Daniel Lieberman: My real nightmare about GLP-1s is that we end up in a world where we cease to pay attention to the cause of the problem, which is the various reasons that people are struggling with obesity in the first place. It’s like in the supermarket aisle, you can go down one aisle of the supermarket, and there are the companies selling all these foods that are really bad for us. And then the same companies in the next aisle are selling us the weight-loss products that deal with the problem that they caused in the other aisle.

Laine Perfas: GLP-1s have evolved from a treatment of Type 2 diabetes into drugs for weight management, leading to a surge in usage and evidence of promise against a range of other health issues. But given how new these drugs are to the market, medical professionals are only now starting to figure out who should — and should not — be using them, considering downstream risks like muscle loss, which can particularly impact the elderly.

They also raise the question: Do we lose anything when we allow taking a pill to become a substitute for lasting lifestyle changes?

Welcome to “Harvard Thinking,” a podcast where the life of the mind meets everyday life. Today, I’m joined by:

Caroline Apovian: Caroline Apovian. I am an obesity medicine specialist, professor of medicine at Harvard Medical School.

Laine Perfas: She’s also the co-inaugural director of the Integrated Mass General Brigham Center for Weight Management and Wellness. Then:

Lieberman: Daniel Lieberman. I’m a professor of human evolutionary biology at Harvard University.

Laine Perfas: He’s also a bestselling author and recently published “Fed Up: What Evolution Reveals About Food, Diet, Health, and Eating Well.” And finally:

Fatima Cody Stanford: Dr. Fatima Cody Stanford. I’m an obesity medicine physician-scientist at Mass General Brigham.

Laine Perfas: She’s also an associate professor of medicine and pediatrics at Harvard Medical School.

And I’m your host, Samantha Laine Perfas. I’m a writer for The Harvard Gazette. Today, we’ll talk about GLP-1s and why we should be excited about their potential — and also cautious.

And a quick note, Caroline Apovian and Fatima Cody Stanford have worked with pharmaceutical companies, including makers of GLP-1s. Caroline worked as a former consultant and Fatima as a current consultant. Fatima has also received industry funding for her research.

What is so magical about this category of drug?

Apovian: The word magical is a very interesting word to use. We call these drugs game changers because of their robust effects on health and in particular on first, you’re right, Type 2 diabetes, and now obesity. Obesity affects 42 percent of the United States’ population. Fatima Cody Stanford was instrumental in getting organizations to distinguish obesity to be a disease and not a matter of willpower. And once that happened, the race was on to develop these drugs for use in obesity. And the reason why they’re considered magical is because, for the first time in many people’s lives, they take a GLP-1 and suddenly, as they say, the food noise is gone. They eat, they’re full, they feel like eating healthy food, and they feel like exercising. We’ve never had anything like this before to treat obesity, except for metabolic bariatric surgery.

Cody Stanford: I actually push back a little bit on the terms game changer or magical. I do think that they have definitely created an inflection point in how we think about this disease process. Their potency has changed how the world sees or approaches this disease process due to the fact that we’re looking at a total body weight change of either 15 percent or 22 percent, or if we’re looking at the triple agonist, you know, getting closer to 30 percent total body weight loss. When we look at these, people in the world are beginning to realize that this disease process is beyond this idea of willpower and self-control, that there is actual biology behind this disease. It’s not just “Oh, eat less and exercise more.” This inflection point of really thinking about this from a disease process, while we can go back to the AMA declaration in 2013 or the World Medical Association, which just happened in 2025, it’s when people start to become acclimated to the utilization of these medications and say, “Wait a minute, I do feel different. Wait a minute, I am making different choices. Wait a minute, these choices are influencing the way I interact with the world around me,” that they begin to think, “Wait a minute, it must be something in the biology of me and how my biology may differ from those around me.” And that was what really got the conversation moving in a different direction outside of the typical status quo conversation.

Lieberman: If I can just add to that from an evolutionary perspective, I want to remind us all that we never evolved to lose weight. We’re an interesting species. Human beings have a lot more body fat than most other mammals. Most mammals rarely have more than about five percent body fat. But in our evolutionary history, we evolved to put on a lot more fat because it’s really important for feeding our brains, for our reproductive system, for all kinds of reasons. You know, in the past, it was extremely rare that anybody could gain extra weight, and we never evolved adaptations to lose it. And instead, the key adaptations that we have are hunger and appetite, right? So when we lose weight, we go into what we call negative energy balance. We turn on a whole suite of signaling molecules, hormones that signal to our brain that we’re losing weight and make us hungry. That’s why it’s been so hard for so many people for so long to lose weight, because they’re fighting against millions of years of deep and fundamental adaptations. And all of a sudden, for the first time, we’ve got this drug that can turn off some of those adaptations. From an evolutionary perspective, this is really quite astonishing.

Apovian: The reason why I think these are game changers for the field of obesity medicine is because these are not drugs. These are analogs of the hormones that the body makes when you eat food. They have numerous effects on other organs, including the brain. I’d love to know from you, Dan, what you think about this evolutionary process and using these naturally occurring hormones to then counteract what we’ve done to the environment. Because it can’t be purely genetic, because our genes have evolved over millions of years and not over 50 or 100 years. What is it about the environment? Is it the ultra-processed food? Is just the fact that we’ve got all kinds of ways to throw down 3,000 calories by rolling down our window at fast-food restaurants?

Lieberman: Look, everything about our bodies is an interaction between our genes and our environment. Everything, right? This is no exception. But as you say, our genes haven’t changed that much in the last few generations. But in my lifetime, the percentage of Americans with obesity has quadrupled. Obviously, it’s not because some genes for weight gain have suddenly swept through the population in the last generation or two, but it is true that some people have more proclivity than others. The other thing is that, of course, there are many factors that affect weight gain. Your microbiome is one of them; your metabolism. People differ in their metabolic rates. Physical activity has some effect, particularly for weight gain prevention, not so much for weight loss. We could go on for all the various factors, but nobody doubts that the one thing that’s changed the most, of course, is our food. When we walk into a supermarket here in Boston, the average supermarket here has 40,000 different kinds of food — 40,000 different kinds of food, and something between 50 percent and 70 percent, depending upon your definition, are ultra-processed. These are foods where the fiber’s been removed; sugar and fat has been added; they’ve been made hyper-palatable. They’ve got all kinds of tricks and gimmicks to make us eat more. There is an association unquestionably between the proliferation of processed foods and weight gain. And here’s the thing: Most of us, once we gain the weight, because of those adaptations, our bodies then reach a new set point. We now call it a settling point, because for reasons that I don’t think any of us understand, your body fights to put you back at the previous weight, not necessarily your original.

Cody Stanford: One of the things that I want to bring up, particularly as we think about this from an evolutionary perspective, is I want to think about the group that happens to carry the highest weight, particularly within the U.S. population, which happens to be Black women. I want to take us back to our period of enslavement. And if we really look at when Black women started to accumulate great levels of adiposity, it was actually during our periods of enslavement, which is very interesting because during the period of enslavement, we didn’t have ultra-processed foods. There were high levels of physical activity. But what we don’t account for during that time frame, which really sets us up for the high levels of obesity within this population, the group that I represent, is the allostatic load and stress that started to occur for that population at that time. We have to recognize that early predisposition to obesity within the population that carries the highest burden here in the United States now, and when it started for us, and then bring it over to the high burden that then exists, and particularly think about it now in the context of what we see.

Lieberman: I completely agree. To add to that list, I should have mentioned stress, chronic stress, for example, which is, of course, a function of socioeconomic status and racism. There are epigenetic effects. I 100 percent agree with you. This is a multifactorial problem. There’s no question that our food supply is a major one, but it’s not the only one.

Laine Perfas: One thing about food that I did want to ask about was this idea of food noise. What does that mean, and what is it about GLP-1s that are affecting it?

Cody Stanford: For people who have food noise, they are constantly thinking about food. It doesn’t matter if it’s ultra-processed, it doesn’t matter if it’s not. They have this constant desire to want to eat. For those who are responders to GLP-1s, when they go on something like a GLP-1, they say they no longer think about eating in the way that they did before. That volume that might be really high, you turn that down and they’re like, “Wait a minute, I’m not thinking about food. I actually forgot to eat breakfast, lunch, and wait a minute, it’s dinner time.” I turned down the volume. This thinking about food, it’s no longer a focal point.

Lieberman: For some people, not everyone, GLP-1s also reduce other kinds of noise, other forms of addiction for people who have issues with, say, tobacco or certain pharmaceuticals or alcohol. There’s something just really quite extraordinary about this hormone and its multiple effects. You have to remember that hormones evolved to do multiple things, but I like to think of hormones really as allocators of investment and energy. This is a hormone that’s basically telling the body to turn down stuff. We have hormones that turn things up and hormones that turn things down. It’s a very crude simplification. But what’s amazing is that GLP-1s, normally in human beings, they have very short action. The real turning point for this was that they used essentially the GLP-1 of a lizard that eats only once every three weeks or something. I can’t remember. The Gila monster. That has a much longer-acting effect than the human version. Now we’re finding out all kinds of fascinating things about this hormone.

Laine Perfas: One thing I want to talk about too is that the usage for these drugs has increased significantly. I think as of last year, one in eight American adults was using GLP-1s for weight loss. Dan, you have been vocal about some of your skepticisms with GLP-1s. I would love to hear some of the concerns and/or limitations that we are seeing.

Lieberman: I’m not skeptical. I have two concerns really that are overriding. The first is that the evidence is that a lot of people on GLP-1s are losing a lot of muscle mass. As with bariatric surgery, where you have very extreme weight loss, people can lose something like 20, 30, even more percent of their body weight, and a large percentage of that, maybe up to 30 percent of that, can be fat-free mass. We’re not talking about body fat; we’re talking about other tissues, and some of that’s muscle. One of the big issues for aging in the United States is sarcopenia, which is age-related muscle loss. So it’s not a skepticism, but it’s a concern that individuals who are on GLP-1s and losing a lot of weight, if they don’t include some degree of strength training, they could be at greater risk for age-related muscle loss, for sarcopenia. And that’s really concerning because that becomes a kind of vicious cycle. Once you get very frail, you become less physically active. You become less physically active, you become even less active. I can speak from personal experience with my parents: It’s a challenging thing to watch.

My other concern, of course, is that a lot of people, and Caroline and Fatima will know the data better than I, but there’s a fairly high quit rate for these drugs. I think the latest study I saw, and I’m sure there’s better data now, was that over 50 percent of people are quitting it between one and two years. And then the other concern is what happens when they quit, right? Are they gaining the weight back? But you guys know more about this than I do.

Apovian: These are two big areas, Dan. The muscle-loss concept is very much debated. First of all, when you lose any kind of weight by any means, you’re right — bariatric surgery, drugs, diet, and exercise — you don’t lose just fat, right? Because if you have obesity, there’s extra muscle to hold everything together. And the Krebs cycle, metabolism, you need amino acids to burn energy, so you can’t just lose fat. There is always a certain percent that is muscle, and you really can’t go below losing 20 to 25 percent of the total as muscle. So that’s physiology. Yes, there are people who lose more, 30 or 40 percent. We think it may have to do with the rapidity of the weight loss, if they’re not eating enough protein, and yes, if they’re not doing strength training. But I think that the largest concern about muscle mass should be with the older population. The older population is already losing muscle mass at something like 1 percent per year after the age of 40 or 50. And yes, those people on GLP-1s or after bariatric surgery may lose more muscle mass and develop dysfunction and frailty and sarcopenia and also bone loss. So that’s a valid concern, and we’ve already had people in the older population losing 40 pounds on Wegovy and then falling and fracturing their tib-fib because it was fragile.

Cody Stanford: The muscle loss piece is by far more germane to those that are older adults. And particularly with the new Medicare Bridge program that’s just come into place. For those who are unaware, Medicare has decided to start covering these medications for individuals with obesity as of July 1st, which means that there’s going to be a sizable percentage of the population who now have access to these drugs. The program appears to be in place from July 1st of 2026 through December 31st of 2027. We have no idea what’s going to happen after that, but a sizable percentage of the population, particularly those who are 65-plus, will gain access. Now, we also know that population has a higher tendency to have issues like sarcopenia, and we do need to think about protein and muscle retention for that population.

And so this is what I really like to emphasize with my patients, and this is how I bring them into the conversation regardless of age. I say in our 20s and 30s, I like to think of a one-to-one ratio of cardio to strength, so 30 minutes of strength for 30 minutes of cardio. And when we get into our 40s and 50s, where I exist, in that middle-age range, I think of it as a two-to-one strength to cardio ratio. So for every 60 minutes of strength, 30 minutes of cardio. In our 60s and 70s, I like to think of a three-to-one strength to cardio ratio. So for every 90 minutes of strength, we should have 30 minutes of cardio. And if we get into our 80s and 90s, I like to think of it as a four-to-one strength to cardio ratio. So for every hundred and 20 minutes of strength training, 30 minutes of cardio. Now, tell me how many people actually do that.

Apovian: Zero.

Cody Stanford: Exactly. Unless you’re me, right? So this is what I emphasize with my patients. And when they’re getting that mantra, they begin to realize the importance of strength training. Because we’ve been fed this idea that it’s cardio, cardio, cardio, cardio, cardio. But if you’re really strength training in the way that we’re talking about it, you are getting that heart-health benefit from doing the strength training. Now, moving into your second piece, which is how people pull back the utilization. So 50 percent discontinuation of GLP-1s. The number one reason for the discontinuation is cost, access. But what we’ve seen, and I will use Massachusetts as a case in point for discontinuation for these medications, up until January 1st of 2026, Massachusetts had the best utilization and coverage for GLP-1 receptor agonists. If we look at employer-sponsored insurance here in Massachusetts, the big four are Mass General Brigham, Harvard Pilgrim, Tufts, and Blue Cross Blue Shield of Massachusetts or New England. All of these insurers were covering GLP-1s for patients with obesity. But as of January 1st, they pulled back coverage for this patient population.

What happened was our patient populations got pulled off of these medications. Now, for persons who are high-income earners, they were able to retain utilization of these medications. Price point: between $300 and $450 a month out-of-pocket price. But if you’re a high-income earner, that’s not too much for you. If you’re not a high-income earner, it’s a lot.

Apovian: That’s a very important point. I just saw a patient virtually because he weighs 625 pounds. But he did weigh 725 pounds, and he lost 100 pounds getting ready for bariatric surgery with Zepbound. He lost 100 pounds on the top dose of Zepbound, and then in July it got pulled. He is now gaining weight. And I just messaged the surgeon and said, “You better get him to surgery now because he’s going to gain that weight back. You got to get him to surgery now.” This is the segment of the population, BMI over 60, still rising exponentially in the United States and probably worldwide. So what are we going to do about this weight regain? It’s causing a lot of oxidative stress, especially as you gain it rapidly. So that food noise comes back very aggressively, especially if you’ve lost 100 pounds and you suddenly stop the GLP-1. You suddenly think that you’re starving to death.

Lieberman: My other concern about GLP-1s is about prevention, and it really goes back to what we started off talking about, which is that — so I have this term I apologize for, which I created, called dis-evolution: When we treat the symptoms rather than the causes of a mismatch problem, then we just keep the cycle going. My real nightmare about GLP-1s is that we end up in a world where we cease to pay attention to the cause of the problem, which is the various reasons that people are struggling with obesity in the first place. It’s like in the supermarket aisle, you can go down one aisle of the supermarket, and there are the companies selling all these foods that are really bad for us. And then the same companies in the next aisle are selling us the weight loss products that deal with the problem that they caused in the other aisle. Ultimately, what we should all really want to do is prevent this problem from happening in the first place.

Laine Perfas: That got to another question that I wanted to ask all of you. It is amazing that these medications are able to so effectively help people. And also, what happens when it becomes a substitute for the lifestyle change that needs to happen?

Cody Stanford: I don’t think it’s a substitute for the lifestyle changes. By the time the patients get to us, these patients have tried and failed, or that lifestyle has tried and failed them. They can list 25 to 30 different programs that they’ve tried and failed. It’s like the Biggest Loser concept. It worked for a short period of time, and then it didn’t work, and their bodies came back. And so then they’re coming to us because they’re like, “OK, look, I’ve tried all these things.” Let’s say they go on these medications and they’re like, “Oh, wait a minute, this works.” Now they can actually go work out; they are feeling good about themselves, going to the gym, and seeing the results pay off while they’re on the medications. Because as Dan mentioned, if it pulls back, they’re regaining, and then they’re feeling lack of confidence. Their self-worth and self-esteem unfortunately deteriorate because they’re like, “Here I am. I finally got to the quote-unquote ‘promised land,’ and it was snatched from me.”

Apovian: I always say nobody wants to have obesity. If diet and exercise worked, and they wouldn’t be stigmatized walking down the street because they have obesity, they would have done it. We have a disease. GLP-1s are not removing the cause of the problem. But what it is doing is it is reducing the body weight set point.

Lieberman: I fully agree with you two, but I do want to ask you about children. As I’m sure you both know, there are very scary statistics about the percentage of teenagers in the United States who are classified with obesity. It’s somewhere between 20 and 30 percent, depending upon which study you believe in. Should we be giving GLP-1s to those kids? Me, my concern is, how do we prevent those kids from getting into that problem in the first place?

Cody Stanford: I treat the full age spectrum, my patients go from 2 to 90-plus, and I think about, who are the pediatric patients who actually end up in my clinic? It’s usually the children of my patients. How do I prevent this? If I can get the patients modified preconception, I have a higher likelihood of having children who have a lesser likelihood of obesity. The best study was a study that came out in the Journal of Clinical Endocrinology and Metabolism back in 2009, which demonstrated that children born to mothers who had undergone bariatric surgery had a threefold decrease in the likelihood of obesity in the mother after she had undergone surgical intervention. So if we can modify the weight status of the parents preconception, we can modify the children’s weight status.

But let’s come back to the question you specifically asked: Do we utilize these medications in children, and how does that work? I do treat patients as young as 12 with GLP-1 receptor agonists. What I have found in treating these patients, first of all, when I get pediatric patients, I find that they actually have health status that’s much worse than my adult patients. Their cholesterol is much worse. Their liver function tests are much worse. Their hemoglobin A1C, which is their blood sugar, is much worse. What I also find when using these medications is that they usually respond much better than my adult patients to the therapy when given to them. That gives them a likelihood of having a much better life moving forward than they did prior to the advent of these medications. I see these patients go from looking down in my visit, not actually making direct eye contact because their self-esteem, their value, their self-worth is so tied into their weight, to making eye contact, having an improvement of their cardiometabolic health, and allowing them to move forward into adulthood with a better life.

Laine Perfas: When we talk about GLP-1s, obviously they’re so new, we’re still figuring out so many things. What do you feel we are not talking about enough? Or what are things that we really should be focusing on as an area of further research?

Apovian: I think that GLP-1s just created this explosion in social media and in research and in the medical community. And I think what we’re not talking about adequately enough is, who are they for? The protocols are not in yet. We’re writing guidelines with the ADA, but we’re not categorizing patients. I think the highest-risk patients should be getting our more potent drugs and be considered for metabolic surgery. The BMI is not an adequate measure of body fat. We still don’t have the right tools to measure who is at risk. And social media now is on a rampage which compounded GLP-1s that people are taking to lose 10 pounds. If you take a GLP-1 to lose 10 pounds and you don’t have the disease of obesity, are you setting yourself up for stopping the medication, gaining even more weight back, and developing a problem that you didn’t have in the first place? If you’re going to take a GLP-1 just to lose 10 pounds so you can look good in your dress, you should not be taking a GLP-1. It’s not for you.

Cody Stanford: One of the key things that we’re not talking about are the potential use-case scenarios for GLP-1s. What we do know is the GLP-1s were initially approved for Type 2 diabetes, and then we moved into obesity and obstructive sleep apnea. But we’re going to continue to see different use-case scenarios for these medications, and there’s a variety of research interests that move outside of the space of cardiometabolic health into looking at rheumatologic conditions like gout and rheumatoid arthritis. We’re looking at disorders like Alzheimer’s disease and Parkinson’s and things of that sort. As we begin to see this blossoming of research, it’s going to be interesting to see how these medications begin to explode beyond the cardiometabolic use and then how the dosing structure will change to accommodate these potential use-case scenarios as we move forward.

Lieberman: My thing that I really hope we can use GLP-1s to talk more about is that they really are game changers for treatment. There’s no question about that. But they’re not game changers for prevention. Wouldn’t the best world be where you didn’t have to use these in the first place? The fact of the matter is we do, and we should, and they are helping a lot of people. And we’ll find out better ways to use them, and maybe other adjuvants that can help us use them better. But hopefully, we can leverage the opportunities that GLP-1s are giving us for treatment to also think more about prevention.

Laine Perfas: Thank you all for joining me for this conversation.

Lieberman: My pleasure. Thank you.

Apovian: It’s been a pleasure speaking to everyone.

Laine Perfas: Thanks for listening. For a transcript of this episode and our other episodes, visit harvard.edu/thinking. If you like this episode, rate and review us on Apple or Spotify, or like us on YouTube. It helps others find us. This episode was hosted and produced by me, Samantha Laine Perfas. It was edited by Ryan Mulcahy, Paul Makishima, and Sarah Lamodi. Original music and sound design by Noel Flatt. Produced by Harvard University. Copyright 2026.