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Obesity, weight loss treatments, set point theory & more with Fatima Cody Stanford, MD, MPH


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Fatima Cody Stanford, MD, MPH, MPA, MBA, an obesity medicine physician at Mass General Hospital and associate professor at Harvard Medical School in Boston, talks about redefining obesity as a brain disease rather than a consequence of poor health choices. American Medical Association Chief Experience Officer Todd Unger hosts.


  • Fatima Cody Stanford, MD, MPH, MPA, MBA, obesity medicine physician, Mass General Hospital and associate professor, Harvard Medical School in Boston

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Unger: Hello and welcome to the AMA Update video and podcast. Today we're talking about redefining obesity as a brain disease rather than a consequence of poor health choices. I'm joined today by Dr. Fatima Cody Stanford, an obesity medicine physician at Mass General Hospital and associate professor at Harvard Medical School in Boston, who is leading this charge. I'm Todd Unger, AMA'S Chief Experience Officer in Chicago.

Dr. Stanford, thanks so much for being here today.

Dr. Stanford: Thanks so much for having me, Todd. It's a delight to be with you.

Unger: Well, I've seen you all over the news in the past few weeks. I appreciate you taking the time to talk with us today. Well Dr. Stanford, let's jump right in here. Most of us have been given this message that if we eat right and we exercise and of course, have a decent amount of willpower, that we're going to be able to achieve and maintain a healthy weight. But your research has shown that the reason that some people can't lose weight may have more to do with brain chemistry than anything else. Let's talk about that.

Dr. Stanford: I think this is an extremely important question, Todd. I'm so glad that you asked this. And let me tell you, I was part of that camp that believed that it was just about how much exercise you did, how you ate. And I would even say this to my patients in the past without me understanding how complex the brain is in regulating our weight.

And I'm just going to talk about this in terms of two pathways. There's a pathway of our brain called the POMC pathway that tells us to eat less and store less. For people that signal really great down this pathway, they tend to be very lean, not struggle with their weight in the same way that people that have excess weight do, and they travel down an alternate pathway. It's called the AgRP or the agouti-related peptide pathway, and that pathway tells us to eat more and store more.

Now when we talk about the brain, we have to recognize that the brain is interacting with our environment. So some people are very sensitive to the environment. So one person might walk down the street, pass a pizza place, and they feel like just walking past that pizza place, they gained five pounds, right? That's a bit of an exaggeration and not actually the case, but what they are honing in on is that their body is more sensitive to the environment in which they exist than maybe another individual, someone that signals well down that POMC pathway. And so that's part of the complexity of this disease that we call obesity.

Unger: Now it's interesting, I want to talk about this concept of the set point, which I pay a lot of attention on this and I always think about the set point as being something about your body that it does. But in your words, it's really about the brain telling us how much fat to store. Can people develop a new set point if they gain or lose weight, and like all those millions of people who gained weight during COVID, did they develop a new set point?

Dr. Stanford: You know, absolutely. The set point can be changed. And I actually want to look at it—I know set point sounds better, but it's more of a set range. And so let's think about ourselves. Just think about yourself, whoever you are, and you might notice that you tend to stay within a five to ten pound range of what your baseline is.

Now there are times when you might go up. Maybe during the holiday season, you're like, ooh, I'm a little bit outside of that range. And your body kind of recalibrates and you get back into that zone of what the body sees as comfortable. Even if you carry excess weight, let's say that your baseline is 250 pounds and you get up to about 260, and your body is like nope, I'm pushing it down back to 250. So you may not have had to do anything really significant except to shift back into whatever your norm is. And so this is the idea of set point.

Now notice, I didn't say anything about what the person did. A lot of the body's recalibrating them back to a certain weight, and so when we talk about people that have really a lot of excess weight, let's say those patients that come into me that weigh 500 pounds—most of us, no matter how hard we tried couldn't push ourselves up to 500 pounds. Our body would do something. And maybe we'd get to 300, but not 500. For most of us, our bodies will push us back into a range like, yeah, you may have gained 100 pounds, I can't make you gain 300 pounds. It's just a certain—it's like the body is tightly defining itself to where it wants to be.

So what happens often, particularly with lifestyle interventions, let's say you go on a diet, which I'm not a fan of going on a diet, but let's just say you do that. You notice you lose weight, you're feeling really great, but then as you get down to this lower what you feel is a different set point, your body is resisting it. And you start noticing weight gain. And you're like, well, wait a minute, but I'm doing all the right things.

What happens is your resting metabolic rate drops dramatically. And when it drops dramatically, the body can't defend itself down there. The brain is like, this isn't where we're supposed to be anyway. And so your body typically creeps back up to where it was before, much to your dismay, not because you did something wrong, but because it deviated from where the brain felt it should be. And so that's the concept of set point or as we're redefining it, set range.

Unger: So just hearing you, it just brings all the challenges that we hear about in terms of weight loss. So I guess the question is, how do we treat obesity? I know a lot of the news these past few weeks and months is focused on how some physicians are approaching that with pharmaceuticals. Let's talk a little bit about what are these drugs, and what do they do in the brain to help patients who have obesity?

Dr. Stanford: So different ways to treat obesity—I know the media has kind of made it seem like it's one-sided or one thing, but there are different things that different people need. We have to recognize that we're heterogeneous. None of us are exactly alike. The two of us sitting here, there may be some things that are similar, we're both human. But there may be other things that are very, very different that make our bodies respond differently to different things.

So we have this bucket lifestyle modification, things that we can do from a lifestyle perspective. And then let's go over to this bucket of medications or anti-obesity medications. And all of the medications that are available for use, either short-term or long-term, approved by the FDA, actually are often working on the brain.

The drug class that we hear a lot about is called the GLP-1s, or the glucagon-like peptide 1 receptor agonists. Say that five times fast. And they actually do exactly what we talked about a little bit earlier. Let's talk about the brain and why they are so, on average, effective for many people. Notice I didn't say everybody, and for many means that's not everyone, but for many people, they're effective because they do two key things in the brain. They upregulate that pathway, that POMC pathway that tells us to eat less and store less, and it downregulates that pathway of the brain that tells us to eat more and store more.

So when people take these medications, they'll notice, wait a minute. This doesn't feel like I'm having to work because we've changed how the brain sees weight. And that's how that mechanism works.

Now, there are other drugs that are out there that are outside of that class like phentermine, which has been around since 1959. That drug inhibits something called norepinephrine reuptake within the brain. Or topiramate, which stimulates something called GABA, or gamma-aminobutyric acid in the brain. So notice, we keep getting back to the brain. All of these things are working on different parts of the brain to change how the brain sees weight.

Unger: Now, let's talk a little bit more because I think what's been in the press a lot lately are people that are getting access to drugs like this to lose weight, fit in a dress, whatever you want to say, kind of celebrity-type drugs. The bottom line is they're expensive, and a lot of them are not covered by insurance, and they can become very hard to come by now because so many people are using them, let's just say, for weight loss. How do we make sure that the people who really need drugs like this can get them?

Dr. Stanford: This is a really complicated question, and the reason why it's so complicated is because we do have this issue with access and insurance coverage and the proper prescribing of these medications, right? These are medications that are used to treat two primary conditions, obesity and persons that have a history of type 2 diabetes. There is also some indication for people that have type 1 diabetes, although not as well defined.

So if we know that these are the patient populations that we're targeting, then obviously, there should be preferential use of these medications within those cohorts. We have to recognize that for obesity, these medications aren't often well covered by insurers, whether that's private insurers, public insurers. However, when patients do have type 2 diabetes, they often are covered.

There's the disparity between which disease process is more important, although I will acknowledge that when we're looking at type 2 diabetes, we know that 80% of patients with type 2 diabetes also have obesity. So we have to recognize that there's much of an overlap in these disease processes. 

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For the Hollywood community and the group that's going to just get on these just to look cute in a dress or look great for a reunion or a wedding, I would really push back on those individuals. There's been a major shortage of these medications for both type 2 diabetes and obesity that's persisted throughout 2022, for example. And as we go into 2023, we're seeing slight improvement in access, but I can tell you that from day-to-day, one of my biggest pain points with my patients is my patients not being able to get the medication that they need, they deserve, and that is used to treat their disease.

So I think equity is important. So we need to make sure that the people that need and deserve these medications, the people that actually have indication for the use of these medications are getting them. But that is going to take a bigger community. It's going to take insurers, private insurers, public insurers really making sure that the people that deserve and need access actually get them and not just the people that have the wherewithal, the means by which to acquire these medications.

Unger: Dr. Stanford, obviously drugs are not the only option, especially if a person can't afford a prescription or if it interferes with other medications or they just don't want to take a pharmaceutical approach. You've outlined a lot of the challenges here that are reality. What are the non-pharmaceutical forms of treatment that you recommend?

Dr. Stanford: Absolutely. This is a really great question, and I think it's important for us to recognize that medications, pharmacotherapy for obesity are not the only treatment option. We do start with obviously looking at lifestyle considerations. I mean, this is always our first go-to, looking at things like diet quality, where we have lean protein, whole grains, fruits and vegetables, and optimizing that to fit the individual person, recognizing that different people require different macronutrients than others.

Looking at physical activity, one of my favorite pastimes, and recognizing that we need at least 150 minutes of moderate intensity physical activity per week. But for some of us, we may get even more than that. We may see, for me, I'm a big high-intensity interval training person. But think about finding the right workout for the individual. A lot of times, particularly as physicians, we impose on individuals what we think they should do, as opposed to listening to them about what things they enjoy doing so that they can do them long-term.

It's important to recognize that sleep quality and duration plays a large role. A lot of people have disordered or disregulated sleep or changes in their circadian rhythm. And by that, maybe they're night shift workers, and they notice that as a night shift worker, they have gained weight. And so sometimes it's shifting into a normal pattern, being awake when it's bright outside, and asleep when it's dark outside that we see weight shifts.

Medications that we as doctors and other health care providers prescribe can lead to major weight shifts. Medications like lithium, Depakote, Tegretol, Celexa, Cymbalta, Effexor, Paxil, Prozac, Ambien, trazodone, Lunesta, gabapentin, glyburide, glipizide, glimepiride, long-term insulin, long-term prednisone, just to name a few medications that can lead to weight disregulation. Many of those medications acting on the brain, remembering that the brain is the primary regulator in where our bodies see weight. So those are important.

It's also important not to discount the role of metabolic and bariatric surgery for those with very severe obesity. We find that that implementation and/or intervention has the highest impact on changing weight status for individuals across the age and life course that struggle with severe obesity and obesity-related disease. And so there's different strategies.

Now, for many of my patients Todd, I will tell you that they have a combination of all of the things we just mentioned. Maybe they had surgery, maybe they are on medications, maybe they have lifestyle interventions, and maybe they may have been resistant to considering any of those things at the outset, and then over time, they recognize their body's resistance to change with any one intervention.

Unger: And that's quite a list of different interactions that you laid out in that list of drugs. You've obviously had practice in saying that. Something we talked about earlier, too, you mentioned the overlap between obesity and diabetes, in that case. Let's talk a little bit about what we're facing here. I mean, there's obviously a public health problem with both hypertension and pre-diabetes that's now exceeding 90 million people in the U.S.

And that's why, at the AMA, we've been working with clinical teams and health systems to address these two conditions. What are your thoughts on how physicians can help their patients with these conditions and obesity, and if obesity is a brain disease, how do lifestyle-change programs fit into that comprehensive total treatment plan?

Dr. Stanford: This is a great question, and I think one of the key things I want to point out, Todd, is the overlay between all of these conditions. We have over 110 million adults with obesity in this country as of today. You talked about 90 million with pre-diabetes, hypertension, et cetera. But what we do know is that there's a lot of overlay and a lot of interaction between each of these individual entities, these different disease processes.

And so we have to recognize that, first of all, we have two different camps of individuals—those that were trying to prevent developing more significant disease, and then those that already have these diseases that now intervention is key. And so we have to recognize that we want to prevent those that are in the pre-obesity range, the pre-diabetes range from developing more significant disease, but we can't discount the fact that we have these huge numbers of individuals that already have these conditions. And as physicians we have to be at the forefront of really setting the charge and treating these patients with dignity, respect, valuing them and where they are today, and making sure that they have the best and healthiest life going forward. So I think that's really key for us to recognize.

We can't assume that one thing that works for one person will work for everyone. We have to recognize, going back to that heterogeneity of who we are, different things, even within the same family, may work differently. And it's OK. It's just about finding the right treatment for the right person at the right time to get them to the healthiest person they can possibly be.

Unger: And we're just been talking really primarily about adults, but we know that obesity is not just an adult problem. In fact, again, lots in the news recently about this—it's affecting one in five children, and I'm sure a lot of parents out there have questions about how to help their children live a healthy life. What should pediatricians be telling parents about how to manage their children's weight, and also how to talk to their kids about it?

Dr. Stanford: As a pediatrician also, I'm going to put on my pediatrician hat, and I guess you guys can see the pediatrician hat now is on. I spend a lot of time talking with parents and families. And what I have found, particularly when you're dealing with pediatric patients with obesity, is to take this from a family approach. This is not just focused on the child and what they can do and what they've done wrong or what they could potentially do better. It's what can the family do better.

And when we focus on the family as a whole unit, I can tell you that we have much better outcomes, and the data supports this. So I think that's first and foremost. Can we work on those things that we talked about in the lifestyle realm? Absolutely. But the new pediatric guidelines do speak to the need to address and treat obesity more aggressively and sooner.

This is something that I've done in my practice for over 15 years, and I'm happy to see the AAP recognizing that if I have a 12-year-old come in, and he's four standard deviations above what's considered a healthy weight, that me telling him just to drink skim milk is likely not going to have a huge intervention or shift him into a healthier weight range. And so I think using the treatment modalities that are based on the evidence, and that's what we're using is the evidence to inform our treatments to recognize that for some, lifestyle measures will be enough, and that's great. But for those that need more aggressive therapies—medications, surgical intervention, a combination thereof—that we should be supportive and embrace the idea that we can treat these people early.

And why is that important? Because if you struggle with disease, whether it be obesity or hypertension or type 2 diabetes, as a child and start very early, you can imagine it's much worse as they cross the threshold over into adulthood. If you're getting these diseases at the age of 40 compared to the age of 12, what do you think your life expectancy is? What do you think the quality of life will be for those individuals? And these are really important conversations to have.

Todd, I recently had a 12-year-old that I've been taking care of for the last two years have a really important conversation with her parents, who I also take care of. And they said to her, well, what do you think about the work that you're doing with your weight doctor? And she was like, who are you talking about? And they were oh, your weight doctor. And she was like, I don't go to a weight doctor. And they were like, well, what about Dr. Stanford? She was like, oh, that's what she does? And I think that's really important because she had no idea…

Unger: Wow.

Dr. Stanford: …that she's been seeing … for two years, and that I am an obesity medicine physician. Why? Because while I do focus on weight and weight regulation, I do that at the very beginning of the visit, and then I just talk about her, her as part of that family unit. What can we do to make her life better? So much so that for two years that I've been treating her she had no idea that I was an obesity medicine physician.

And how do you do that? Well, it's by not hyper-focusing on the number on the scale, the number on the growth chart. Yes, it's there. We see it at the beginning of the visit, then let's focus on how to optimize her, him, they, them, theirs, whoever. I think this is really important. And I take significant pride in knowing that she had no idea what I do for a living and didn't feel like this was a combative visit, a visit that she has to be embarrassed of when she looks back at her 12-year-old self in 20, 30, 40 years.

Unger: That's a great segue into the next question I want to ask you because obviously, there's a lot of skill and experience that goes into the background of that story. And despite the prevalence of obesity, physicians aren't going to have that same understanding as you do, and they're not going to have that same ability to understand how to speak to a patient like that. And I think the estimates are pretty high percentage of doctors do have some bias toward individuals who are overweight or have obesity. So this is a real issue.

I want to talk a little bit more about that. And you also have got insurance companies that won't cover obesity drugs like they would medications for heart disease and hypertension, and that implies that they don't consider obesity a disease, either. So in the face of this, a lot of education that's needed. There's bias. There's a lot working against patients here. How do you see, coming out of your research and your work, physicians needing to have conversations like the one you just had?

Dr. Stanford: I think the key tenet—and this is something we learn, regardless of our religious background, et cetera, is to treat people how we want to be treated. So when you're going into that office visit as a physician, as another health care provider, what would you want if you were in the receiving end of that conversation said to you that would make you feel whole?

If you aren't doing that as a physician, then I want you to reconsider what you're doing. What would you want to be said to you at that moment? So that you can look back and be like, that was a really great interaction I had with that physician. That made me feel empowered, that I am not necessarily the problem, and that there's part of my biology that's working with this problem.

It's unfortunately something that we don't really learn in our medical training, but it's a simple tenet that you can use by just thinking about if you were on the receiving end, what would you want to hear? What would make you feel whole, valued, and somewhat feel like this is not the end of the road? And so that's really what I think about when I'm working with my patients. What would I want to be receiving?

And if I say anything or think about anything that doesn't quite fit that mold, then I need to change my thought process. And I can tell you that I didn't start there when I started my career. I would say, people are like, oh, I want to be happy and healthy, and I want to weigh this. And I'd be like, oh, well, I do P90X. I do Insanity. I do all of these things, and a focus on me, me, me and what I did, not recognizing that I also wasn't coming from a place of having struggle with obesity.

So I was doing these things that were maintaining me, but I wasn't coming from a place of having 100 pounds in excess or 200 pounds in excess, or whatever. I wasn't coming from that place. And so when I talked about what I did, so that my patients could say, oh well, I did this, I wasn't recognizing what their struggle was. I wasn't empathizing. I wasn't living in their shoes. And now, having taken care of thousands, tens of thousands of patients with obesity, I feel, I hear, and I try to live what it is that they live, and then think about what I can do better.

And each day, I work to improve. I don't know if that conversation that I had with that 12-year-old, such that she has no idea what I did, if you go back to me in residency, is that the same conversation that people that I took care of then thought? Because I didn't know about this disease. I was telling those kids, if you can just—I know you're working out for an hour a day, maybe an hour and 15 minutes, you know? Yes, and maybe, yes, you can just drink more water and these types of things, not recognizing that their degree of obesity was so severe that those interventions would likely not yield any measurable outcome for them.

Unger: Well, last question for you. You were recently appointed to the U.S. Dietary Guidelines Advisory Committee. How do you hope an appointment like this helps you further your work?

Dr. Stanford: Absolutely. Well, first of all, I'll acknowledge that of the 20 of us that are appointees, only three of us are physicians, and I think I may be one of the only two that are actually practicing medicine. And so I think this brings a different perspective to what the work is. There's one thing to do this in science, and there's one thing to actually care for patients.

And one of the things that I have seen as a person that's now in the middle of my 40s is that sometimes the dietary guidelines can be confusing for those with health literacy issues, with those from diverse backgrounds where some of the recommendations may not quite fit what their native culture is. These can feel a bit isolating. And so I'm hoping that my appointment brings that patient element. That element of looking at diverse populations across the age range.

This time I was nominated by the National Council on Aging, but previously, I have been nominated for this, was not selected by the American Academy of Pediatrics, they nominated me previously. So I think that speaks to being able to talk about the pediatric side, talk about the aging population, and then bring this work into particularly those that have struggled with this disease of obesity and who have been told to do these things that are doing these things that are still struggling with the disease, not assuming that they aren't doing the right things, but maybe we can do things to help them be their best self.

And so that's what I'm hoping my appointment brings to the committee as we do our work.

Unger: Are we going to see changes to the food pyramid?

Dr. Stanford: I don't know because there's 20 of us. I can't speak to what's going to happen. I will tell you that we have an upcoming meeting with just in the next week with the committee, and it'll be interesting because our first meeting as a group. We'll have two years to work on the 2025 guidelines, and it will be a lot of work. And I recognize that we come from different perspectives, different backgrounds. I mean, I'm hoping that we're able to coalesce these backgrounds and understandings of what we see and things that can improve to make the best possible recommendations to the U.S. people.

Unger: Just throughout this conversation, it just strikes me over and over again how much there is to learn about the situation that we face ourselves and the challenges that we didn't anticipate. It's just so important to do what you're recommending, which is to reframe the discussion and really think differently about this.

So thank you so much, Dr. Stanford, for joining us here today and for all the work that you're doing on this important topic. We're going to be back soon with another AMA Update. You can find all our videos and podcasts at Thanks for joining us today. Please take care.

Disclaimer: The viewpoints expressed in this video are those of the participants and/or do not necessarily reflect the views and policies of the AMA.