cover of episode 615. Is Ozempic as Magical as It Sounds?

615. Is Ozempic as Magical as It Sounds?

2024/12/12
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Ezekiel Emanuel
节目旁白
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节目旁白:介绍了GLP-1类药物,特别是Ozempic,在减肥和治疗糖尿病方面的巨大市场需求和高销售额,以及其价格昂贵和保险覆盖范围差异大的现状。 Ezekiel Emanuel:详细阐述了GLP-1类药物的研发历史、作用机制、多种益处(包括降低血糖、减肥、保护心脏、肾脏和肝脏等),以及潜在的副作用(例如胃肠道不适和胰腺炎)。他强调了这些药物的益处超出预期,并对未来应用前景表示乐观。同时,他也指出对药物对成瘾和精神疾病的影响仍需进一步研究。 节目主持人:就GLP-1类药物的益处、副作用、长期影响、以及临床观察的可靠性等方面与Ezekiel Emanuel进行了深入探讨。 Ezekiel Emanuel:就GLP-1类药物的成本效益分析、医疗保险体系的缺陷、以及道德风险等问题发表了看法。他认为,现有的医疗保险体系不利于长期投资,导致GLP-1类药物的分配不公平,富人更容易获得这些药物。他建议采用订阅模式,以确保更多符合条件的人能够获得这些药物。 节目旁白:总结了不同国家对GLP-1类药物的报销政策差异,以及美国医疗政策在该问题上的复杂性。 Ezekiel Emanuel:分析了美国医疗体系的现状,并对《平价医疗法案》的成就和不足进行了评价。他认为,该法案在扩大医疗保险覆盖范围方面取得了显著成效,但在控制医疗成本和提高医疗质量方面仍存在不足。他呼吁对医疗体系进行改革,以更好地满足人民的医疗需求。 节目主持人:就人工智能在医疗领域的应用前景、远程医疗的利弊、以及癌症治疗的进展等问题与Ezekiel Emanuel进行了探讨。 Ezekiel Emanuel:表达了对人工智能在医疗领域应用前景的乐观态度,并阐述了其对医疗资源分配、儿童健康投资和医疗成本控制等方面的建议。他还讨论了远程医疗的利弊,以及医疗执照制度的改革。他认为,远程医疗能够改善偏远地区居民的医疗服务可及性,而医疗执照制度的改革则有助于促进远程医疗的发展。他最后还讨论了癌症治疗的进展,以及肠道微生物组对癌症的影响。

Deep Dive

Key Insights

Why are GLP-1 drugs considered "miraculous"?

GLP-1 drugs, like Ozempic and Wegovy, effectively treat type 2 diabetes and obesity. Wegovy has shown a 15-16% weight reduction, while Mounjaro, another GLP-1, has demonstrated a 21% weight reduction. Beyond weight loss and diabetes control, these drugs show promise in protecting against heart disease, kidney disease, cirrhosis, and potentially have positive effects on mental health and addiction.

What are the potential downsides of GLP-1 drugs?

Common side effects include nausea, diarrhea, constipation, and a feeling of fullness. More serious, though rare, side effects include pancreatitis. Cosmetic side effects like a hollowed-cheek appearance and wrinkles are also possible.

Why is the brain effect of GLP-1 drugs so remarkable?

These drugs, large proteins, appear to cross the blood-brain barrier and influence mental states, impacting areas like addiction and psychiatric conditions. This effect was unexpected and the mechanism is not yet fully understood.

Why is government involvement crucial for clinical research on drugs like GLP-1s?

While pharmaceutical companies play a vital role in funding large clinical trials, their primary interest lies in comparing their own drugs against competitors. The government, through institutions like the NIH, should focus on comparative effectiveness research across different drug classes, serving the broader public health interest.

Why is the current U.S. healthcare system not incentivized to make long-term cost-saving investments in drugs like GLP-1s?

High patient churn in the insurance market, due to job changes and other factors, creates a short-term investment horizon for insurers. They are less likely to cover expensive drugs with long-term payoffs, like GLP-1s, as the cost savings will likely benefit a different insurer in the future.

Why does the price of GLP-1 drugs vary so much internationally?

The Lancet paper reveals a wide range in GLP-1 drug prices, from $283 in Japan to $1350 in the U.S. This suggests pharmaceutical companies adjust prices based on negotiations with governments and other payers, indicating potential for price flexibility.

What are the ethical considerations surrounding GLP-1 drug coverage?

Given the high cost of GLP-1 drugs and varying coverage policies, access is often limited to wealthier individuals. This disparity raises ethical concerns, as those with obesity and diabetes who could benefit most are often unable to afford these potentially life-changing medications.

What are Ezekiel Emanuel's top priorities for reallocating healthcare savings?

Emanuel prioritizes investment in children, from early childhood through pre-K, to maximize social benefit. He also advocates for capping out-of-pocket healthcare expenditures for families and investing in infrastructure improvements.

Why is state-based medical licensure problematic in the context of telemedicine?

State-based licensure restricts access to specialists via telemedicine, particularly for patients in rural areas. National licensure would enable patients to connect with specialists across state lines, improving access to care.

What is the connection between the gut microbiome and the rise in certain cancers among younger people?

Changes in diet, particularly the consumption of ultra-processed foods, may negatively impact the gut microbiome. This shift in gut bacteria could potentially contribute to the development of cancers like colon cancer at younger ages.

Chapters
This chapter explores the rise of Ozempic and other GLP-1 drugs, their mechanisms, and unexpected effects beyond diabetes treatment, including weight loss, and potential impact on addiction and mental health. It also addresses the skepticism surrounding these drugs and the need for further research to understand their long-term effects and potential side effects.
  • Ozempic is a GLP-1 drug that mimics a hormone in the human gut.
  • GLP-1s have shown surprising effects on weight loss, addiction, and mental health.
  • Concerns exist about the long-term effects and potential side effects of GLP-1s.
  • The effectiveness of GLP-1s in treating addiction needs further investigation.

Shownotes Transcript

Translations:
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The United States is one of just two countries that allow pharmaceutical firms to freely advertise their products directly to consumers. The other is New Zealand. So if you ever watch TV in the U.S., you have likely seen many ads for prescription drugs.

But advertising doesn't guarantee success. The research and development of these drugs is very expensive, and most of them never earn back their investment. The pharmaceutical industry, therefore, relies on the occasional blockbuster drug, a blockbuster defined as doing more than a billion dollars a year in sales. If I asked you to name a blockbuster drug from the past, you might say Lipitor, a statin originally from Park Davis,

or Humira, an anti-inflammatory now sold by AbbVie. And can you name a current blockbuster? The first drug that comes to mind might be this one. If you watch even a tiny bit of TV, you've probably seen an ad for Ozempic. Their jingle is sung to the tune of the 1974 pop hit Magic by a band called Pilot, which had exactly one U.S. hit. ♪

Ozempic, which is sold by the Danish multinational Novo Nordisk, is not a one-hit wonder. It is one of a group of drugs known as GLP-1s, and many Americans would agree that they are magic.

GLP stands for glucagon-like peptide, which is a hormone produced in the human gut. And these drugs mimic the activity of that hormone. Ozempic was developed to treat type 2 diabetes, which used to be called adult-onset diabetes, to distinguish it from the more serious type 1 diabetes, which most often occurs in young people.

But those lines have blurred as many more people around the world, including a lot of young people, are now getting type 2 diabetes. Diabetes is a condition whereby the pancreas can't produce enough insulin to modulate your level of glucose or blood sugar. Over the long term, high blood sugar can lead to all kinds of problems. So any drug that could help the body produce more insulin would be a blockbuster. Enter Ozempic.

But wait, there's more. Ozempic and other GLP-1s don't just lower blood sugar. They also help patients lose weight, primarily by slowing digestion and decreasing appetite. This secondary discovery, weight loss, was a big deal, especially in the U.S., where more than 40% of the adult population is obese.

Even though researchers don't know much about the long-term effects of GLPs, whether they remain effective over time, whether they have serious side effects, the take-up has been enthusiastic.

Ozempic and Wagovi, another GLP drug made by Novo Nordisk and which is authorized to treat obesity, will do a combined $65 billion in global sales this year. Novo Nordisk is now worth more than the GDP of Denmark.

And Novo Nordisk isn't the only company making blockbuster GLPs. Another big one is Mount Jaro, which was brought to market in 2022 by the American pharmaceutical firm Eli Lilly. Mount Jaro works by mimicking two digestive proteins, GLP-1 and GIP. Most of these new drugs are, for now, injectables, although that will change and some are already in pill form. And these drugs aren't cheap, at least not yet.

In the U.S., they can cost more than $1,000 a month. And as we will hear today, insurance coverage varies widely.

Still, more than 15 million Americans are already using these drugs. So is the magic real or maybe too good to be true? I think your skepticism is well placed, and that's why we do trials to find out. Today on Freakonomics Radio, we continue our December of one-on-one conversations with Ezekiel Emanuel, who is

Pretty excited about these GLP-1 drugs. This is why people do science, because you discover something and then lots of unexpected effects happen. Emanuel is an oncologist, a medical ethicist, a professor and a health care policymaker. He helped design the Affordable Care Act, better known as Obamacare. He also worked on health care policy in the Trump White House.

In today's conversation, we talk about why many insurers don't want to cover the GLP drugs. We've created a system that perfectly disincentivizes long-term investments. We talk about progress in cancer treatment, mysteries in the gut microbiome, and flaws in the U.S. healthcare system. Don't get me started. We got to have a whole other conversation about that issue.

And we talk about what health care policy looks like in a second Trump term. Even Republicans want everyone to have health insurance. We're not repealing the Affordable Care Act. All that and quite a bit more with Zeke Emanuel, starting now. This is Freakonomics Radio, the podcast that explores the hidden side of everything with your host, Stephen Dubner.

If the last name Emmanuel sounds familiar, it may be because Zeke Emmanuel has a couple of brothers

who over the years have also appeared on this show. There's Rahm Emanuel, former Obama chief of staff and Chicago mayor, who was serving as U.S. ambassador to Japan when we spoke with him in 2023. Rahm is known to be smart, tough, and reliably combative. You know what? Don't ask me that, Stephen. I don't really like that question, okay? That episode was called The Suddenly Diplomatic Rahm Emanuel.

Then there's Ariel Emanuel, who runs the entertainment and sports firms Endeavor and TKO. His business is high profile, but for himself, he tends to keep a lower profile. This may date back to his childhood as the youngest brother in a very competitive household. Ari thought of himself as the dumb one. You know, the grades would come up, our report cards, on the fridge.

I was competing with Zeke. There was no chance. Dean's list. He was the debater. Shut up. That episode was called Ari Emanuel is Never Indifferent. Zeke Emanuel is the oldest brother, the one who took the trouble to write a family memoir called The Brothers Emanuel. He leans more toward collaborative than combative.

He has also been on Freakonomics Radio before, most recently in an episode called Who Gets the Ventilator, which we published early in the COVID pandemic when ventilators were thought to be an effective frontline treatment.

Here's a clip from that episode. If it sounds like it was recorded in a closet because of COVID, it probably was. First come, first serve is the absolute worst principle you can think of in this situation. That was a really interesting conversation about how medical resources should be allocated in times of scarcity. In the case of ventilators, the scarcity was caused by lack of physical supply.

In the case of this new generation of GLP-1 drugs, there has been some supply shortage, but the scarcity for many would-be patients is caused by their high prices. High prices and inadequate coverage in the healthcare industry are always a topic of great concern, as we've seen lately in the fallout from the murder of Brian Thompson, the CEO of the insurance firm UnitedHealthcare.

I knew that Zeke Emanuel could give us a 360-degree view of the GLP revolution. So I began by asking him when he first became aware of these drugs. Maybe in medical school? No, I did not come across them in medical school, even though I went to Harvard Medical School and a lot of the early work was done at the Massachusetts General Hospital. Which is a Harvard-affiliated hospital. Exactly, just down the block.

One of the groups at the Mass General Hospital was taking pancreases out of fish and then testing how do they affect glucose in other models. And they ran across what's called the proglucogon, a very long protein that makes glucagon, but it also makes the GLP-1 agent that affects the glucose levels in the blood.

It was the 1990s when they showed that GLP-1s normalized blood sugars. That was really important. And then in 1996, researchers in Britain identified that the GLP-1s caused a loss of appetite in

Jens Holst in Copenhagen worked with Novo Nordisk, which is one of the big pharma companies that has produced insulin and was very active in the diabetes field to make the first GLP-1 drug for diabetes. That was done by a woman named Lottie Knudsen. In 2010, they created that first drug,

And then in 2014, the indication was expanded to obesity because they saw that, you know, diabetics also lost weight. The GLP-1s from Novo Nordisk, Wegovia, or Ozempic, they are really impactful both in terms of decreasing weight. With Wegovia, you get about 15%, 16% weight reduction, but also very good at bringing down blood sugars for diabetics.

And then when you add the other component, the GIP, Mongero, that's the Lilly drug, you get even more weight drop, 21%. And we know that Wagovi, the GLP-1, has a lot of other effects, specifically.

It protects the heart, a 20% drop in severe cardiac death from heart attacks, number of heart attacks, strokes goes down 20%, which is pretty amazing. It protects from severe kidney disease. It protects from cirrhosis.

And we've got hints that there are lots of other effects, psychiatric effects, addiction. You've mentioned depression. I was going to say addiction. You beat me to it. Cancer, even because obesity and diabetes are associated with increased risk of cancer.

Honestly, as you describe that, Zeke, it sounds like this class of drugs is too good to be true. You've called them a miraculous set of drugs. Before we get further into the upsides, what about downsides now?

and or side effects. As I like to say, even a blood test has side effects. The major side effects tend to be with the gastrointestinal tract, as you might expect. Nausea tends to be at the top of the list, diarrhea, constipation, some fullness because it slows emptying of the stomach,

About a quarter of people have these side effects and it's variable in how much people experience it. I've talked to people on these drugs and they have it minimal. I've talked to other people and they have quit the drugs because they really found it intolerable. As you're describing the multiple uses, treatment, but also prophylactic for all these different conditions.

It sounds almost as if you would recommend that these drugs go in the water supply. No, I don't. I am very enthusiastic, but there are some more serious side effects. One of the most serious is pancreatitis. That is inflammation of the pancreas can cause severe abdominal pain and other problems. It's pretty rare, but it's not

unheard of. There's also some cosmetic side effects. When you lose the fat out of your face, you can get this sort of hollow cheek look and a lot of wrinkles. So I do think these could be more widely used, especially for people with obesity.

But unlike some other drugs that I do think probably need to be in the water supply, these need to be used a little more selectively. I'm curious how you and others foresaw how useful they'd be, not only for weight loss and diabetes, but potentially all these other treatments. I'm curious what your view of them was like, what the skepticism was like, and who's skeptical now, maybe. First.

First of all, I was not fully focused on how beneficial they could be. I have to give credit to Novo Nordisk and Lilly for doing trials that didn't just look at diabetes or didn't just look at obesity, but looked at more outcomes. And for the clinicians who identified, wow, we're seeing these other positive effects.

people eating less, the addictions to alcohol and drugs going down. I'm sorry to interrupt, Zeke, but on something like that, when you're talking about clinical treatment, doctor treatments, and they're saying they're observing that their patients are having fewer problems in these other realms, whether drinking, eating. I mean, how empirical is that? Because I could imagine that someone who feels like they are improving on one dimension of their life

maybe changes their behavior in response to positive feeling and kind of not quite placebo, but something that was spurred on by one positive effect that has these other positive knock on effects as opposed to actually treating addiction and so on. I think your skepticism is well placed, and that's why we do trials to find out. We're in a huge number of trials.

On the other hand, there are some things like, you know, looking at livers. How does the liver change with these drugs? That's not going to be a placebo effect. That is actually going to be a drug effect on something like addiction, especially things like alcohol and drugs, where we know it's so hard to stop.

When you do see lots of people on these drugs stopping and reporting that they don't have the craving, you have to take that seriously. That doesn't mean it can't be a placebo effect, but it affects the gut. It affects the pancreas to increase insulin. And it obviously has to affect the brain if it's going to affect these addictions and psychiatric situations. And that's what is probably the most remarkable and unexpected thing.

finding here that this big protein somehow is getting across the blood brain barrier or somehow is being released there and being able to affect people's mental situation.

On all the reading I did on this, and I have to admit, a lot of the science is really hard for me, at least, and maybe many lay people to understand. But it sounds as though there are a couple different mechanisms or maybe different drug classes work in different mechanisms. But it sounds as though there is a body effect, a kind of cellular body effect and a brain effect. Is

Is one drug causing both of those or are they different drugs that do that? Well, we don't know for sure, but probably the same drug or some way that it's causing a pathway effect. But that's not understood yet, you're saying fully. Especially the brain effect.

Sometimes, you know, great things happen that have multiple applications. Since the end of the genome project in roughly 2000, we've had five big breakthroughs in healthcare. We've had CRISPR where you can edit genes. We've had gene therapy where you've, you know, I use this term, the researchers are a little more cautious, you know, really cure blindness. We've had CAR T therapy where, again, the researchers are a little more cautious, but you cure people of cancer who are on their deathbed.

We've had the mRNAs, and now we're, you know, multiple uses for mRNA items, not just vaccines, but in many, many other ways. And you've had these GLP-1s. Each of these have way more ramifications than we ever thought possible. Let's take a step back on that front and talk about where research funding and research incentives are coming from these days. The five treatments that you've just named are evidence of how...

how things are working in medical science. As we all know, a lot of these routes are very meandering. They take a long time. There are all kinds of failures and dead ends when you're doing this kind of research. How do you feel about the current state of moonshot medical advances? And I'm especially curious to know how you would assess the private-public collaboration there. First of all, let me say we need public and private collaboration because each part does different things.

Mainly, the government invests a lot in basic research and tries to create understanding of how these pathways work. And let's be honest, deciding what you're going to fund is based upon judgment of the community and the community, like any community, has prejudices.

It's pursuing one avenue rather than all the avenues. And we know that sometimes has been an inhibition to good and high-risk research. The government often doesn't like to have failures on research. One of the criticisms I have is the government has more or less ceded most of the clinical research to drug companies. Now, drug companies obviously have a big investment.

but they have a particular kind of investment. Comparing different drugs in the same class or comparing one drug like GLP-1s with another drug like the SGLT-2s that might be used for diabetes, that's not so much in their interest unless they think they're going to easily win that race. But the government should be doing a lot of that comparative assessment. And yet the NIH has gotten

It's not out of clinical research, but it's reduced its footprint in clinical research a lot. And that, I think, is a bad thing. You know, we need drug companies. They can fund these big trials, but we have to recognize they have their own interests at heart, which don't necessarily correspond to the national public health interest.

We've got to have them because they know how to scale. They know how to market the drugs. They know how to chemically adjust the drugs to increase how long they last in the body. We can't underestimate. Convenience is really important because for a chronic illness, you have to stay on the drug often forever. I've heard you say that one big problem with medicine today is that 86% of all spending goes to chronic conditions. In the case of the GLP-1 drugs...

widespread adoption would, I assume, over time bring down those costs dramatically. I know we're talking about high costs in the short term, but I assume in the long term, the costs would fall a lot. First of all, tell me if that's indeed the case. And second, if you look really big picture,

how you think about all that money potentially being reallocated to research, treatment, prevention, cure, etc.? Well, Stephen, let's be clear with the listener.

We have to separate out something that is cost-saving, we pay for it now, but it'll save money over time, from something that is cost-effective, which means the total amount we pay is still worth it, but it doesn't save money. So far on the GLP-1, the cost analysis does not show us saving money.

But I think you're right. We've got 42% of the adult population obese, 20% of U.S. children obese, 10% of the U.S. adult population has type 2 diabetes. If we can treat those illnesses, reduce things like hospital admissions, hypertension, cardiac disease, kidney disease, the liver disease that goes with them, maybe we will be able to save money. Here's the problem.

Even if we could show that over a 10-year time horizon, they were cost-saving, that society would get back more money than we paid for the drug by saving other medical costs, hospitalizations, other drugs, replacement of hips and things like that.

We've created a health care system where it's not in the system's interest to make those long term cost savings. What do you mean by that? You're talking about the incentives of the insurance companies? Say you're sitting at United or Humana or a Blue Cross and Blue Shield insurance.

You have a person, call them 30 years old, who you're insuring. You're going to spend money today for them. And the payoff is going to dribble out in five, six, seven years when they've gone for a long time with their diabetes under control or they've gone for a long time ceasing to be obese. The problem is by the time those positive benefits come and the cost savings come, they're no longer being insured by you.

We call this in the medical health policy world churn. The churn is so much in the insurance market that that investment horizon for companies is not five, six, seven years. It tends to be one year and maximum two years.

Is that primarily because health insurance is tied to employment in this country? That's a large reason for it. People change jobs, lose jobs, move. They get married and they switch from their insurance to their spouse's insurance. We've created a system that perfectly disincentivizes long-term investments. And that's bad when chronic illness is the main source of costs.

So we're going to have to change how we structure the insurance marketplace. And no one's talking about that at the moment. OK, let's us talk about it. My conversation with Zeke Emanuel continues after the break. I'm Stephen Dubner, and I'd like to thank you for listening to Freakonomics Radio. Not just today, but always. We'll be right back.

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We've been talking with the oncologist and health care policymaker Ezekiel Emanuel about the large and sudden uptake of GLP-1 drugs, which were designed to treat diabetes, but have also been found to have other effects. They help people lose weight, drink less, even have more sex drive.

This GLP revolution will no doubt produce a variety of downstream effects, not just physiological and psychological, but political and economic effects. There will be behavior change and social change. What will all these changes look like?

I have no idea. And no one else does either. If they say they do, you should start walking in the other direction. Predicting the future is hard. Uncertainty is real. And as we often preach on this show, unintended consequences can be powerful. So let's plan on following those long-term effects as they unspool. But for now, let's get back to the near-term effects of these drugs.

One big problem with GLP-1s is that they are expensive. So a big question is who pays for them? What is the responsibility of health insurers, whether we're talking private firms or government plans? How much should any government directly subsidize these drugs and how much are these drugs worth to society?

These are some of the questions that Zeke, Emanuel and several colleagues tried to answer in a recent article published in The Lancet, a prominent English medical journal. They offer, as their subtitle says, a review and ethical analysis of discordant approaches. I asked Emanuel why he took on this project.

The prior article we published in the New England Journal was about how to ethically allocate the resources of the GLP-1 drugs. And we established a framework that puts younger obese patients at the top, along with diabetic patients who aren't responding to other treatments.

And so we had the natural question, what are other countries doing? You know, we always look to other countries who think they've got to have a better system. And one of the things you learn is, well, the Germans, they got the same allocation as we do in Medicare. They don't cover any of these weight loss drugs. Then you stumble upon other countries like Australia and Denmark, and they say, oh, these drugs aren't cost effective. But in fact, they

They use long outdated cost effectiveness before all the benefits for heart disease and liver disease. Long outdated, you mean just like 2022, two years ago. Exactly. But, you know, in a rapidly changing field, you have to be nimble and you have to use the absolute latest data. And then we see a whole series of countries where they're worried about the total cost and they're just saying we're not covering it, which is the wrong perspective.

Drug prices might be high, but there are some people who need the drugs more than other people where the benefits are going to be greater. You should cover it for those people. And let's remember,

these aren't the only expensive drugs in the marketplace I'm an oncologist every oncology drug is super expensive none are cheap unless they're generic we cover those and their benefits are probably way less than Ozempic or Wagovi or Monjuro because with cancer drugs you're sometimes talking about a life extension of just weeks or months versus potentially many years with these GLP-1s the life extension for a severely obese patient could be 5 to 10 years and that's real

Here are some key statistics from the Lancet paper. Emanuel and his colleagues analyzed GLP-1 policy in 13 high income countries, including the U.S. and the U.K. All 13 of them cover the cost of GLP-1s for at least some people with type 2 diabetes. But nine of the 13 countries deny reimbursement for weight management.

The U.S. is perhaps the most hodgepodge of these 13 countries, given its mix of federal, state and private health care coverage. I asked Emmanuel to start from the beginning and describe just how much variance there is from place to place. Well, almost every country covers it for diabetes, but we've got a lot of countries that don't cover it at all for weight loss. Australia, Belgium, Denmark, Finland, Denmark.

Germany, Italy, Israel. Okay, don't cover it. Canada also doesn't have a national policy, so it's a little more variable. Of the 13 countries, four, France, Iceland,

Japan and then the UK, under some conditions, cover Ozempic, Wagovi, Monjuro. And the conditions vary. So France, you have to have a high BMI or a slightly lower BMI and severe comorbidities from obesity. The UK, you also have to change your diet and exercise. And then there's Iceland, which says, look,

We'll cover it, but you're going to have to have serious weight loss. If you're not actually losing weight, we're going to not cover it.

So that you can get started on it, but if you haven't lost weight within a certain time, your coverage will be pulled, essentially? Exactly. And, you know, if I had to pick one, I would say I like what France is doing, and I like what the UK does in terms of it's not just about drugs, it's about a whole lifestyle change and give people help with doing that. I think those are the right directions to go. Since you and I and much of our audience are American, and since Americans are particularly solipsistic... Ha ha ha ha!

Let's talk about the American circumstance with coverage, but also price. So one thing I learned from your paper is that the prices charged for GLPs in different countries vary massively. I believe it's around 280 some dollars in Japan to thirteen hundred and fifty dollars in the US. First of all, it shows you that there's price flexibility, that these drug companies are willing to change the price depending upon what governments or others require.

Was that your brother who negotiated the 283 in Japan, you think? He is a good negotiator. I'll say that. He's also a cheapskate. I'll say that too. So I think that's actually a positive.

That makes me optimistic. And if I were in charge, if I were the health czar in the United States, I would go to these drug companies and I would say, listen, let's get a subscription model. We're going to give you a flat fee so you make money and you're going to give us an unlimited amount of these drugs because actually to produce these drugs is not that expensive. And we're going to try to get everyone we can who qualifies.

on these drugs. That's a deal I think everyone could be happy with. The drug company will make a lot of money and the country will be able to treat more people and we'll be better off.

off. It won't also be just to first come, first serve if you've got a lot of money. What is a budget that would be reasonable to spend on people with obesity and diabetes? That's our limit for spending. And it's probably going to be pretty good given, I think it's, last I looked, $173 billion we spend on obesity-related healthcare. So

We have tens of billions, you might say, we could spend. So we could make it enticing for a drug company, but also good for public health.

Economists, as I'm sure you know, like to talk about what they call moral hazard, which is if you make some behavior less costly by insuring it or protecting against it somehow, then people are freer to do it. So I'm thinking, well, if I can now have my GLP-1 that is going to keep my weight down, prevent diabetes and prevent all these other potential complications, then I'm going to be able to do it.

heck, I can eat whatever I want, whenever I want, because medicine has helped me out. But there's also the idea that food is medicine, right? That nutrition is important well beyond the weight component. So having permission to eat garbage calories would be at best a partial victory. So how do you think about that balance? Here's a positive. We have focused more on obesity and we've also understood better that it

is not simply a lifestyle choice. It has to do both with the body, and therefore it's very biologic, and it has to do with our social environment, the food. You know, today we have 20% of our children are defined as obese and 16% is overweight. And within that obese category, 6% are severely obese. That is a terrible place to be. We've got type 2 diabetes in young kids, hypertension in young kids.

We have to reverse that. And that isn't going to be a Manjaro or Wagovi or Ozempic solution. That has to be a solution of changing their diets and getting them more exercise. There's just no alternative to that. We need to invest more in the public health of our children and encouraging their parents to change their diet and maybe more than encouraging using things like taxes and

other mechanisms, school lunches, school breakfasts, to change that behavior. I mean, this is a song I've been hearing for probably 20 or 30 years now. Absolutely. But, Steve, because so much attention has been focused on obesity now because of these drugs,

And because we can realize, oh, you can change that by giving a drug that must be a biological thing. It's not simply a weakness of will that you're eating more. I'm hoping that changes our culture around obesity. And look, when I started thinking, well, we've got a limited amount of these GLP drugs. Who should get the GLP drugs? When I started doing that research, my thinking was it's got to be the diabetic patients. They're going to benefit the most. And then

I get into this and I begin thinking, all right, what are we trying to do? We're trying to save the most lives. And then I said, well, who loses the most years of life? It turns out it's the people with obesity. My own analysis changed my ethical judgment here. When you look at these data.

The people who are really suffering are people with obesity. They're the people who are going to benefit the most from these drugs. Most insurance companies don't want to cover it because it's a big expense. Medicaid is all over the place. Some states are covering it. Most states are not. The consequence is, you know, who's getting GLP-1s?

Rich people. That is the totally unethical, unjust way of allocating these very important pathbreaking drugs. We have to change our system so that we actually do the ethical thing. And that so far is not where we're headed.

We recorded this conversation with Zeke Emanuel back in September before the presidential election. Since we spoke, the Biden administration proposed a new plan to have Medicare and Medicaid cover GLP-1 drugs like Ozempic and Manjaro.

As of now, Medicaid coverage varies from state to state, as we just heard. And Medicare doesn't reimburse for these drugs at all because of a law prohibiting the coverage of weight loss products. This proposed new coverage would cost an estimated $35 billion over a decade or $3.5 billion a year.

Which sounds like a lot until you put it up against what Emanuel told us the U.S. spends each year on obesity-related health care, around $175 billion. Right.

It's too early to say what will happen to the Biden administration's GLP-1 proposal under the Trump administration. Trump's pick for director of health and human services, Robert F. Kennedy Jr., has criticized GLP-1s. But Mehmet Oz, Trump's pick to run the Centers for Medicare and Medicaid Services, has expressed support.

I did ask Zeke Emanuel during our interview how big of a shift he would envision in U.S. health care policy if Trump won the election. If I were a betting man having worked with Donald Trump, this isn't going to be a priority of his. He may make another run at repealing the Affordable Care Act, but that's a joke.

It's not going to happen. It's a joke because it's ensconced. It's just not going to happen. Even Republicans in Congress, you know, I talked to him right after John McCain did his thumbs down and killed the repeal. And he said, oh, I'm very close. I'm going to do it again. We're going to get it this time. And I said, Mr. President, what you don't realize is that behind John McCain, if he hadn't done that, there were 10 other senators involved.

who would have rejected it because it would have upset things too much in their state. Every single state that has tried to expand Medicaid where the voters had a say, the voters said expand Medicaid. And we're talking about deep, deep red states, places like Oklahoma, places like South Dakota. Even Republicans want everyone to have health insurance. We're not repealing the Affordable Care Act.

You're well known for your involvement in the Affordable Care Act. You're also well known for having written several books. One of them published, I believe, is 2014, was called Reinventing American Health Care, How the Affordable Care Act Will Improve Our Terribly Complex, Blatantly Unjust, Outrageously Expensive, Grossly Inefficient, Error-Prone System. That's a lot of promise for one subtitle. How well do you think that promise has been met? So far, I think it's been met

reasonably well. Here's how I would put it.

It's dramatically increased coverage. Tens of millions of people have gotten health insurance and gotten the benefits of health insurance, including less mortality, less stress, less anxiety. Secondly, it's actually led to a plateau in health care spending as a percentage of GDP. We were at 17.5% of GDP spent on health care when we started with the Affordable Care Act. And guess what? We're at the exact same place.

That's trillions of dollars of savings. To be fair, that's a larger share of GDP than any other country in the world by a long shot. Don't get me started. We got to have a whole nother conversation about that issue. I could go on and on about it. But yes, we spend, I think Switzerland's the next highest country in terms of spending about 8,000 per person. We're close to 13,000 or maybe even over 13,000 per person. So yes, we're burning lots of money that we shouldn't be burning. In any case, those are two big things.

accomplishments of the Affordable Care Act. It's also by getting more people insured led to some cost savings. On the quality side, I would say much more uneven, not consistently beneficial. And for me, it's been a disappointment. We still have high levels of hypertension, high levels of diabetes.

worsening mental health crises. On the issue of equity, you know, lots of people are concerned about minorities and others not getting as much. The fact is we have narrowed the uninsured rate between minorities and whites. So we've done okay there, I would say. We haven't evened everything out, but I think we've done okay. I'd say the one big place where it's gone awry is the dissatisfaction with the healthcare system is higher.

a lot more barriers and hurdles, more prior authorization, both for patients and doctors. Harder to find doctors for your particular condition. And also, even though we have the same GDP spending, the out-of-pocket spending has gone up. Employers are shifting more costs to individuals through higher deductibles and things like that. That leads to frustration and stress. So I do think the Affordable Care Act has achieved a lot.

But the underlying defects of the system prevent us from achieving all the goals we need to achieve with health care. And how can those goals be achieved? This is a problem in our country. We have to move with the times. We have to be more innovative. That's coming up after the break. I'm Stephen Dubner speaking with Ezekiel Emanuel on Freakonomics Radio. We will be right back.

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Let's talk about the future of medicine generally, but especially I'm curious to know what you think AI and machine learning and so on will do to, you know, accelerate discovery, treatment, et cetera, et cetera. I want to frame this with an observation I heard from Mustafa Suleiman, who's an AI entrepreneur, I guess you'd call him now at Microsoft.

I heard him say that if AI proceeds as he sees it, that the cost of medical diagnosis will eventually drop to zero. Now, let's say he's only 30 percent right. There's a 30 percent cost savings on diagnosis. But that's massive. I'm curious how you think in a world where that's true, how that money gets reallocated.

Well, first of all, Stephen, I was just at a meeting that my brother put on and every panel talked about AI and the promise of AI. And I do think there's a lot of promise there. Don't get me wrong. But I also think that it's going to take longer to make it into the health care system because, first of all, you've got to spread it out over 330 million people, which means not that it's hard to scale AI, but it's going to take a lot of time.

But you have to make sure it doesn't bias you against certain populations or ignore problems in certain populations. And to some extent, the training systems are not good at that. I also think there's some hesitation in using it. I do think the biggest advantage is going to be in access population.

people who can't get to the doctor, that's actually going to turn out to be a huge benefit. I should say conflict of interest. I'm involved in several companies looking at that. There are other huge advantages. One of them is diagnoses, identifying people who are likely to have complications. So you can intervene now and prevent a hospitalization and save money. So I am optimistic over a slightly longer time horizon. If I'm

I were reallocating that 30%. Here's my top priorities. Priority number one, invest in children and as early as possible, even before they're out of the womb, you got to invest in them. We know early interventions produce the biggest social benefit. So right when they're born, have nurse family partnerships so that families are supported and

We have to have daycare that's cheaper so people can afford it. Mandatory, pre-K, open to everyone. I would also bring down the total health care costs for people. One of the major things is we need to put a cap on out-of-pocket expenditures, deductibles, and co-pays so people don't go bankrupt and aren't stressed by the cost. I think a maximum of $1,000 for a family is probably a place I would like to get to, but

You also need to spend that money in other things. It's not just health care. We need to spend it on infrastructure so that we can have housing and people can commute without having to drive hours and hours. So the COVID pandemic taught pretty much everyone how to use Zoom or some equivalent. And this was plainly vital for medicine at the time, what we now call telemed or telehealth. I'm curious what you see now.

as the lasting effects of that telehealth surge during COVID, pros and cons of, let's say, continuing to lean on virtual medicine? I think in general, it's positive. We had a big blip up. Almost half of the physician engagements got to telemedicine, and then it's come way down, not to pre-COVID levels, but way down. A lot of this goes to how we pay for it.

And the fact that when a lot of systems, doctors who do it get paid half as opposed to seeing the patient in their office. But we've also realized that we can do a lot of things out of the hospital. So you're seeing a lot of surgeries migrate out of the hospital. You're seeing more home care available.

out of the hospital. At the University of Pennsylvania, one of the things we ended up doing during COVID was to go to patients' houses and administer chemotherapy. When I was training Lothies many years ago in the early 1990s, if you had told me,

we're going to give this chemotherapy that caused a lot of nausea and vomiting, we're going to give it at the patient's home. I would have said, the psychiatric hospital, that's not far away. Let's take you over there. But that's what we've been able to do. Now, partly that's because we have better drugs for nausea and vomiting. Partially, it's because we really understand how to do this. And that's a big, big advance. Here's why I'm really positive about

about telemedicine. 20% of our population lives in rural areas. We've seen hospitals close there. We're going to have to get them access, not just to a primary care doc, but to specialists that aren't living nearby. And telemedicine is going to be important. Here again is another legacy of history that people don't pay attention to.

Medical licensure and regulation is state-based. That makes no sense in the modern era with Zoom. If you're in South Dakota and you can get your treatment from Chicago or Pennsylvania or New York,

Why should we have the licensure only in South Dakota? We really need to get to the next level national licensure. But, you know, states are jealous of their prerogatives. They're not going to give it up easily. This is a problem in our country. We have to move with the times. We have to be more innovative.

Let me go back to administering chemo at home during COVID, which is really interesting. Let me hear you speak a little bit about how cancer care and especially chemo have changed over the past couple decades. But I want to frame that within a bigger question, or maybe it's just an observation, which is the following. There was an economics paper years ago. I don't know if you ever read it, and I'm curious to know what you think of the idea.

which is that the so-called war on cancer, which was begun, gosh, over 50 years ago now. That's right. Some people claim it's been nowhere near as successful as one might hope. The paper argued that that argument is masking a big different trend, which is cardiovascular care has become so much better that many, many, many people are not dying of the cardiovascular diseases that would have killed them in an earlier generation and are living long enough to get cancer.

I'm curious to know what you think of that framework, but I'd love you to just give us the state of cancer care and especially chemo now. Well, at one time I might have been skeptical. Yes, we began this under Richard Nixon in the early 1970s, and it's now more than 50 years ago.

All of the progress we've made over the last decade or two really go back to the research that was started of the war on cancer and accelerated by the Human Genome Project and figuring out where the defects are in the DNA that lead to cancer, being able now to target those specific defects. All of that took a long time. We've done a marvelous job at cutting cancer death rate.

That means that for everyone who gets cancer, fewer people die. But I do think we've had a huge, huge improvement in cardiac disease. Multiple factors, a lot of lifestyle factors, humongous drop in smoking, changes in diet. So we are more aware of cholesterol, people on statins, incredible breakthrough drug development.

not to mention all the other interventions, stents and things like that. So we have had huge progress in cardiovascular disease. Now, having said all of that, we're seeing a big increase in younger people getting cancers, which we thought they never should get, like colon cancer. I had a very dear friend,

die in her early 40s from a humongous colon cancer. When I was training in the 1990s, we never would have seen that. Never. What do you think's going on? No one knows for sure. Here are some possibilities. We've changed the human microbiome in the gut, the bacteria, by eating the wrong things.

ultra-processed foods, that causes obesity. It also causes a decrease in the variety of bacteria we have and a decrease in the good bacteria. You know, that microenvironment that affects cells created by the bacteria in our gut is probably critically important. If you don't eat fermented foods like yogurt, kimchi, if you don't eat

a lot of fiber that comes with fruits and vegetables, you're dramatically changing that microbiome. That's a hypothesis. Let's be clear with your audience. It's a hypothesis. So, Zeke, I understand you had a birthday recently. Yes, 67 years old. Is that true? Oh, boy. You're spies. You worked for the CIA recently? Yeah.

Can you confirm, though? You're 67 years old. I can confirm I'm 67 years old. I know that every year...

you set for yourself something new, radically new to do. You've become a chocolate maker. You've become a serious cyclist. Tell me one thing that's on your list for the future. I'll tell you a trivial thing. I want to make honey. I thought bees did that. We've just planted a lot of trees. We have a lot of bees that love our lavender plants. So that's a sort of hobby. But I would say seriously, one of my life goals is

I'm a firstborn, and I think one of my deficits, if I had to put it this way, is I can be slightly not sufficiently empathetic. I can be a little too dismissive, and I would like to improve those. I'd like to be more empathetic to the people around me and decrease the sarcasm in my text.

responses. Now, why do you care about that at this stage in life? I think it makes a difference to people. I've become more interested in how people get to where they are and also more interested in what changes they've made, what challenges they've confronted, how they've overcome their challenges. And I'd like to do more of that. My father-in-law makes me

bookmarks, the most recent bookmark for my 67th birthday. He wrote on the bookmark, allergic to idiots. I am allergic to idiots, but I had in the past confused that with not taking an interest in people. And that was probably a result of being first born, having my brothers constantly attack me, you know, whatever. Can I say all of you brothers complain about each other in exactly the same way as if birth order was irrelevant? Yeah.

But I would say being curious about the lives of other people. It's led me to read a lot of biographies and understand the challenges people have overcome. I've read a recent biography of Hubert Humphrey and the kinds of challenges he confronted. But the fact that everyone liked him, that's an interesting and very important quality that you could be open to people. You could be empathetic of people, even people who you disagreed with so much.

that they actually liked you. We don't have enough of that in our society. And so one of the things you ask me, you know, I'm Jewish and the new year is coming up that I'm committing myself to is more empathy and less sarcasm in my voice, but also making honey, making life sweet. The,

The late in life empathist. I love it. Now, I'm sure you get asked about this all the time, and I'm sorry if it's a pain in the neck, but you did publish a piece in The Atlantic back in 2014, which got a lot of attention. Headline was Why I Hope to Die at 75. First of all,

Just rehearse the argument. What was the point you were trying to make? I believe it was a bit misunderstood. Yeah, it's not like I'm going to die at 75. It's that I would not take life prolonging treatments at 75, like cancer chemotherapies or renal dialysis if my kidneys fail. But you also said no more flu shots, for instance. Right. There are two things that have gotten under people's skin. One is vaccinations and the other is antibiotics that would

readily curate condition.

Now, on the vaccines, I think COVID has somewhat changed my attitude on that because, you know, you can get a shot and it would make a very big difference. Why did you need the COVID vaccine to persuade you of that? Wouldn't what you just said describe just about all the vaccines that are commonly used? Well, measles is not my big problem, you know, and diphtheria is not my big problem. Thank you very much, Stephen, if I somehow broke my hip.

I would get that repaired. I'm not forswearing all medical care. It was really about life saving. You know, people, oh, the golden years, all the advertisements out there for Medicare Advantage health plans make the golden years look like I'm hiking in Montana and beautiful vistas and all that. That's not what they're like.

What happens for most people is they end up watching a lot more TV. They tend to be homebound. They get a lot of disabilities over time. They're not filled with the joys that everyone imagines if they're going to get 10 more years.

The other thing is they're also filled with a lot of cognitive decline. Yes, it is true. The rate of Alzheimer's disease has actually gone down, but the total number of people with Alzheimer's gone up. I think the number is, and I haven't checked this recently, by 80 years old, about 30% of people have some cognitive decline. That's a huge number. So you want to get out while the getting's good. I see no reason in prolonging that if I'm not being creative, I'm not interacting with

I don't watch TV, so I wouldn't want to be spending my time watching TV, even good movies. That seems like a very passive life. I'm not a passive person, and I don't think anyone wants or should want to be a passive person. But for all your optimism about intellect and technology generally, whether it's AI, machine learning, or just the way the brain can come up with things,

Who's to say that all the downsides that you see of aging won't be mitigated to some degree by various technologies and that maybe, you know, heck, you could at 100 be

be doing things now? Maybe you'd be doing them quasi virtually, but do you entertain those kind of thoughts? I entertain those thoughts, but I haven't seen that actually be a reality. I think people are delusional when they imagine I'll be like I am now when I'm 90. Probably not.

Maybe AI, regenerative medicine, maybe those things will happen. Then I'll reassess. But they're not happening now. We're seeing greater disabilities and people having a lot of cognitive decline. I am not wild about that kind of life. You have to ask yourself,

what is the purpose of my life? Why am I living? And how does that relate to age? Most people will say, if you just ask them, oh, I want quality over quantity. But then when they actually behave, they are taking quantity, even when the quality of their life is not what they actually want. Of course, I think my view is the right view. I've spent a lot of time thinking about this, but I will tell you, Stephen, it's a decade of people writing to me.

About a third of people say, Dr. Emanuel, you're 100% right. A third of people say, well, you've made me rethink. They don't necessarily endorse my view. If I've just made you rethink how you're going to live your life and examine what you're living for, that's a really good thing. And, you know, a third of people think I'm off my rocker, and maybe I am. It's quite a legacy, though, that you've made so many people rethink something as fundamental as the end of their life. ♪

I don't want to pat myself on the back, but I don't mind being what Socrates called the gadfly. Part of what I do as a professor is challenge people about their views, and I want them to rethink their views. They might embrace their views wholeheartedly. That's fine. As long as it's, as Socrates says, an examined life. As long as you can defend and justify where you've come down. That's the place people need to be. And I hope everyone gets there. I hope they think.

think through, what am I living for? What good am I doing in this world? Whose lives am I making better? In the end, that's why we're here. My thanks to Zeke Emanuel for a conversation that I found informative, challenging, occasionally inspiring. I'm curious to know how you felt.

Let me know. Our email is radio at Freakonomics.com. Coming up next time on the show, another one-on-one conversation. This one with Adam Moss, who is widely considered the best magazine editor of his generation. He also happens to be my former editor and boss. I learned a lot from Adam, especially how to be direct. I just thought this was bullshit. And I thought it was bullshit over...

a long period of time. That's next time on the show. Until then, take care of yourself and if you can, someone else too.

Freakonomics Radio is produced by Stitcher and Renbud Radio. You can find our entire archive on any podcast app, also at Freakonomics.com, where we publish transcripts and show notes. This episode was produced by Zach Lipinski. The Freakonomics Radio Network staff also includes Alina Kullman, Augusta Chapman, Dalvin Abouaji, Eleanor Osborne, Ellen Frankman, Elsa Hernandez, Gabriel Roth, Greg Rippin, and more.

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