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Richard Helppie
This is Rich Helppie, your host of The Common Bridge. We have a returning guest today, Dr David Harlan. Dr Harlan has had a very extensive career with the United States Navy and with prestigious hospitals. He is a specialist in diabetes. Last week, there was a press conference at the White House, and it was announced that there is going to be price supports for two drugs. They’re known as GLP-1 drugs, needed to treat diabetes and obesity. Lots of claims were made during that press conference, like one in three Americans is obese. Not being a clinical person myself, [I look to] my good friend Dave Harlan. I said, Dave, would you be willing to come on The Common Bridge and talk about this? So thanks for jumping on with me today.
Dr. David Harlan
It’s my pleasure, Rich.
Richard Helppie
Dave, for the folks that don’t know you, tell us a little bit about your qualifications and what your current practice is, particularly as it pertains to diabetes and obesity and things that might relate to these new compounds.
Dr. David Harlan
Well, I’ll try to do this in 90 seconds or less. I grew up in the Midwest, in a state south of Michigan that we don’t like to mention.
Richard Helppie
Not during this month we don’t. [Laughter.]
Dr. David Harlan
I knew pretty early that I wanted to be a physician. I went to the University of Michigan, and I was an independent major in a field called physiology, which is the engineering of biology; how systems work. I spent four years at Duke Medical School, stayed on for my residency there, and then I was in the Navy. And while I was in the Navy, it dawned on me that a lot of things that we treat we don’t really understand. We’re just putting band aids on illnesses. I won’t share the whole epiphany story, but I had an epiphany that I wanted to understand diabetes sufficiently well so that we could come up with curative therapies for the disease. That meant going back to Duke, learning how to do molecular biology, transgenic mice - for people who know what that means - and that led me back to the Research Institute in Bethesda, Maryland, Navy, where we developed an immunotherapy that was a big thing for a while. I was on CBS nightly news one night describing our new approach, and the NIH invited me across the street. So for ten years, I was the diabetes branch chief at the National Institutes of Health. The final corner of this story is that when I was at the NIH, I had a second epiphany, and that is we were treating people with complicated diabetes, so I would travel around the country and say, if you have someone with uncontrollable diabetes, send them to us, for their uncontrolled diabetes because we can try experimental protocols for them. We found out that three quarters of the patients referred to us - from the very best places - had what I called controllable diabetes, which set off cognitive dissonance in my brain. How can these be referred from the very best places for uncontrollable diabetes when it’s not uncontrollable at all? And that slowly led me to the conclusion that we have a really terrible healthcare system for chronic diseases; it’s terrible. What people needed was somebody to talk to, and our system doesn’t do that.
Richard Helppie
Is it as simple as what RFK Jr said as a candidate for president, and as he said as Secretary of Health and Human Services? I’m not sure when he said this, but part of his stump speech was, for the price of these drugs we can give everybody organic food and a gym membership. Those are things that would control diabetes.
Dr. David Harlan
Gosh, Rich, going back even... I graduated from Duke Medical School right after they invented dirt. I think you remember when they did that - a long time ago. But I had a professor of medicine there that said, if everybody quit smoking, didn’t gain weight, wore their seat belt, didn’t drink to excess, they’d put medicine out of business. You’re saying, basically, if people lead healthy lives, then we wouldn’t have to do all these complicated things. And that’s very true. The trouble is - especially in our society, where we try not to tell anybody what they can’t do - to the limited degree that our Constitution allows there are things that you can’t do: you can’t murder somebody, you can’t steal. We leave people to their own devices, and I’m afraid it’s just human nature that it’s easier to take a pill than to go out and exercise and watch what you eat.
Richard Helppie
It’s that same medical ethics thing; if you have a lifelong smoker with emphysema, should they be treated? (Dr David Harlan: Exactly.) We’re a compassionate country, and people do get dealt a genetic hand. We know, specifically, that Pacific Islanders, Polynesians, exposed to a Western diet will be rampant with diabetes and hypertension, heart disease, stroke, cancers and gout. I want to try to shed some light on that. If people cleaned up their diets and did a little bit of exercise, would it obviate the need for dramatic drug interventions for most people.
Dr. David Harlan
I believe it would, but that’s not going to happen in anything shorter than 20-30 years. Look, we knew since 1960 that cigarette smoking caused heart attacks and lung cancer, and yet it took 40 years for the number of smokers to come down. It’s just that societal change occurs very slowly.
Richard Helppie
So this GLP-1 class of drugs, what does GLP stand for? How were they developed? Was it targeting obesity and diabetes, or was it like, oh, hey, look what happened?
Dr. David Harlan
It’s a lot of serendipity. And Rich, give me a subtle signal if I’m going into too much detail, like Dave, shut up for a second. [Laughter.] Goes back several decades, we’ve known for decades, that if you raise the blood sugar of a human or an animal, insulin comes out of the pancreas to lower the blood sugar level. So high blood sugar, insulin comes out of the pancreas and lowers the blood sugar. Well, several decades ago, people noticed that if you raised the blood sugar by infusing glucose into a vein, you got a certain amount of insulin out of the pancreas. If you raise the blood sugar exactly the same - but by feeding the sugar - more insulin came out of the pancreas. It was confusing. Why should it matter how you give the glucose as to how much insulin the pancreas makes? And somebody came up with a hypothesis, well, maybe there’s a hormone released by the gut that goes to the pancreas and tells the pancreas, I need you to make a little bit more insulin than just what’s present in the blood sugar. So they ground up the intestines and they found these hormones that are called glucagon-like peptides, GLP. There’s GLP-1 and there’s GLP-2. They found that if they infused GLP-1 into the bloodstream of an animal along with some sugar, the pancreas made more insulin. So that’s what they are. Now, that was 40 years ago that those observations were made. Here’s another bit of serendipity... do you have any questions about what I’ve said so far?
Richard Helppie
No, that’s a great explanation. They were trying to figure out how to deal with blood sugar, blood glucose and diabetes control and balancing the insulin. So here they are now with this class of drugs, GLP-1, GLP-2 and that was 40 years ago. Then what happened next?
Dr. David Harlan
Well, they looked at GLP-1, and unfortunately, if you give it by a shot, the body breaks it down almost immediately. It lasts in the bloodstream for about five minutes. They said, well, that’s not going to be a very good drug then. And this is an example of why basic scientists say, just let me answer questions, I don’t know why I’m doing it, I just want to understand this phenomenon. Because now, 20 years later, scientists were studying the Gila monster. You know what the Gila monster is? (Richard Helppie: Of course, yes.) The Gila monster eats about one to three times a year. One to three times a year.
Richard Helppie
That’s taking intermittent fasting to a completely new level, when you think about it. [Laughter.]
Dr. David Harlan
It’s true. And large snakes in Africa eat even fewer times, they’ll eat once a year. It’s just that they eat a huge meal when they do, like pythons. So anyway, between meals the Gila monster’s gut atrophies, basically saying, why would I have a gut if I’m not eating anything? But if it catches a mouse and starts chewing on it, the saliva secretes a hormone called exendin, and that causes the gut to regrow. So scientists studied exendin and then somebody noticed the Gila Monsters exendin looks an awful lot like human GLP-1. Maybe we could give Gila monster spit to people and it would help their pancreas make more insulin. And lo and behold, that’s basically how the field got started. Exendin, the first GLP-1 receptor agonist, is Gila monster spit that you grow in a test tube. It’s not the actual spit, but it helps the pancreas make more insulin. Those observations were made in the late 90s. So why is it 20 years hence that there’s this explosion of interest? Initially, with any new therapy like the GLP-1 receptor agonists, you worry about side effects and cost and tolerability. Furthermore, it’s hard to take by [inaudible]. Like exendin, you had to inject twice to four times daily, and it just was a pain in the neck. Why do that? But now the scientists and big pharmaceutical companies figured out how you can give it once a week. And with wider use of the drug, initially for type two diabetes, they noticed, my gosh, these people are losing weight, and their appetites are down, and their sugars are much better. And then later than that, by decreasing insulin doses, decreasing weight, decreasing blood pressure, we began to note it’s causing fewer heart attacks and it’s causing fewer strokes. And the more we studied them, the more we were finding very beneficial effects from the drugs. The weight loss is what really complicated things, because now people without diabetes want to take the medicines just because they are so effective at weight reduction.
Richard Helppie
This sounds - in a very scary way - like amphetamines in the 70s, right? They were diet pills and people are going, hey, you know what? I can stay up all day on these things and they’re kind of fun. They were speeding their brains out, when really, we’re not built to do that as human beings. We’re not really meant to intervene, we need to be in harmony it seems. Some of the high sugar content generates uric acid - is my understanding - which raises your blood sugar, which then leads to inflammation, which then explodes into diabetes and cancers and heart attack and stroke. And instead of going back and interrupting the consumption of uric acid, let’s give a pill or a shot. Is it a pill or a shot form?
Dr. David Harlan
You’re putting uric acid at the center of all of it, and I wouldn’t put it there, Rich. But everything else you said, I agree with. 99.9% of the GLP-1 receptor agonists - and that’s their proper name, GLP-1 Rs - are by injection. There are some pills that you can take. They’re kind of a pain in the neck to take, but you can take them by pill, and the drug companies are developing small molecule pills that’ll be easier to take, that will replace these shots within the next few years. That’s coming now. And I agree, too, with you philosophically. I mean, what if we came up with a cure for lung cancer? Should everybody start smoking again because now we can cure lung cancer? I don’t think so. Like you, I think it would be much better for people to lead healthy lives, but good luck getting people to do that.
Richard Helppie
That is a terrific point right there, if we had an instant cure for lung cancer, oh, great, light them up if you’ve got them. Now we’re saying, look, we’ve got this cure for obesity - we want to get into a little bit about that - therefore, go back to your Doritos and your Pop-Tarts and your Coca Cola. Again, I’m a computer guy, right? Garbage in, garbage out, and this is starting to look like that pattern right now. But let’s say a person is on this... I remember reading, four or five years ago, they said we’ve got to treat obesity like anything else in the medical field. And I’m like, oh, here it comes. Here we are four or five years later and we have drugs that they’re trying to push that can arrest obesity. But what happens if people stop taking it? I understand that if you do take it, you will lose weight, but like bariatric surgery and so forth, that once you stop it, it’s coming back. Am I right about that?
Dr. David Harlan
You’re absolutely right. I’ve had countless patients say I hated it when I was obese. I hated it, and now I get how important it is to watch my diet and exercise. But I don’t want to take these medicines anymore, trust me, I’m not going to gain weight. And guess what happens? They stop the medicine and they gain weight. Rich, we were talking about genetic predisposition, most people - and it’s perfectly logical to think this way - view obesity as a willpower problem. You’re just eating too much. You’re exercising too little. But there is another way to look at it, and there are a lot of people who believe it. There’s a strong genetic component to obesity. You take identical twins that are reared apart from birth, and look at their body weight 60 years later, and they’re very close. It’s a very strong genetic thing. Look at it this way. Let’s say you and I - not you and I, because we’re both lean, we’re blessed to be lean - somebody that’s obese and you or I eat a hamburger. The obese person’s fat cells, for reasons that we don’t completely understand, basically suck up those calories very fast and turn it into fat, and then their brain says, well, that may be fine for my fat tissue, but I still need some energy for my brain too. That doesn’t happen with you and me. Our calories are more efficiently distributed.
Richard Helppie
So what you’re saying is everybody’s gut is a little different, (Dr David Harlan: Yes.) and that medical science can’t really look into brains or guts yet, although we are beginning to understand that there is a connection. I can say that A, I’m not that lean, and B, I do watch what I eat because of how my body would react. But that gets us into two other elements of this. One of them is the definition of obesity, which on my BMI, I might be, but I’m certainly not by any measurement of my waist or physical fitness and ability to run and all that kind of good stuff. And then the other one has to do, frankly, with the level of affluence. I watched the presser, I was actually on an airplane, and the press conference, they kept repeating, one in three Americans is obese. One in three Americans are obese. And my data mind went to, uh oh, define obese, because if you can define it low enough, people get on it, don’t get off of it. Then I looked around the first class cabin. There were 20 people in the first class cabin. All of them looked lean and fit. And then I recalled that back in Hurricane Katrina, one morbidly obese woman after another, was being pulled out of the flood waters in one of the poorest places in America. At that time my epiphany was, there’s something wrong with the food supply, and there is. And so there are two big things here that go into this whole equation: the definition of obesity and why is it today that affluent people are lean and low income people are obese. Remember, it used to be, if you were poor, you were emaciated, and the affluent people were fat cats because they ate too much. I don’t even know if we are on topic here anymore, but just observations from a lay perspective.
Dr. David Harlan
They’re fair observations. They’re broad generalizations and you know as well as I do, how those can be misconstrued, but I do have some comments.
Richard Helppie
How long do these things last? I mean, you’re good to go once you start taking them but you stop, and you gain weight again.
Dr. David Harlan
People have taken them now for 20 years, Rich. I was one of the first people to ever prescribe them when I was at the NIH. All the data so far says the safety signal is great, really good, and that the benefits clearly outweigh the risks. But let me say a couple things about what you said. You may want your readers or your listeners to fact check this, but the generalization I’m about to make is basically true. When Pearl Harbor happened and young men went to sign up for the military, I think about a quarter of them couldn’t qualify because of their weight, and it was because they were underweight, not overweight. They weighed too little. Now, fast forward the 80 years since then. Now it’s a third. And you say, how do you measure it? There are really good ways to measure it, but the expedient way is what is the BMI. How tall are you and what’s your weight? By that criteria, Muhammad Ali, in his prime, would have been considered obese. You know he wasn’t obese, he just had [so much muscle.] But for most people, that excess weight is fat and we arbitrarily say anybody with a BMI greater than 30 is obese. If you went back 60 years ago it wasn’t like it is today. It really has changed. Now, what’s changed? That’s the million dollar question. The current way of thinking about it is that... especially in areas like New Orleans, where I was stationed as a public health service officer right after Katrina, I saw that stuff firsthand. They are food deserts, and the cheapest food you can buy is the ultra-processed carbs and stuff that stores forever. They taste good and they’re cheap, and that’s what those people eat. I don’t know what your diet is, but I try to eat things that grow out of the ground, and not so processed foods.
Richard Helppie
So here’s where we are as a country then. We are now creating a new, permanent class of pharmaceutical customer. (Dr David Harlan: Yes.) We are going to meet that price point with the taxpayer dollars. And it’s not only our taxpayer dollars, it’s the children and grandchildren, their dollars. And then over here, our taxpayer dollars are going to nutritional support, but there are no guardrails on the nutritional support, so all of the high sugar content, the high fat content, the ultra-processed stuff, we’re subsidizing that. So in effect, as a country, we’re subsidizing people putting harmful things into their body and then subsidizing a pill or a shot that will help offset some of the damage done by that bad stuff we put in.
Dr. David Harlan
I don’t disagree with anything that you’ve said. There was a study done in Boston by a guy named David Ludwig. Smart guy, good guy, maybe 15 years ago now. All he did, he went into homes where there were morbidly obese adolescents, and he got them to agree that they would no longer have any sweetened sodas or juices in the house. That’s all - just get those out of the house. Promise you won’t bring them in. The adolescents lost something like 15 or 20 kilograms in one year. So yes, we’re poisoning ourselves, there’s no question about it. I think the solution would be, don’t tell people you can’t drink soda, but do something like JFK did in 1960 and have a President’s Council of Physical Fitness, and make it cool to be out exercising and walking around in the cities. Use government funds to build gardens and have healthier food available to people, build up the family unit again and things like that. Those are the better long term solutions for our country and for our species.
Richard Helppie
We had Dr Ken Cooper on The Common Bridge some years back, the father of aerobics, 90 years old, still amazingly fit and strong. And I remember when I asked him if he had any final comment. He said, yeah, everyone should get out and get moving, go walk the dog, even if you don’t have a dog. So now we’re in this political economic dilemma where we are funding pharmaceutical companies to basically get people addicted to a product. Can you think of any policy solutions that we could go upstream with as a people, as a government, and say, look, here is an incentive or a support, and by the way, availability to wipe out the food deserts so that we can get people nutritious food?
Dr. David Harlan
Well, food is very important, but I think exercise and just a healthy living style [is too]. I think whatever we do, it has to align us and incentivize is the way I describe it. One way to incentivize people - I think President Trump proposed something like this the other day - quit giving all the money to the insurance companies who make money by denying care. Give it all to the people and say make your own decisions. You can spend your money to buy food, and it’ll cost you this much, or you can develop problems, and then you’re going to have go on medicines, and it’s going to cost you more.
Richard Helppie
Nate Kaufman and I have been delving into this. The record shows if you give segments of the population - individuals across all segments of the population - money, they go buy a TV, and then they’ll still be on Medicaid and still needing to get treatment. Look, nobody wants to see anybody in this country suffer with a disease. We all get dealt a genetic hand, and all of us are going to have an issue someplace, somehow, with the genetic hand. Like, most people will get lung cancer or some other type of cancer if they continually expose themselves to cigarette smoke - doesn’t mean everybody will, but the vast majority will. Similarly, there are people that can eat highly processed foods and drink a lot of sugary sodas and the like and they’ll be fine. But still, we’re kind of in that same level of statistics — most people don’t get away with it. It’s like playing Russian roulette with five rounds in a six chamber gun.
Dr. David Harlan
I think so. I saw part of your Common Bridge with Nate Kaufman. What about putting the money in a health savings account where it can only be spent on certain things? That would get around some of that but people will still make bad decisions, Rich, they have since we became a species. People make bad decisions.
Richard Helppie
Well, I like the idea of a health savings account, and the technology is out there now, right down to what SKU, stock keeping unit, you can buy with that so there would be a way to control that. And of course, there are ways to go around that, anything that’s got cash value on a street can be abused. But I’m also an optimist, and I think most people, given the choice, given the resources, would make good decisions for their health. Nobody wants to be sick. Most people don’t want to be sick. I think we just need to give them the education, the means, and then get moving, eat better food, stay off of these drug products, because you’re going to be chained to them for life. What do we know about the side effects? Is there lethargy or do people feel great when they’re on them? What do we know about the side effects?
Dr. David Harlan
In general, Rich, when people lose weight there’s another interesting thing. I’ve done some monkey studies before. If you feed a monkey a high carb diet and let it get obese, and then you watch what it does, you’d swear it was a human, except it doesn’t have a remote control for the TV. They just sit there. Well, there’s something about obesity that saps your energy. When people lose weight, lo and behold, they start getting up and they’re more active. So what do I think? I alluded to cigarette smoking. It was 1960 when the surgeon general first came out and said they’re dangerous. That’s an example. But we’ve also, as a society, hated drunk drivers so we’ve advocated seat belts. All these things we know help. And if you look over decades, you begin to get behaviors to change. I would have public service announcement after public service announcement with every athlete, every actor, actress, any influencer, saying lead a healthy life. Do these things that we know help. They’re cheap, and they just make people happier and healthier. And yes, people feel better. The main side effect with GLP-1 receptor agonist is nausea, some constipation, some bloating. This is intriguing to me. Even people with compulsive gambling, those agents do something to the brain. I’ve had patients say it used to be when I’d walk by the refrigerator, I could hear it calling my name. I could barely pull myself away from it. Now I just walk by and I don’t care if there’s food in there or not. Compulsive gamblers will tell you that they don’t feel the compulsion to gamble. Alcoholics, drug addicts will say it’s taking the edge off. It does something to the brain.
Richard Helppie
A lot more study needs to go on and a lot more caution. I like the idea of public service announcements, but also you’re going up against the advertising budgets for the pharmaceutical industry. I mean, you know the jokes, right? I watch them, they’re singing, they’re dancing, they’re traveling to Europe, they’re on a boat. And I’m like, I want that disease, it looks like a lot of fun, whatever they’re up to. The BMI, the joke around it is like, no, my weight is fine, I’m just four inches too short, one of those things. I mean, we have to get to some gross measure with that, until all of the diagnostic tools are available to everybody. We continue to develop things we can, but again, let’s face it, a downside of capitalism is companies like Coca Cola. One of their former CEOs wrote a book, and his view was that everything a person drinks - every liquid - he considered competition. He looked at soup as a competitor to the Coca Cola company. That’s the kind of power that we’re looking at, versus the socially responsible thing of enjoy a Coca Cola from time to time, but it shouldn’t be one every day, and certainly not every week as well. But I don’t know how we get that information out there. Maybe people listen to this show.
Dr. David Harlan
We’ll tell them. I think communication is key. And as the Pogo comic strip said decades ago, “We have met the enemy, and it is us,” we buy stock in Coca Cola because it views every other drink as a competitor and makes money. So somehow there needs to be... in medicine I always say, yes, there’s the profit motive, but then there’s also the profession of it. And it’s true that I could come up with the best treatment for everything, but if it made people lose money, it wouldn’t work. So you need to find a way to do both. People have to make money and do the right thing, and that’s where the friction comes.
Richard Helppie
No margin, no mission. Dr Dave Harlan, I appreciate you spending the time here. What didn’t we cover about these new drugs? Any closing comments for the listeners, readers, viewers of The Common Bridge? If they came to your office today, either as a fit, lean person or a person with morbid obesity, what would you want them to know?
Dr. David Harlan
I would conclude with where I started, what I learned in medical school 50 years ago, that if you lead a healthy lifestyle, you will reap benefits more than anything else that we do. Don’t smoke, stay active, stay lean, don’t drink to excess. Wear a seat belt. Get the vaccines that have been demonstrated to be safe. But if you’re one of these people that is really, really just crushed by obesity and its complications, these medicines are safe and effective, very effective unlike anything we’ve ever seen before. Let’s hope that something better comes along in the next years and decades. Those are my final comments, I always appreciate the opportunity to talk to you, Rich, you know that.
Richard Helppie
I love the fact that we’re staying on brand for The Common Bridge, which is to inform versus influence. I believe we have a very intelligent audience that does want to sort things out for themselves, and if we can provide good sources, we’re going to do that. With our guest today, Dr David Harlan, this is your host, Rich Helppie, signing off on The Common Bridge.
