in my pantry,” or “What am I going to have for dinner?” or “Am I going to be able to eat healthy this weekend?” There's a lot of noise in your head that relates to food.
When people are taking these medications, they report that that goes away. For some people, that's hugely powerful. Now, a lot of people probably can't relate. Someone suggested we need a pill so that people who don't experience food noise could experience it and see what it's like, but (blocking food noise) seems to be a very powerful, positive effect of the medications.
WebMD: How does the body adjust to quitting the drugs? Is there a metabolic backlash or spike in hunger?
Hill: I'm not sure we really know. I suspect it differs from person to person. When you stop the drug, it's going to be in your system for a while. It isn't like, boom, I stopped the drugs and now I'm going to go on a food binge. I haven't seen any data to suggest hunger spikes more than before – but it goes back to before. Obviously, people that have problems with obesity had those issues beforehand. When you stop the drug, you're right back where you started.
WebMD: Is weight management after GLP-1s different from normal weight management?
Hill: It's different in the short term, not in the long term. You have to deal with that transition period when you go off the drugs because, again, you're going to get a pretty big increase in hunger, maybe a decrease in satiety [a feeling of fullness and satisfaction], maybe an increase in food noise. Those things can cause you to gain a lot of weight if you aren't ready for them. Once you get through that transition, I think it's the same ways to keep weight off.
WebMD: Are there best practices for weight management after you stop using GLP-1s?
Hill: In the media, you can find a lot of people telling you what to do. The problem is those things aren't very science-based. What people are suggesting is you basically eat a healthy diet, a lot of fruits and vegetables, avoid processed foods, etc. Well, guess what? That's the same advice people were getting beforehand when they couldn't manage the weight.
It's not easy because you have to find a lifestyle that in some ways takes the place of what the medications were doing for you. I don't think we're giving people good advice on how to keep the weight off.
WebMD: What is the best diet after stopping GLP-1s?
Hill: That's not the most important factor. I don't think we've yet identified the best diet post-medications. I think there's going to be more research. You've got to look at how your metabolism may be better geared up to help you keep the weight off. I think there are several diets that can be helpful. Look for a diet that replaces some of the positive effects of the drugs – such as satiety. What are things in the diet that promote satiety? Well, fiber, protein – there may be other things.
There's the other side of the coin, too: I think physical activity is absolutely essential for keeping weight off. You don't have to be physically active with the drugs because they do a lot of the things that physical activity can do. But to keep weight off, it's not just diet. It's physical activity.
The other part is the mental aspect – that mindset, how you think of things, how you handle challenges, how resilient you are, etc.
WebMD: Is it helpful to boost your activity level while you're still on the drugs? Does that help you transition?
Hill: At least one study shows exercising while you're on the medications can produce a little more weight loss – not a lot, but a little bit more. The other reason that I would say to exercise – if you're planning to come off the medications – it gets you to a level where you're better able to maintain weight.
WebMD: You once said, “I think the way our bodies work best is when we're expending a lot of energy and we're eating a lot of energy. We never developed biological systems for food restriction. We developed biological systems to eat.” Why is that important for users of these drugs to understand?
Hill: Look at how we've tried to manage obesity for the past century, half century: By getting people to eat less. Eating less is a very effective strategy to lose weight. Just about every diet works if you follow it because you eat less. The problem is eating less is not a long-term solution because you get hungry. The reason you get hungry is because our bodies developed in a time when you had to do a lot of physical activity to get through the day, and the goal was eating enough to meet those needs.
Biologically, we developed systems to promote food intake, not a lot of systems to promote food restriction. I think we got it wrong. I think the goal in weight management is not to restrict what you eat. I think the goal is to eat a lot, and the only way you can eat a lot and not gain weight is to be physically active.
WebMD: A recent study shows most people stop using GLP-1s before their doctors recommend stopping. What are some reasons people quit GLP-1s?
Hill: First of all, side effects. For most people, the side effects are gastrointestinal. You feel full and nauseous, etc. While people are losing weight, they're pretty tolerant of those side effects, but everybody will stop losing weight on the drugs. You're going to reach a new steady state at a lower weight. It's more difficult to convince people to stay with it if they're having side effects during weight loss maintenance.
Another big reason people quit is availability. It's hard to find them, even if you have a prescription. A third reason is cost. These medications are expensive. If your insurance doesn't cover them, you might be out $1,000 a month.
We also find some people miss the enjoyment of food. Sounds a little crazy, but people oftentimes say, “For me, I don't care. I can eat or not eat.” Other people, their social life may revolve around food so much they miss food.
Finally, some people feel like they shouldn't have to take a medication forever. That's one where we tell people, “No, you're not cheating to take the drugs. In fact, it's helping you have a fair fight with your biology.”
If they take the medications and they work – you're happy, you feel good – there's no reason you shouldn't continue taking them indefinitely. For people who can't do that, I would like to help them with a strategy because stopping the drugs without a strong strategy is going to result in weight regain.
WebMD: How are insurers handling this?
Hill: Most insurers are trying to figure out how they handle this. One insurer told me if they covered everybody eligible, everybody’s premiums would go up significantly. For insurers, if the weight comes back when you stop the drugs – and most people are stopping the drugs – then as an insurer I would ask: Is the financial payoff, which is a long-term payoff, really there? I think it has some implications for reimbursement and for the long-term financial model.
WebMD: The side benefits include cardiovascular advantages. If you quit the drugs, are those advantages lost?
Hill: Huge point. I think these medications illustrate two important things: One is that weight is not just psychological. It's biological. We can't say you didn't lose weight because you don't have willpower or you didn't stick to your plan. There's huge biology at work.
The second thing is this shows how important weight loss is. As far as I know, most of the effects of these medications are the effects of weight loss. It suggests that if you produce the amounts of weight loss these meds can produce – and they're producing losses of 20%-25% of body weight – everything is better: Diabetes gets better. Heart health gets better. Kidney health gets better. It shows if we could as a population reduce weight, all those important things would come along.
WebMD: Is there evidence it's easier to follow healthy diet and exercise guidelines once the weight is off?
Hill: That's a question I'm interested in in my own research. Again, it's not one size fits all. My guess is there are going to be people who lose weight and can’t wait to get out and move. They're going to feel better, and others are not. We need to reexamine what success looks like. If you take these meds and you're not active, you don't worry so much about your diet -- is that success? Or is success having some level of fitness, being able to have functionality in your life, to be able to walk and so forth?
WebMD: You’ve been vocal about the quality of weight loss – namely, that while fat loss is generally good, too much muscle loss can be a negative effect. How do GLP-1s affect weight loss quality?
Hill: We don't know for sure that the medications are having a negative impact on body composition. Again, it's not one size fits all. I would like to see more data on older people. You don't want to lose body mass when you get older. To be fair, companies are doing this kind of research, so we're going to get the answer, but we need to know if there are populations that might suffer a greater-than-expected loss of lean body or muscle mass using the medications.
WebMD: Is there any research to suggest it’s unsafe or unwise to continue GLP-1s for weight maintenance indefinitely?
Hill: We don't have long-term data on their use with weight management, but the sense is they're probably going to continue to be effective. From everything we know, if you want to continue them sort of permanently, they're likely going to work. We still need data to prove that, but so far, there haven't been any red flags to say over time they quit being effective.
The drugs are kind of set up to take them forever. Most of my endocrinology colleagues would say they're like blood pressure or lipid or diabetes medications. You’ve got to take them for them to work, so you take them lifelong. I think that's OK – if people feel good, the drugs work for weight loss, they don't have problems with side effects – that’s a viable alternative.
WebMD: You’ve said these drugs are exciting, “a major leap forward,” but they're not magic bullets. Elaborate please.
Hill: Let me preface that to say this is one of the biggest breakthroughs that we've had in the obesity field. These are wonderful new tools. If you want to lose weight, these drugs can do it, but they're not the magic bullet. They're a part of the solution, and I think there's a lot of stuff we can consider with the meds.
Maybe you use them when you need them. Maybe you lose weight on the meds, you go off as long as everything's OK, and when things aren't OK, you go back on the meds for a while. Maybe we look at intermittent use or low-dose use. I think what we're learning is more and more how to use these tools.
