Obesity Medicine in the Age of GLP-1s

JOEL BERVELL: My guest on this episode of The Dose is Dr. Fatima Cody Stanford, an obesity medicine physician–scientist at Mass General Hospital and an associate professor of medicine and pediatrics at Harvard Medical School. Her work bridges the intersection of medicine, public health, policy, and disparities. We had a conversation on The Dose two years ago, and so much has happened in the obesity medicine space since. I wanted a chance to have another conversation to talk about what we’re learning as GLP-1 medications to treat obesity have become more widely available.

Dr. Stanford has served as the chair of the minority affairs section for the American Medical Association, chair of the American College of Physicians Obesity Advisory Committee, and is the director of diversity and inclusion for the Nutrition Obesity Research Center at Harvard. This year, Dr. Stanford was one of more than 50 international experts serving on the Lancet Commission on Clinical Obesity, proposing a new definition in diagnostic criteria for obesity.

Dr. Stanford, thank you so much for making time for this conversation. I’m so happy to have you back on The Dose.

FATIMA STANFORD: I’m happy to be here on The Dose.

JOEL BERVELL: When it comes to GLP-1 medications that became more available about two years ago now, you spent a lot of time here with me and across the media helping people understand why medicalizing obesity treatment was such a significant shift, both as a researcher and clinician. That was in part the reason I wanted to have you back to hear what you’ve learned since then and to let our listeners benefit from your perspective.

So I wanted to go back to that. As these medications have reached many more patients, do you view the benefits and risks differently today than you did two years ago?

FATIMA STANFORD: No. It’s interesting. I have thousands of patients that have benefited from these therapies across the age spectrum. We have individuals as young as 12 that can be on these therapies, and I have patients in their 90s on these therapies. So I really do have a framework of reference, being an internist and a pediatrician, of seeing how these medications work across this full spectrum.

What’s been very interesting, however, and particularly as we talk about that access issue, we have a broader landscape of who can access them. And then we hear about discontinuation rates and things of the sort. But as someone who exclusively treats individuals that have a history of obesity, I can tell you that when people are coming off of therapy, it’s not usually because they want to come off of therapy. It may be secondary to the fact that they lose coverage. Or for my older adult patients, they go on Medicare.

We know that Medicare, for example, does not cover these medications for patients with obesity. So I can tell you that there’s a lot of angst and anxiety for my older adults when they’re making that transition off of their employer-sponsored insurance that may cover them on to Medicare: “What are we going to do?” And if they don’t have the financial resources, which we know that these medications are exorbitantly priced . . . we know the price has come down since we last talked, the prices come down. But still that price point can be cost prohibitive for many individuals. So what happens?

We’ve also learned since I last talked to you about what are the benefits of these agents in terms of who is most likely to glean the most benefit from reducing major adverse coronary events, et cetera. And I would definitely say it’s those older adults. So the people that are most likely to glean benefit are having those medications pulled back.

So I’ll give one key example from a policy perspective. I’m based here in Massachusetts. Blue Cross Blue Shield of Massachusetts has decided to drop coverage for patients with obesity as of January 1st, 2026. That will affect at least a third of my patients. We treat 42,000 patients in our clinic here at the MGH Weight Center. That is a sizable number of individuals that will lose coverage for these medications.

So when we talk about, “Oh, discontinuation rates, people are coming off because of side effects.” I want us to take significant pause and think, do they really want to come off or did they lose coverage? And I would say that the latter is usually the case.

JOEL BERVELL: Talking about this idea of accessibility more broadly, has accessibility played out in unexpected or predictable ways from your perspective?

FATIMA STANFORD: Well, so I think that we’ve seen an improved access overall. So we’ve seen initially that insurers have decided, “Okay, we’re going to cover GLP-1s for the treatment of obesity.” But just as quickly we’re seeing this coverage being pulled back. And we’re seeing that happen with employer-sponsored insurance, we’re seeing this happen at the federal level. And it’s really concerning because if we look at the studies that have been published on what happens when we discontinue therapy for the treatment of obesity with Wilding and colleagues publishing on semaglutide, right? That’s the Ozempic, Wegovy. And Aronne and colleagues publishing on tirzepatide. We know that 85 [percent] to 90 percent of individuals will have significant weight regain. And not just the weight piece. Always want to talk about this, the reemergence of obesity-related chronic diseases associated with that weight regain.

And so one of the things that I think if we look at when these companies do decide, insurers decide to pull back on coverage because they’re like, “Okay, well the cost is exorbitant, i.e., pharma has decided to price these drugs at a price point that is unsustainable for us.” And I’m going to explain why I think this is. I’ll explain where I think pharma could make some adjustments. But if you look at it, they’re looking at the short-term benefit. Okay. So if I’m an individual and I’m on X plan, particularly they’re thinking about like, “Okay, I want return on investment very quickly. Two to three years, that’s all I’m thinking about, is how the Congressional Budget Office thinks about things also. I want two- to three-year investment because as an individual employee, maybe I’m going to leave and go to another job.”

And so I’m only going to get that benefit from that individual within a two- to three-year time span, unlike individuals that were baby boomers. For example, I’m Gen X, which is supposedly the forgotten generation, which I have issue with, which is another story for another day. They jump over to millennials, et cetera, et cetera. But unlike a lot of the baby boomers who stayed within a job for 20, 30, 40, 50 years, people are leaving jobs and they’ll flip, flip, flip, flip, flip. So they don’t get the benefit of seeing that person on a plan and what that does for their company. When they do that cost analysis, they’re looking for that quick return on investment just like the Congressional Budget Office.

Now you could say, “Okay, well let’s look at the extended benefit because these patients aren’t needing to get admitted to the hospital for chronic disease, et cetera, et cetera.” Now, we could also look to pharma and we could say, “Well, why is the price of the agent here in the United States so much more than it is in Canada or the U.K. where there’s single-payer systems that have been able to negotiate a much better cost for the drugs and so the price of the agent is much lower there?”

And so these are some significant issues that we have to think about of what type of market that we’re in, where a single-payer system doesn’t exist, so the price point for the agent is going to be much higher. They’re able to make up and recoup costs from research and development and things of that sort. And we know that the U.S. market is willing to pay more.

JOEL BERVELL: Absolutely. That entirely makes sense. Bringing it down back to a little bit of an individual level, I want to talk about patients and how they’re feeling right now. Can you share any anecdotal insights or new data on how patients are feeling with GLP-1s? That could be behavior in compliance, shifts you’ve observed, mental health effects, food noise?

FATIMA STANFORD: Absolutely. I would say overall when patients are on the medication, if, and I’m going to say that again, if they’re responders, they feel really great. Those patients that aren’t responders don’t feel this way. So I’m speaking for those patients that are responders. They are getting significant benefit in terms of being able to just navigate everyday life, where they’re not consumed with having to be thinking about what is the next meal. And then not only what is the next meal today, what is the next meal for the rest of the week. Because often this idea of food noise, which really isn’t something that we would say in the medical setting but was really coined from the GLP-1 era on social media and the kind of mainstream media, the food noise or volume of concentration on food has been blunted, either turned down, or is on mute if we kind of want to think about it that way.

And so patients feel like anxiety, stress has been reduced because they’re no longer having to navigate that if they’re doing well on these pharmacotherapy agents. So patients are able to engage in family life, in their work life, be more productive in all of the things that they’re navigating.

When patients are experiencing potential side effects, it’s usually when they’re titrating up on meds. So it’s usually in that titration that patients would experience side effects. But once they get to a steady state, they kind of feel like they’re able to just kind of cruise through life. Patients, of course will . . . depending upon who they are, these medications may be an adjunct or even add-on to metabolic and bariatric surgery, for example. So it just depends on what the severity of what’s going on. So patients, if they’re doing well and if they’re responding, you can imagine they want to retain coverage of the medication.

I would say that one of the stressors associated with these medications is the prior authorization piece of the puzzle. So, for patients that don’t have an infrastructure within their physician’s office where prior authorization can be carried out, they may not necessarily lose coverage, but if their prior authorization expires, they may go off of therapy and then need to be titrated back up on their therapy. So that can be a source of significant stress and angst and coming off the medicine, having to restart the medicine and then titrate back up. So prior authorization can be a bit of a nightmare because these medications do require preauthorization unless someone’s a self-pay patient and then of course doesn’t need that prior authorization.

JOEL BERVELL: And then I’m curious about how you’d characterize shifts that you see in culture and attitudes around these drugs right now. I think about Serena Williams, who recently came out and said that she was using GLP-1’s. And then what do you see when it comes to your colleagues if they’re shifting towards a more medicalized approach to obesity?

FATIMA STANFORD: Yeah. It’s interesting. With Serena, I think that maybe some of the backlash that she may have faced is because people see her as just an athlete and they presume that as an athlete, it’s more of the calories in, calories out mantra. She should just be out there playing tennis. She’s by far, I would say, the most recognizable figure in tennis of our time. I think there’s no one that does not recognize her as probably of the GOAT. But we also know that Serena struggled with things like pulmonary emboli and other things, so we don’t really know all of her medical history. But going back to whether or not I see more of my colleagues being willing to consider the use of these therapies, the answer is indeed yes. Now, I see my colleagues that are more likely to shift in this direction are the ones that are themselves using these therapies.

JOEL BERVELL: Interesting.

FATIMA STANFORD: I do treat quite a few physicians. And it’s interesting when they themselves are willing to share their journey with their patients and they are on the receiving end, then they start to realize, “Wait a minute. Maybe there is some medical piece to this puzzle. Maybe I need to be giving the same level of care to my patient population,” particularly if you’re in the primary care arena or as a specialist, particularly in cardiology, endocrinology, gastroenterology. These are individuals that are very likely to consider these therapies. And so I’ve definitely seen a shift.

JOEL BERVELL: I think that’s so insightful because just even since starting residency, I’ve definitely noticed the comfort level of prescribing things has to deal with your proximity to it, right? And so it’s kind of this cycle of individuals becoming more comfortable with the medication that could potentially help a lot of people.

In the introduction, I mentioned the Lancet Commission on Clinical Obesity, where you and more than 50 international experts proposed a new definition in diagnostic criteria for obesity, with a renewed focus on adiposity, or excess fatty tissue in the body. Can you walk us through what that proposal entails and why redefining obesity in this way matters?

FATIMA STANFORD: Absolutely. Let’s look at what the traditional definition of obesity looks like and let’s look at what we are proposing. So the traditional definition really wants to shape everyone by looking at this idea of body mass index. We just take height and weight and we decide that you have obesity. Can we just give you a number and say your BMI is 31 and now you have a health problem and assume that everyone that has a BMI of 23 is healthy? Medicine has really decided, “Hey, this is really simple.” But simple and easy doesn’t equal right, okay?

And so when a person goes into their doctor and you get this number and this number is supposed to tell you whether you’re healthy or not, the Lancet Commission challenged this notion and says, “Okay, well, is this correct?” And the answer to that is indeed incorrect. We need to look at adipose or fat mass and determine where that may be located in the body, particularly is it around the organs, what we call visceral adiposity, and determine if it’s located specifically around organs versus sub-Q or subcutaneous adiposity and whether that increases your health risk.

So the Lancet Commission looked at this information and decided that we may need some additional values like doing something like as simple as a waist circumference, which would not be challenging in either low-, middle-, or high-income countries. We don’t need to necessarily run you through a DEXA machine, which of course would be cost prohibitive in low-resourced environments.

And if you’re carrying extra weight around your midsection and have obesity-related diseases with certain BMI issues — and we actually eliminated BMI, believe it or not, until we get to that severe category — then we really need to start paying significant attention. But let’s go down to these lower BMI categories. We could have a person with a BMI of 32 who doesn’t carry excess adiposity that has led to any disease process. And so do we need to define that person in the same way as someone that does have a BMI of 32 that does carry health risk? And so we need to really individualize how we look at individuals. And that’s what we were seeking to discern or capture with the Lancet Commission. Let’s not assume that all lean people are healthy and that all persons that may have a larger body type are unhealthy.

JOEL BERVELL: Absolutely. And what was that like when it comes to the negotiations around that proposal? I’m sure everyone may not have agreed upon wanting to change these definitions.

FATIMA STANFORD: Well, I can tell you that it took us quite some time, over two years, to really come to consensus. But when we did the work, the deep work, in terms of every single measure, that we came to over 90 percent consensus amongst the 58 commissioners. And I can tell you that it took some tough work.

And I can tell you that even now, even with over 75 organizations supporting the Lancet Commission criteria, there’s still going to be pushback. I will debate this on the floor at the Obesity Society against people that are very committed to wanting to retain BMI as our measure because it’s, like I said, easy. But I said easy doesn’t equal good. I need to evaluate each patient for who they are. I can’t assume that all patients are the same. We are two individuals of African descent. We’re not the same. And I need to make sure that patients get the proper evaluation. And I just don’t, because it’s easy to just give them a number and send them out the door, assume that they have the proper diagnosis.

And so I’m willing to do that deep dive. I’m willing to evaluate each person on the individual basis that they should be evaluated and making sure they get the tailored treatment regimen that they need to get the health interventions that they need.

JOEL BERVELL: And looking ahead, what do you see as the near-term and long-term impacts that this new framework could have, both in the clinic but also in broader public health policy?

FATIMA STANFORD: I really do think it’s going to challenge everything that we’ve learned up until this point. I mean, forever we have said, “Oh, well, let’s just look at the person’s BMI,” right? But I think it’s going to, for lack of better way of saying it, muck up the system, right? It’s going to challenge the notions that everyone should be evaluated.

We’ve been practicing what I consider to be street corner medicine, which is we look at someone and say, “Oh, they’re a larger person. They must be unhealthy.” Oh, they’re a leaner person, they must be healthy.” But what if that lean person became that way because they were using a substance? Let’s say that substance was something like meth. Believe it or not, the FDA approved methamphetamine for the treatment of obesity for over 45 years. I mean, so maybe they were using that to become lean. But is that a healthy way to achieve leanness? And what if that person that happens to be a larger body type, what if they’re doing ultra marathons on the weekend? And you haven’t done a deep enough dive. You assume that they’re unhealthy just because of the judgment that comes with the bias and stigma that we associate with those that are larger body types.

So instead of making the judgment, do the deeper dive, do the clinical investigation and see what is going on with each individual before we make that assumption.

JOEL BERVELL: That’s so important, doing the deeper dive, not relying on our stigmas and our biases that we often bring into the clinic room.

FATIMA STANFORD: Right.

JOEL BERVELL: Two years ago we discussed genome-wide studies that indicate a higher predilection towards adiposity, genomic evidence that some groups have a tendency to store more fat. Is this information having any more impact on treatments today?

FATIMA STANFORD: No, unfortunately. I don’t think that people are paying very close attention to those groups that have a higher degree of adiposity. For example, I’m going to look at, let’s say, some of our Asian colleagues. For example, they come in with much lower BMI. So we’re going to go back to this idea of BMI. And they will carry significant high levels of visceral adiposity at lower BMI levels.

So let’s just throw out a BMI for example. Their BMI may be 26 or 27. But if you look at their visceral adiposity, even by kind of more advanced-level measurements, for example, let’s say we have a DEXA scan on them or even MRI-level data that shows how much visceral adiposity they’re carrying. And they will have also obesity-related disease. Maybe they have type 2 diabetes or mast cell, which is fatty liver. Another word for fatty liver or metabolic-associated steatotic liver disease. And they’ll have all of these things, but if you look at them visually — the street corner of medicine again — you assume, “Oh, well, they must be very healthy.” But you get their chart and you’re like, “My gosh.” And then you listen to their family history and you listen to all of these chronic diseases at a much lower body mass index level, hence the problem with the utility of BMI across certain groups.

Now, if you look at where we are supposed to be able to use these medications, you’re not necessarily supposed to use them unless the patient has type 2 diabetes or certain BMI cutoffs. But if we tailor it to that individual that already has these obesity-related diseases along with this significant high level of adiposity, then you would be able to use, let’s say, a GLP-1 therapy on this individual and get some great outcomes.

Now, some of the studies that have been published in JAMA, New England Journal [of Medicine], if you look at those studies for those that are of Asian descent — China has done several of these studies — you’ll notice that they do lower BMI cutoffs because they recognize in these populations that they need to do lower BMI cutoffs to really capture this excess adiposity in those populations. But I find that we do get pushback. And I would often have to do kind of a back to back with insurers to get coverage for pharmacotherapy because like I said, they’re hyper-focused on BMI, which is what the criteria indicates in the label insert for these medications. So that’s why I’m hoping that if we shift into the Lancet way of thinking, I’m not going to just use this BMI cutoff and I’m going to use the person in front of me that’s demonstrating high level of disease despite what the BMI number is showing me.

JOEL BERVELL: And so it sounds like the reason why this isn’t taking more into account is because BMI is still used as a proxy, and so there’s that fallback towards it?

FATIMA STANFORD: Yes. Absolutely.

JOEL BERVELL: Okay. I’m curious . . .

FATIMA STANFORD: It’s easy.

JOEL BERVELL: Yes.

FATIMA STANFORD: It’s easy, right?

JOEL BERVELL: It’s easy to fall back into the status quo of what we’ve done all the time. Kind of related to that, is body roundness index taken into account here? How has that been playing into the conversations?

FATIMA STANFORD: Yeah, let’s look at the BRI. So people may be like, “What is he talking about? The BRI?” So the BRI really came out in around 2010, 2011. It comes out of a little bit of the math world. Dr. Diana Thomas, who’s at West Point, came up with this body roundness index. It looks a bit more thoughtful in looking at adiposity, where adiposity exists, particularly if we think about the midsection and things of that sort.

I would say that the utilization of the BRI is less in consideration because it hasn’t been taken into electronic medical records. Anytime something gets uptake in Epic or one of the big medical record systems, I do think that there’s some clinical utility in BRI that definitely is better than BMI. And so I think that that would be a better tool if someone’s like, “Okay, we have to use just a number” that that would be a better tool. But I think using something like waist to hip ratio, waist circumference and things of that sort also allows us to get that data without shifting just to BRI.

JOEL BERVELL: Absolutely. And right now, there’s a highly profitable race to refine and improve these drugs, these GLP-1s. What do you see on the horizon? And is it mostly marketing or is it real next generation that we have to be looking forward?

FATIMA STANFORD: No, there’s real great drugs that are coming forward. Let’s look at some of the things that people are very excited about. For example, there is a triple agonist medication, which right now, if you think about what we have currently available, is a dual agonist. So a triple agonist means we’re going to add another agent, so that would be glucagon into that. And so with that, we would anticipate higher levels of weight response.

There are other agents that are also on the horizon, so we have GLP-1 receptor agonists. There’s antagonists. So you’re like, “Well, it antagonizes. Will that help us lose weight?” Believe it or not, there are some on the horizon with once-monthly medications. There’s also other combinations with amylin, which is a different category of medications. And so when you look at this race, they’re looking at different pathways, different combinations.

And why I’m excited about it is that I want to have as many tools in the toolkit for my patient population that may respond to their biology, recognizing we’re heterogeneous. And so it’s exciting. What is less exciting for me is: Will these be covered? I don’t want these to just be shiny objects on a shelf. I have shelves behind me that I can’t reach, right? It’s only useful for me if I can pull that object off the shelf and give it to my patient. And if it’s an effective tool, be able to sustain use for my patients.

JOEL BERVELL: And the data’s telling us right now that 75 percent of Americans have overweight or obesity. If these drugs become more widely prescribed, do you think we’re likely to see those prices then come down?

FATIMA STANFORD: Absolutely. I mean, I think so. Even if we have looked at what’s happened in the last two years. When we last talked, the price point for these medications was somewhere between $1,000 to $1,600. The price point for the meds now, the highest price is $500. I mean, that’s a significant difference. So I anticipate that as more agents become available, as we get orals on the market, that these price points will continue to come down. As we introduce more competition into the market, then you’ll definitively see the price come down.

JOEL BERVELL: And we talked about those profits, but let’s also discuss pricing and the psychology of fair pricing when it comes to obesity drugs. Are efforts to make GLP-1s affordable affected by biases against people that have larger body habits or people of color? There’s a study that was published in 2024 that documented racial disparities in prescribing. So I’m curious how you might see this link to cost, if at all, today in looking ahead.

FATIMA STANFORD: I don’t think it’s so much an issue with regards to like, “I’m not going to price this fairly because of the populations that are affected.” I mean, if we look at obesity, this affects all groups regardless of your political leaning, regardless of your racial/ethnic background. We can say that there is a higher predisposition for individuals that are of certain racial/ethnic backgrounds, certain genders, Black women we know have the highest rates, particularly here in the U.S., which is why I went into this field. But there isn’t one group that isn’t affected, right? We can’t be like, “Oh, those individuals don’t ever develop obesity.” We know that this affects everyone. So I wouldn’t say that that is much of an issue.

But like I said, I think one of the things that I’m really excited about, particularly as we see the potential for an oral medication becoming available relatively soon, is that if we have medications that are between 350 and 500 [dollars], the out-of-pocket costs for the medicines that was driven down, that if that’s the price point coming directly from the pharmaceutical companies, that if they have an oral, that they’re going to have to price that below that. And so this will become more accessible to everyday Americans.

JOEL BERVELL: Absolutely. Well, Dr. Stanford, I want to say thank you so much for once again sharing your expertise and perspective with us today. It’s always a privilege having you to learn. I get to ask my personal questions I’ve always been wondering about that I see in the clinic. And I know our listeners are going to take so much away from this conversation.

FATIMA STANFORD: Well, thanks so much for having me. I’m glad to be able to share.

JOEL BERVELL: This episode of The Dose was produced by Jody Becker, Mickey Kapper, and Naomi Leibowitz. Special thanks to Barry Scholl for editing, Jen Wilson and Rose Wong for art and design, and Paul Frame for web support. Our theme music is “Arizona Moon” by Blue Dot Sessions. If you want to check us out online, visit thedose.show. There, you’ll be able to learn more about today’s episode and explore other resources. That’s it for The Dose. I’m Joel Bervell, and thank you for listening.