Atheendar Venkataramani: Opportunity, Hope, and Health

Harlan Krumholz: Welcome to Health & Veritas, I’m Harlan Krumholz.

Howard Forman: And I’m Howie Forman. We’re physicians and professors at Yale University. We’re trying to get closer to the truth about health and healthcare. We’re excited to welcome Dr. Atheendar Venkataramani today. But first, we like to check in on current hot topics in health. And Harlan, you just came back from a major conference. Can you give us a little inkling of what you learned?

Harlan Krumholz: Yeah, I was at the American College of Cardiology Conference. They have Scientific Sessions once a year—it was in Atlanta this year. Howie, these big meetings are back. I don’t know what it looks like in radiology, but for the first time, the halls were packed, each of the sessions were very full, there was a high energy. I had this feeling, you see this remote work, everything’s remote, I wondered whether the big cardiology meetings would really rebound. And the ones that had been just after the pandemic have not quite been what they were before. This one was even more than where we were in 2018, I believe. I don’t know what the final numbers were, maybe they had 20,000 people. But it was more than the number of people, it was a sense of engagement, excitement, also the diversity of individuals, the various different career stages. I was really impressed and felt again, like I had maybe many years ago, that these were worth attending because of the kind of personal energy.

Howard Forman: Quick question! What do we do when every cardiologist is in one city? What do we do for those of us that don’t have a cardiologist?

Harlan Krumholz: Well, you know that the studies have shown that actually heart health improves when all the cardiologists are sucked into a single location. Somebody published that a while ago. No one’s ever figured out why that is, but—

Howard Forman: Ha ha!

Harlan Krumholz: …question about what we’re doing. Hey, I wanted to talk to you about two studies that came out.

Howard Forman: Yeah.

Harlan Krumholz: And there’s sort of a theme about this. In medical school, we’re taught in a very linear fashion, we need to learn about underlying physiology and then pathophysiology. And that the world should progress in very logical ways as we understand how the body works; it should deliver us to really understanding what drugs to use and how we should treat patients. But we know in real life it doesn’t actually happen that way. Of course, you and I havetalkedadnauseam about the GLP-1 receptor agonists, these anti-obesity medications.

Howard Forman: Not ad nauseum—you can’t talk about it enough.

Harlan Krumholz: I know. Well, I sort of feel that way. Well, let me just talk about a study that appeared, led by our former student, Mikhail Kosiborod, who was here for residency and also did the Clinical Scholars Program with me, and—you know very well—who’s now a cardiologist in Kansas City. He led a study that looked at semaglutide—that’s this Ozempic and Wegovy medication—in patients with obesity-related heart failure and type 2 diabetes. Now, we’ve been having a lot of trouble really treating heart failure with what we call preserved ejection fraction. The heart’s squeezing normally, but people are manifesting heart failure. It’s not that the heart—that we can see—has been damaged in its squeezing function, but maybe it’s stiff and the pressures go up and the lungs still get full or edema, and people suffer from this. And we haven’t really found very good ways of doing it. And obesity is associated with this condition; many people who have this condition have obesity.

And it was Mikhail’s idea, with several others, to try these medications to see whether or not they would make a difference. And he studied this in people without diabetes to great effect. And now he’s studying it in people with diabetes. And it’s remarkable—this drug leads to large reductions in heart failure–related symptoms and physical limitations. And people do really well; he’s going to have further work. I think that’s going to allude to the fact that this isn’t just about people feeling better because they weigh less, they’re better able to move around, but this is really about changing the nature of the cardiac function and the heart—

Howard Forman: And I think, if I’m not mistaken, most of these studies show that these findings start to present before the major weight loss.

Harlan Krumholz: You’re a good student of the literature, Howie.

Howard Forman: I’m trying.

Harlan Krumholz: That’s an astute observation, that people start doing better even before the weight loss has occurred. But then I’m going to tie this to the other one, I’m going to try and get done with this quick because I know we’ve got a big interview coming up. The thing is, and as you know, there’s a study just came out this week that said, these drugs are good for Parkinson’s, perhaps, right?

Howard Forman: Yes.

Harlan Krumholz: So the weird thing is, nobody still knows, how do these drugs work? Even when in the beginning they were saying, “Well, the emptying of the stomach” or “the this” or “the that.” But now they’re thinking, these are really brain drugs, they’re changing the wiring in the brain, which is having an effect on how the body works. These could unlock a whole new understanding. But right now, millions of people are on these drugs, and not one person can tell you exactly how they work. But we only know that empirically, they’re providing massive benefit, and I think that’s fascinating. And I wanted to just link that to one other study. So that study was published in The New England Journal of Medicine.

There was another study on coronary sinus reducer for the treatment of refractory angina. So that sounds kind of big and fancy, but in essence, there’s a device that’s used in the heart. I don’t have to get any deeper than that just to say that they thought it would improve heart’s blood flow by using this sort of a reducer in the coronary sinus, a certain part of the heart. But the central premise is there’s a device you put into the heart, and it will improve myocardial blood flow, heart blood flow. And that improved blood flow will address the pain that people feel from inadequate blood flow called angina, called the heart pain.

Howard Forman: Right.

Harlan Krumholz: So they do this trial, it’s a cool trial led by a colleague of mine, Rasha Al-Lamee at Imperial in London, and a whole range of other folks. And these are hard studies to do, so they basically... It’s a relatively small study, but they’re looking at this. And in the end, no increase in myocardial blood flow with the device but an important reduction in angina.

Howard Forman: Wow.

Harlan Krumholz: So they had this whole thing worked out. You use this device, it improves blood flow, and that’s going to help improve symptoms. That intermediate step of how they thought it worked, didn’t work—

Howard Forman: Is not how it works. Yeah.

Harlan Krumholz: ... but actually, people improved, and it was a suggestion that this is a real effect. So now people have to figure out, “Well, how did it work? And why did it work?” So I’m just saying, it’s interesting in medicine, we think we’re so smart, we try to develop all these new things, but sometimes it’s really about deeply observing things. And it’s the empiric observations that have to take us backwards to try to figure out, how in the heck did that work? And what new insights can that unlock? Rather than being so smart that we understand exactly how the body works and then being able to move just literally forward. Anyway, I just thought this was interesting. The meeting was great, lots of good articles and stuff, but yeah.

Howard Forman: Yeah, it goes back to a point I make a lot, which is you got to be really humble to be in medicine, because things change an awful lot, and we don’t know everything at all.

Harlan Krumholz: Yeah, so that humility is important, and in keen observership, observing, for example, the GLP-1 receptor agonists were built as diabetes drugs, but people noticed that people lost weight. That was almost a side effect and then built on that from there. All right, let’s go to our guest. Thought that was interesting, I enjoyed the meeting, and lots of interesting stuff came up. But yeah, let’s go on.

Howard Forman: Dr. Atheendar Venkataramani is an associate professor of medical ethics and health policy at the University of Pennsylvania’s Perelman School of Medicine. In addition to being a practicing physician within the Penn Health System, he’s also the director of the Penn Opportunity for Health Lab. Which works to understand the interplay between the American Dream and America’s health with a focus on policy. Additionally, he’s a faculty research fellow at the National Bureau of Economic Research. And broadly, his research focuses on the determinants of health and what we might do to improve the health endowment of those who are all too often left behind. He has been widely published in journals including The New England Journal of Medicine. He holds a bachelor’s degree in biology and economics from Duke as well as a master’s and PhD in health policy with a concentration in economics from Yale University. Which is when I was fortunate to first meet him and was fortunate to have him work as a teaching fellow. He holds an MD from Washington University in St. Louis as well.

And first, I just want to welcome you to the podcast, it’s great to have you here. I am so impressed with the work that you’ve been able to do. And to point out for our listeners that it is rare to find true clinical health economists, people who practice medicine and are true PhD-level health economists, and you are at the top of that list. I wanted you to take a minute to explain to our listeners a little about the Opportunity for Health Lab. What does it mean? What does it intend to do? And what type of early work have you reported from that?

Atheendar Venkataramani: Yeah, sure thing. Howie and Harlan, thank you so much for having me on this podcast. Before we started recording, I didn’t get a chance to tell you that I’m a big fan. So it’s really cool to actually be able to be a guest. And yes, I’m really excited to talk about the Opportunity for Health Lab. This is a group that we started now three or four years ago. And the folks that are kind of helping me run it are Rourke O’Brien, who’s a sociologist at Yale, and Alex Tsai, who’s a psychiatrist and health services researcher at Mass General Hospital. And the basic premise of our lab is that across America, there are people that for whatever reason are unable to dream big and meet their aspirations and expectations about the future. They feel stuck in place for a variety of reasons. And the American Dream, at least as we had imagined it, seems distant to them, if not achievable at all.

And so we were interested in how do those types of factors, the lack of being able to access the American Dream, the lack of being able to achieve upward mobility, feeling stuck in place when it comes to jobs, finances, relationships, being stuck without a political voice, how does that factor into our health and wellbeing? And this idea actually came out of a patient encounter that I had when I was in Charlestown, Massachusetts. I was a primary care doctor there, and I had a patient tell me that he didn’t see the point of quitting smoking because, “I’m never going to exit the station of life, I’m stuck where I am.”

And he was in a working-class part of that town and was having a lot of difficulty finding meaningful work and financial security. And so over the years we’ve taken that insight that came from the clinic and tried to look at, I think, really this bigger problem of why is health in America so challenging to achieve for many, many people. An increasingly larger number of people are experiencing stagnation in terms of their mortality rates or even increases in mortality. Life expectancy as a whole has been falling. And compared to our peer countries since the 1980s, we have fallen off the curve in terms of secular improvements in health.

And so, we started looking. Okay, so, places where upward mobility is hard in terms of one’s income. We see that those are the types of places where health is poorest and where health has declined the most. Policies that tend to shape people’s ability to gain upward mobility, whether it’s social policies, like affirmative action or immigration reform, or criminal justice policies. These types of policies tend to have effects on people’s expectations about where they can go in the future. And we accordingly see their health behaviors follow, for better or for worse. Places where there’s been industrial decline, plant closures, automation replacing jobs—these are places where we’ve seen health suffer as well.

And we tried to lay that groundwork first to show that policies that boost opportunity can boost health, and policies that constrain opportunities can harm health. And what we’ve moved on to since is trying to understand (a), how do we create a society that boosts opportunity for everybody? and (b), what are the buffers that we can put in place so that the disappearance of opportunity for a period of time doesn’t mean that people have to get sick and die from it?

Harlan Krumholz: So it’s terrific to see you get you on, first of all, another one of Howie’s former students who continues to do amazing things in the world, so that always impresses me. I wanted to just take up a couple of your pieces, and I want to start with one that you published in The New England Journal of Medicine. First of all, love the title: “Affirmative Action, Population Health, and the Importance of Opportunity and Hope.” It’s an art to get the right tenor on a title. And I just wanted to read one paragraph, two sentences, and just get your reaction to what led you to write this and how do you think about it? But you said, “Policy debates related to affirmative action have typically focused on its effects on education, employment, and earnings. These debates, however, have generally neglected the important role of affirmative action may play in shaping population health.”

So your intent in this piece was sort of to broaden our thinking about the potential benefits of these kind of programs beyond what it can do for an individual with regard to “education, employment, and earnings.” So what brought you to that? And maybe you can just share a little bit about what your central argument was in the piece.

Atheendar Venkataramani: Yeah, I think there’s a couple of things in that piece that I was trying to make clear to people. One is that social policy is really important for health policy. We often don’t think of it that way, but social policies do a number of things. They change people’s material circumstances; they provide people opportunities that they may have had or not had before. And they also can change people’s thinking by virtue of what the intent of the policy is. It signals something to people about their sense of belonging in society, potentially stigma that they may face and what their future may look like. Affirmative action was a policy that if you look at who was affected in terms of... this is for college admissions. If you look at who was actually affected in terms of college admissions, it’s a relatively small slice of American high school students who are on the margin of going between a certain college and a more selective college, who may have been moved by affirmative action in one way or the other.

But affirmative action as a whole is a really large issue that we talk about, and the idea that there is a policy that may provide people the opportunity to go to a place or gain an education or be in an environment that they wouldn’t have had before, that goes beyond the people that are narrowly affected in terms of the mechanics of who gets into a certain college or not. And it actually changes people’s psyche about, “Hey, here’s a policy that tries to look at someone like me and says, ‘I belong,’ is trying to elevate someone like me and people like me going forward in the future.” And as a result of the signaling, these policies have these broad affective kind of effects that can change people’s thinking in ways that impact their health. So in a paper we did, we saw that when affirmative action policies were banned in college admissions, high school students in the state where the policy was banned who were from underrepresented backgrounds reported smoking and using alcohol more.

Suggesting that as a result of depressing hope and expectations, people started to take on health behaviors that in a standard economic model would be considered less forward-looking. That insight was also shown when you look at people’s educational effort in the paper done by some other folks. They found that when affirmative action was reinstituted in some fashion in Texas, that people were investing more in their education, they were studying more, they were going to their guidance counselor and their SAT scores went up. And importantly, these effects materialized even without seeing the opposite effects among people that ostensibly might benefit from repealing affirmative action.

So it suggests that a lot of what affirmative action is doing is not so much mechanically through the college people go to, although that matters, but it also has a lot to do with what we are telling people about themselves and their futures by virtue of passing a policy like this. So that’s really what I wanted to bring out, that social policies matter, that they send signals to people that are relevant to their health behaviors and health. And that policies can impact people even beyond any type of material consequence that they have.

Howard Forman: Can I ask you? You had a paper in the last couple of months in JAMA that to me is very unusual for a medical journal to publish something like this, and it gets to something that Harlan happens to be really passionate about, and that is how sleep can be a mediator of health and how health can be a mediator of sleep and so on. And you published a paper talking about, I believe, that if Black individuals are exposed, meaning that it’s been reported in their area to an officer-involved shooting, that their sleep is impaired. Can you explain, first of all, how does race tie in with that? And second of all, and maybe also explain even how you do a study like this, because I’m not saying I fully understand it, but it is fascinating what I do understand. And then what does this tell us? What can we do about it?

Atheendar Venkataramani: Yeah, so that study was a follow-up of a study we did in 2018, which was published in The Lancet about mental health. And the basic idea was we were trying to gain purchase on this idea of how structural racism causally affects health. And perhaps that’s, now thinking about it, it’s kind of a narrow question. I’m an economist, so I think about cause and effect and what toys can we bring to the table to get a well-identified causal estimate? But the idea was, let’s look for things that happen in the world that reflect structural racism and then let’s trace out how they might impact health. And so police killings of unarmed individuals, I think we as a society generally believe is unfair. And in the Black community, given the history of policing, the history of lynching, and some of the kind of going back hundreds of years, that type of an event has a very particular salience and lands a certain way. Some have even called it modern-day lynching.

And so we wanted to look at when these events happen, they’re often episodic and unpredictable. What happens to people’s reports of their mental health and, in this follow-on study, sleep? And in learning that estimate, it’s not so much about police killings per se, we learn something maybe more generally about how perceptions of structural racism can impact people’s health and wellbeing in the short run. So the goal in many ways is pretty modest, but it tries to get purchase on a larger question in the way that a basic scientist who might have a... a physicist who’s trying to come up with a big theory of the world might try to look at one small slice of the universe to try and understand it. I’m just putting that out there because we want to be modest about it.

To do this study, it’s really interesting because in health we don’t collect data about exposures like this, right? We’re pretty much... we’re collecting data on exercise and smoking and diet, and that’s what we ask about in the clinic. And so we had to marry data from multiple sources. One of the sources is a survey, the Behavioral Risk Factor Surveillance Study, which I’m sure some of your listeners know, but if you don’t, it’s a survey that the CDC does. It’s a random digit dial, so you might get called someday to answer some questions about your health. And this occurs every year; every state does it. So there’s that survey and then some activists had collected some data on police killings of unarmed people. And what we realized is that you’re randomly called in the BRFSS, and you might have been randomly called after a police killing and you might have been randomly called before a police killing. And we can compare those people, because the timing of the call was random, to try and get a sense of does the police killing change what you report in terms of your mental health or your sleep?

And that’s the basic idea of the study. We had to put a lot of bells and whistles in it to kind of make it work statistically. But the concept is pretty simple, and the goal was to really use the small slice of sort of social life to understand something much bigger.

Harlan Krumholz: I was just thinking about the breadth of the work you’re doing. And especially, how you’re investing in promoting the idea of equity and what are the sort of key pressure points within society at the interface of healthcare. And doing it with the lens of your economist background. There was a really interesting piece that you were part of that was also in The New England Journal of Medicine in their “Medicine and Society” section. “Building Black Wealth—The Role of Health Systems in Closing the Gap.” And you made really what I think is a provocative statement. You said, “We believe that health systems that do not address racial wealth gap are abdicating some of their responsibility for improving the health of the country.” And I’d say that that’s a little provocative in the sense that I don’t think most healthcare systems think that’s within the scope of their purview. And yet if they are committed to the health of the populations around them, how could it not be? But it’s not; it’s not part of the conversation.

And I just wonder, just to unpack this a little bit. The obligation to me seems fairly clear: if you are committed to health equity, then you’ve got to seek it in the many of these different ways that it can fundamentally shift the current situation. But maybe you want to explore just with us for a little bit the degree to which this is an important social determinant. And what is it that’s within the power of the health systems to do to try to address it?

Atheendar Venkataramani: Yeah, I think it’s a great question. I think part of this health equity stuff is how do we define equity? What are our social values around it? And a lot of the work I try to do is to say, “If this is our social value, then here are the mechanics of what causes inequity and what we need to address.” And so at some level, I have my beliefs about what it should look like, but we just try to provide parameters that are useful to policymakers with varying beliefs. When it comes to health systems, it’s kind of interesting for me, I think of it in two buckets, right? One is, what do health systems already do? And two is, what are the things health systems could do? So when it comes to what health systems already do, there’s a large segment of the healthcare workforce who are lower-wage workers tend to be from underrepresented backgrounds.

And we know that employment and income are social determinants of health, so health systems are in a position where they can potentially bolster the wages and financial security of folks that work for them that are often drawn from surrounding communities in ways that have salutary benefits. So that’s something that a health system could do. Health systems also, by virtue of their market operations, have impacts on the rest of the labor market that potentially can challenge health equity. So there’s been some work suggesting that when health systems merge because of their increased bargaining power, the prices go up of healthcare, and that’s passed on to everyone else, through a head tax, and comes out of people’s wages. If that is the case, then here’s a situation where, by virtue of standard market operations, we’re basically eroding a certain social determinant of health in the markets that we operate in, right?

So in that case, the ask is for health systems to have a little bit of introspection about what their market operations are and how it might affect other labor markets around them. Health systems have power to procure resources, and they can procure from certain vendors. They can think about what types of vendors they want to go to and potentially promote vendors that are local or come from backgrounds that are generally underrepresented in these types of contracts. So those are things health systems are doing all the time; they just have to think about what’s happening. There’s community benefit spending, so there are ways to kind of make that more evidence-based and targeting places with greater need. That’s the purview of what health systems do.

Where I’m not sure, Harlan, to your question, is health systems are getting into things like housing. And I’m not so sure health systems have the knowledge and knowhow to do that. And so part of what I hope is that health systems start by looking inwards into their own operations and what they can do to bolster their workforce and the labor markets of the communities around them before getting into things like directly intervening on social determinants of health, where I think our expertise is not there. And to the research that really both of you have done, there’s also all the stuff within the clinical sphere that’s been shown where we may not intentionally or perhaps sometimes intentionally treat different groups of patients very differently in ways that are not good for health. Those are also things that we are clearly experts in—clinical care—and where we can, I think, have big impacts. So I would say start inward and work outward.

Harlan Krumholz: So we just keep moving along, though, the disparities remain relatively unchanged over 20 years. We can be calling for things or writing articles. What’s going to be the shock to the system that disrupts what’s currently happening that gets medicine writ large to take greater responsibility for the fact that we’re not just looking at cholesterol and blood pressure, but that the social determinants, the way society is structured, the incentives that are built in have just as powerful an effect on actual health outcomes? And that if we want to fundamentally elevate health, it’s about that design feature of the system and our society that needs the attention, not just chasing the manifestations of poor health as they exhibit themselves as risk factors. And you’re at this stage in your career, you’re still early enough that you’ve got an arc of a career ahead of you, but one of the things that should be keeping you up at night, which is, how do we jolt the system to actually sort of recalibrate and reorient towards what the principal determinants of health outcomes really are?

Atheendar Venkataramani: Yeah. So there is the jolt and then there’s the incremental stuff, and I would argue that the incremental stuff is definitely already happening. In terms of the jolt, I think it’s getting people behind the narrative, regardless of what their theory of justice is, but getting people behind a narrative that the way the social world shapes our abilities to self-actualize and to function and to flourish is incredibly meaningful and important for our health and wellbeing. And I think people at some level get that. Rourke and I are trying to write a book, actually, that tries to build another narrative to try to bring together very disparate sets of population. So there are people who care about structural race and there are people who care about the health effects of labor market shocks, there are people who care about immigration and health. And we’re trying to basically say these are all the same thing because all of these different forces affect people’s opportunities. And so we should be thinking about an opportunity-centric or a society that prioritizes opportunities.

So I think some type of big narrative shift is what’s needed so that people can see that their specific health problems are actually related. And it goes from saying, “Hey, this isn’t fully, or even really any your fault, but that communities and society have a responsibility to keep people healthy.” So I think people need to really internalize that we’re still a culture that thinks about health in a very individualistic way, whether it’s behaviors or technology. So that’s the big jolt that needs to happen. It’s hard to do—we will keep trying.

But in terms of incrementalism, things like recognizing that the health consequences of social policy should be scored in legislation and accounted for as a benefit. So there are economists and other folks who have developed tools to basically internalize the overarching consequences of a given policy into a single number so that people can make choices about whether to invest or not invest. That’s something that’s already happening. The idea that social policy matters in general, that’s also something that’s happening with, I think, now every few months there’s an article about life expectancy and why things are going so poorly in the United States. I think there’s a recognition in that that the social world matters.

And so I think incrementally compared to when I started working on this opportunity stuff in 2015. When I said that opportunity matters for health in 2015, the first paper we wrote on this, it took eight tries to get it published. And now I’m seeing in surgery journals, people using economic opportunity as a driver of surgical outcomes, right? We have come a really long way in our understanding. And so incrementally it is progressing, Harlan, but I think we need this big narrative shift away from kind of blaming individuals to thinking about the structures we live in and how to optimize them for everybody.

Harlan Krumholz: Yeah, I love that. Moving away from blaming individuals and understanding the forces around that are built. That’s great.

Howard Forman: That was great.

Harlan Krumholz: Thanks so much, it was wonderful to have you.

Howard Forman: It’s great to see you.

Harlan Krumholz: It’s such a delight to hear your perspectives.

Howard Forman: Thanks for joining us.

Atheendar Venkataramani: Yeah. Thank you so much for having me, this was really fun. Really appreciate it.

Harlan Krumholz: Well, that was a terrific interview. I love it. He set up this center,<start> and he’s really talking about, like you said, this connection between the American Dream and people not able to achieve it, hope and opportunity and how he can bring his economic skills. Just terrific, just terrific.

Howard Forman: Yes.

Harlan Krumholz: But let’s get to my favorite part. I love the other parts, but my favorite part is hearing from you. So what’s on your mind this week?

Howard Forman: Yeah, so it relates to some of what you talked about in the intro, but I’ll just start here. Stock prices tell us a lot about the success of companies. They’re not perfect, but they tell us a lot. And we have talked on this podcast about the enormous returns that Humana has made and the poor returns of Bluebird Bio, the company treating sickle cell, have had. So we’ve talked about stock returns before. From a finance point of view over long periods of time, stocks relatively efficiently price in all available information. So when a stock increases over long periods of time, it indicates its prospects have improved. And when they decline over long periods of time, their prospects are generally in decline. So there’s a lot of reasons why this may happen. It’s not necessarily due to bad management or good management, but things happen. But we can learn a lot from looking at stock prices, and we can learn a lot in the pharmaceutical sector here. And we can compare the pharmaceutical sector to average stock prices like the S&P 500.

So I decided, let’s just look really briefly at a select group of pharmaceutical stocks starting November 19th, 2019. I chose that date because that’s the first date before COVID became even leaked, before anybody had a clue COVID was going to come out. So I wanted to know, how did drug companies do since COVID? And by the way, the S&P 500, the overall stock market is up about 67% since that date. And what’s the stock most identifiable with COVID therapeutics and vaccine? I think it’s Pfizer. That was where the vaccine, it’s where Paxlovid came. And it by the way is down 27% since that date. And Merck, another stock identified with COVID, up but only by 55%. And AstraZeneca, another COVID stock, another vaccine stock, only up 42% again, versus 67% for the average stock in the market. So in all these cases, stocks are underperforming. These stocks are underperforming the overall market.

So with relatively rare exceptions, the pharmaceutical industry has not been a great place to make a lot of money. But as you know, there are two major companies that have surprise to the upside. You talked about them in the intro, Novo Nordisk and Lilly. Eli Lilly is up an astounding 560% during the same interval. And Novo Nordisk is up a mere 364%. Seemingly all of the hot money in life sciences is going toward GLP-1s and other anti-obesity drugs. And every day, including today on your intro, we learn not only of greater efficacy for treatment of diabetes and obesity but increasing evidence that they reduce inflammation, reduce heart disease, even might slow the progression, as you mentioned, of Parkinson’s disease.

I am not sure any drug category has ever had so much promise and so much already proof of concept. But a reminder to our listeners that this is not a new category; GLP-1 receptor agonists, the Ozempic, Wegovy, Tirzepatide, so on, were approved 19 years ago this month. I had to go back and look at that. The first GLP-1 was approved 19 years ago. It has taken us this long to learn all that we’re learning, and we still have a way, way more to go.

So I want to make just a couple of quick summary points. One, I think we vilify the pharmaceutical industry too much. It is clearly profitable, but our relative spending on drugs has been stable for about 35 years. And if it was such an easy way to make a lot of money, I think more people would be chasing it. Two, I think it takes a long time to generate the science and evidence that changes lives. And so while Lilly and Novo Nordisk appear to have hit the winning lottery ticket, they built the success on the shoulders of a lot of innovators, a lot of basic science researchers, and a lot of current clinical trialists. And much like with statins, the first movers were not the biggest winners. And lastly, the market for these drugs is still maturing. We’re going to see oral formulations, cheaper options, more long-term studies, and hopefully we’re going to really truly impact on a global and population basis, obesity and other diseases in a way that we’re just beginning to pray for at this moment. So I think we’re going to keep coming back to this. I know this has been a topic of great interest to you, but it’s just a good time to reflect on the fact that the pharmaceutical industry is basically one industry that’s not doing so great and another industry that’s just going bonkers.

Harlan Krumholz: Well, stock prices have everything to do with psychology and what’s hot. In the same way that generative AI, you mentioned generative AI and their investments and things are off the charts, the expectations are high. But I couldn’t agree with you more, and it’s just very interesting to track. Some of the fundamentals I think get lost when there’s exuberance. What do they call it? What did he say?

Howard Forman: “Irrational exuberance.” Yeah.

Harlan Krumholz: …”irrational exuberance” about some things. I will say, I think these anti-obesity meds may not be irrational exuberance, I think that may be justifiable exuberance. The onus will be on society to figure out how they can make them accessible and ensure that everyone who can benefit will. At the meeting I was at, people were standing up and going, “Will people in 100 years ago be saying, ‘There was a country that overfed its population and then had to create medications to address the overfeeding.’” I don’t know what to say. We live in a country, in many countries where there’s an abundance of different kinds of foods that people crave. And you can urge lifestyle modification, but in the end, I think in the context of a society like ours, obesity becomes a disease that needs to be treated. And—

Howard Forman: I agree. Look, there are people who are obese who eat healthy foods and only healthy foods. So it’s not just about what food companies are doing. At a certain point, there are some central and other physiologic changes that you have to tackle.

Harlan Krumholz: Exactly. There are people with obesity, and we have failed to demonstrate that the lifestyle modifications have sustainable....Anyway, I’m not sure it’s irrational because I think it’s amazing, and I can’t wait to see what other empiric evidence we have or what else they do. We just need to continue to monitor them for harms because long-term use, we don’t know. Although people with diabetes have been using them for quite a long time—

Howard Forman: That’s right.

Harlan Krumholz: ... so we have some confidence that it’ll be okay, but I think that’s great. Howie, thanks so much. You’ve been listening to Health & Veritas with Harlan Krumholz and Howie Forman.

Howard Forman: So how did we do? To give us your feedback or to keep the conversation going, email us at health.veritas@yale.edu, or follow us on any social media, LinkedIn, Threads, or Twitter.

Harlan Krumholz: And we want to hear your feedback, questions, or your own experience with these topics. And however you feel about us, feel free to leave a review on your favorite podcast app, we always read them and learn from them. We just got one from StephQ44 that was very congratulatory. Thank you, StephQ44.

Howard Forman: Yeah. No, we appreciate it. We do read it, and it’s obviously available. Anybody who wants to look on Apple Podcasts, the review is there, but we appreciate it, Steph.

Harlan Krumholz: And what should people do if they have questions about your MBA program?

Howard Forman: Well, and if you have questions, please do reach out via email for more information or check out our website at som.yale.edu/emba. And some exciting news to share with our listeners, we’re going to do a live podcast taping at the Yale Innovation Summit on May 30th at Yale University at the School of Management. Link’s in the show notes today; we’ll keep giving you updates on this. But come to the Innovation Summit and see us interview some of the greatest health and technology innovators.

Harlan Krumholz: Is there going to be a delay in case we say something wrong?

Howard Forman: I hope so, but you never know.

Harlan Krumholz: You never know. Health & Veritas is produced with Yale School of Management and the Yale School of Public Health. Thanks to our researchers, Ines Gilles and Sophia Stumpf, Yale undergraduates who are just amazing, and our producer, Miranda Shafer, who somehow makes us sound good every week. Thank you, Miranda.

Howard Forman: Yes.

Harlan Krumholz: Talk to you soon, Howie.

Howard Forman: Thanks very much, Harlan. Talk to you soon.