What REALLY Happens When You STOP Taking Insulin for Diabetes?

Yeah, there's. There's a lot of sort of societal debate, like how do we get insulin price lower and lower and lower. And I always say, guess what's better than a lower insulin price? It's eliminating the need for insulin in type 2 diabetes context. Obviously, type 1 is a different disease.

So. Welcome, Samy, and welcome, Dr. Shadia Grishma. It's so great to have you on the Doctor's Pharmacy podcast. The topic we're going to dive into today is one that is, I think, existential for humanity, which is this crisis of metabolic dysfunction that affects a huge swath of the population, especially in America, where 1 in 2Americans is pre diabetic or has type 2 diabetes. 90% don't even know it. We have 93% of Americans who are metabolically unhealthy, meaning they're already starting on that trajectory. And it's driving so many of the costs, according to healthcare system, is driving so many of the chronic diseases, like not just diabetes, but Alzheimer's, cancer, heart disease, mental health issues, all driven by metabolic dysfunction. And in medical school, it was something that I really never learned much about. And Grishma, I'm sure you didn't either. And we really sort of struggle to treat this problem, which seems to be getting worse and worse and worse. We're getting more and more medication, more and more drugs, more and more treatments, but. But the problem keeps getting worse. And what you have done in this extraordinary company, Virta Health, which we'll dive into, is to find a way through the mess of medicine to the root cause of why we're having this metabolic dysfunction and help reverse it. Now, when I went to medical school, I don't know, Reshma, if you went to medical school, this was the party line. But the party line was if you get type 2 diabetes, it's a progressive disease that is not reversible. But this is actually not true. And for those people listening with type 2 diabetes, and make sure you understand, I'm not talking about type one, which is an autoimmune disease. That's very different. It's not easily reversible. But type 2 diabetes, based on the science and a lot of the work that you've done at Virta Health and the science you published actually is reversible. And it's not something that you hear when you go to the doctor's office, if you go see your physician and you have type 2 diabetes, they're not going to tell you this is a reversible condition. They'll say, I'll help you manage it. I'll give you medications you want, maybe want to improve your diet and lifestyle, but you've got to accept that this is a lifelong, progressive, irreversible condition. Can you explain, you know, first start with Sammy, how you kind of got into this field because you're kind of an unusual character that was an entrepreneur, but an athlete, and you kind of discovered that what you were doing to fuel your athletic performance was not really getting you the health that you wanted. And then we'll sort of go into sort of really answering the underlying issue is, you know, why do we have this epidemic? Why are we failing at treating it? And why is there actually a new approach that may be the answer to solving so much of our extreme metabolic crisis that we're having today?

Yeah. Well, first of all, Mark, thank you so much for having us here. And I feel not completely adequate to answer the question because I'm the only non MD on this call. So Dr. Shetty, Chrisma here and you. But let me try. Well, first I would say, well, mostly.

It'S also for your experience too. Like, I want to hear, like, how do you get into this stuff?

Yeah. So, and I wanted to say that just to kind of contrast that I actually, I do come outside of healthcare, so I'm a physicist by training, started my career in a nuclear power plant. So that's my only claim to fame for science, for scientific thinking, but indeed I was outside of health care. And the very dire picture that you so eloquently painted, Mark, about the massive numbers of type 2 diabetes and obesity and metabolic disease, effectively, you know, 10 to 20% of people minority in America, adults are what you might call metabolically healthy. So almost everyone is metabolically unhealthy. So, so the diet picture that you painted, that's kind of how I saw the world as well. If you had come to me about a decade ago, and if you had come to me and say, hey, let's go and solve diabetes and obesity, this is solvable. Again, about 10 years ago, I would have rolled my eyes and laughed you out of the room.

That's right.

I literally would have rolled my eyes and left you out of the room. And the reason is, you know, I was a pretty high performing endurance athlete. And while I was building my previous company, which was a tech company called Trulia, you know, I did a lot of triathlons and even got to a point where I won the world championships in triathlon in my age group. And I always thought, well, I am, you know, I'm a healthy guy. I don't have to worry about the things that people in the middle of America have to worry about. And let's face it, blame yourself. You eat too much, you can control what you eat. And if you eat too much, probably develop type 2 diabetes and obesity. So how do you solve that? You bottle willpower. Like, I can't help with that. So this was my thinking, and I'm embarrassed, I'm honestly truly embarrassed to say this. This was my thinking more than a decade.

Well, you shouldn't be because it's basically the thinking of almost everybody, including most physicians and nutritionists in the healthcare system. So you're not alone there, Sammy.

Exact. So finally, like, you know, how did I become a co founder and now CEO of Virta Health here now, almost a decade later? Well, it turns out despite my, you know, winning and running triathlons and staying lean, I discovered that I was on my way to type 2 diabetes myself. And I already had pre diabetes. And so this was around 2011. And I honestly, I was pissed. I was surprised, pissed and frustrated. I said, what the heck? I'm not one of those people. Like, I'm not one of those people. What's going on with you're winning triathlon.

And you're pre diabetic. Right. How did that happen?

Yeah, and I should say fortunately, you know, I got very curious. I was like, what the heck's going on here? And I got lucky that through reading and reaching out to a lot of people, I met a number of scientists, but particularly Dr. Steven Phinney and Dr. Jeff Volek, who had done research over, you know, three decades about metabolism and how the body metabol metabolizes carbohydrates and fat and so forth, and met these gentlemen scientists and basically learned two things and very briefly, one, I was obviously completely wrong. Diabetes and obesity, it's a metabolic disease. It's not a personal choice that you wake up one Monday and say, hey, I'm just going to eat too much to develop type 2 diabetes. So that was one, I was wrong. And then the second thing was kind of what you mark said earlier, which is that these conditions, despite the conventional wisdom, are reversible nutritionally. Yeah, type 2 diabetes, obesity are systematically reversible nutritionally if you know how to manipulate nutrition. And I became convinced, both through personal experience and reading all this published research, that it indeed is possible. And so I'm not going to go too much longer. But this was 2014 and I said, hey, this is incredible. If you can use nutrition in that way maybe I can help with my tech and entrepreneurial background and figure out a care delivery mechanism how we can get this into the hands of millions and millions of people. And yeah, we started Virta Health now it's almost 10 years ago and we had this a little bit of a crazy mission. Reverse type 2 diabetes and obesity in 1 billion people. Reverse type 2 diabetes and obesity In 1 billion people. And yeah, here we are 10 years later and we can go into details, how's it going? But yeah, that's how I became an accidental healthcare entrepreneur. And honestly, it's been the most rewarding journey in my professional career so far.

Yeah, it's kind of a miracle when you as a doctor, when you see things that you were taught were not possible. So you know, Grishma, you're a board certified endocrinologist, you directed the fellowship in diabetes, the Joslin Diabetes center, which is iconic Harvard diabetes treatment facility. It actually started out with Dr. Joslin, who was the preeminent physician in diabetes care at the turn of the last century in the teens and twenties. And, and the treatments they had back then were just very little except nutrition, sort of modifying what people ate and changing their diets. And back then before they had insulin, they used a ketogenic diet as one of the treatments for type 2 diabetes or type, even type 1 diabetes, which was killing people. And it was very effective and it kept these people alive. It was not perfect, but it was really quite an interesting origin story. And now the American Diabetes association doesn't quite recognize that diabetes is a carbohydrate excess problem. It's a carbohydrate intolerance problem. And they're recommending all sorts of things that actually don't, I think, reflect the latest scientific understanding of how the body becomes pre diabetic and type pre diabetic. And so can you share with us your kind of awakening going from a sort of a traditionally trained endocrinologist working at Harvard, leading the training of other leading physicians in this space, to kind of almost come back to the origin story of the Joslin Diabetes center, which is to use a diet as the mainstay therapy for diabetes rather than a whole cocktail of drugs which can cost huge amounts of money every year?

You know, it's funny that it is full circle that our knowledge, what we were doing before we had a therapeutic and you know, insulin was an incredible discovery and saved the lives of many, many people with type 1 diabetes and poorly controlled type 2 diabete. But I think somewhere along the line we lost the sort of nutritional component of controlling metabolic health and it was just easier to write a prescription. And, you know, we live in an obesogenic world now with toxic food, environment, inadequate sleep, inadequate activity, and even with the way we deliver care, you know, patients are frustrated. They don't have enough time with their clinicians, they're paying more, they're having worse outcomes. And frankly, clinicians are also frustrated. You know, they're on the hamster wheel of, you know, metrics that aren't around quality. But you know, how many widgets are patients you see in an hour, which are called RVUs. So the specialties that deal with prevention and metabolic health are not valued appropriately. So I mean, the whole system sets it up for high cost, poor outcomes. And so part of the reason why I was super excited when I found Virta and is one, the nutritional intervention really does flip that mantra of continuous progressive chronic disease of type 2 diabetes like a one way trolley track, right? Like you add metformin when you start, then by 2 to 3 years you add a second agent and by 8 to 10 years everyone's on insulin. So we flip that at Virta and we have great data from our IUH trials that we can sustain remission and weight loss and deprescription of medications over two years. I see this every day in my practice at Virta. The second piece is the model of delivery, the care model we have at Virta. So in my old practice, which is a traditional brick and mortar clinic, I was there for after finishing fellowship, I was there for about 12 years. And you know, my patients, they were lucky if they could even see me every six months because my panel was full. So talk about access. They come in, then they're rushed through that appointment because you've only got 30 minutes to download their glucometer, their CGM, update, their med list, you know, get the labs, the pre check labs, and then they get to the room with you and you've literally got 15 minutes to solve all their metabolic health issues. Like that's unrealistic. So the way we do it at Virta is we've got this continuous remote platform where patients are able to log their biomarkers so their glucose, their weight, their ketones, their blood pressure. And so there's this ability. Our algorithm will generate what we call an attention score, which gets the right signal to noise. So that sweet spot of where the clinician can actually swoop in and take care of the patients who need help. So that is if they're doing badly and we need to intervene more in nutrition or meds or if they're actually really moving in the right direction because they're doing the things you're helping them, coaching them towards, you can reinforce that virtuous cycle by deprescribing medications and move it forward. And the third piece I just want to add because I don't think it's just pharmacology and technology. There's a strong component of the human touch. So we have a patient centric way of giving care. We have a team of coaches and a team of clinicians. And these people are so passionate about metabolic health. And I will say, when my patients start at Virta, especially early on when they're making nutritional changes, they will interact with their coaches multiple times in a day and often their clinicians, their metabolic clinicians, probably daily because we're deprescribing medications, answering questions, keeping them safe. So it's a very white glove, high touch experience for our patients. So I think those are the three things that really drives the results we have. And just to make it really real, like today's Monday. So I did a bunch of lab reviews that came in over the weekend, which I've never, I never thought I would say this, but my lab reviews are actually kind of very joyous at Virta. So this morning I'll just say Mr. W, he's a gentleman from Mississippi. He's been with us for 900 days. His weight is down 80 pounds. He came to us with an A1C at 9. It's now 5.2. He's off three medication, diabetes medications, one including insulin. His sleep apnea is resolved. He's off his cpap. He's only on one anti hypertensive medication. And he's just so much healthier and so happy. I'll just give you one other patient. It's another gentleman from Texas. He's South Asian, 45. He's only been with us for 160 days. He's dropped 17 pounds and his A1C has gone from 8.8 to 7.5. And he's only on one metformin. Now, like, this is incredible and this is not unusual.

And these are changes you just don't actually even see with medication. Like, you just, you can't achieve those results using drugs unless you use massive dose of insulin, which are problematic.

But by the way, I'll add here, I think Chrisma mentioned the IUH trial. So Indiana University Health and Data, which is that when we started Virta, obviously we used telemedicine and nutrition to achieve these results. And when you use telemedicine and nutrition, you don't need FDA approval. It's not a new molecule that we are developing a new drug. But we made this, what at the time this was 2015 seemed like a crazy risky bet. That is, we started a five year prospective clinical trial with practically no funding for the company. And most of my investors were sort of from the tech world and they were rolling their eyes and saying, are you crazy? You're going to spend five years doing a clinical trial? Now, with hindsight, it is one of the best things that we've ever done and obviously we keep publishing data and we have other trials in the works. But the reason it has been a, was such a good move at the time is one, obviously we've attracted people like Griezma to join the company who say, hey, I want to know if this actually works, is this safe, what's the sustainability? And I don't want to hear white papers and marketing materials and be it like, show me the hard data, is it peer reviewed and I can go through. So that's kind of the one reason. But then the second reason is, which I didn't appreciate coming from outside of healthcare paradigms, even.

In light of new data changed very slowly, very, very slowly. Like you, Mark Menzies. Oh, diabetes is reversible. Well, guess what, if we go and poll thousand average or random providers, you know, Harvard trained, Stanford trained, you name it, I don't know what percentage would still say, yeah, no, no, type 2 diabetes, it's, it's chronic progressive, you can't reverse it. So even in light of data, it's honestly, it has taken and still have to work very hard to change the conventional wisdom that many of these, most of the metabolic diseases are reversible and using our data, that's the language of most scientists and clinicians. But even with the data, you know, it's hard work.

Don't confuse me with the facts. My mind's made up.

Right, Exactly.

Yeah. Well, you know, it's interesting when I'm listening to you, Grishma, the two things that I'm really hearing is you're using a different drug and a different delivery system and you're finding the right medicine and the right way to give that medicine to the patient. Because in traditional medicine we do what we do not because it's the best way to do things. Right. We know that lifestyle and diet work better. We know that we can actually have those be effective and yet we don't have a system that actually allows us to deploy that effectively. And so the drug here is a very specific diet. It's not just a healthy diet or a whole foods diet or a Mediterranean diet. It's a very specific therapeutication of food. Is medicine then it's not all the same. What is the drug, what is the dose, what is the frequency, how is it, how is it prescribed? That really matters. And the second piece is the delivery system that the episodic care you're talking about, where you go see the doctor every six months for eight minutes and don't have real feedback about what's going on except being able to prescribe more medication and order a few lab tests. And it's not, it's not the, the right delivery mechanism. So in other words, if you're taking Ozempic, you can't just swallow it, you've got to inject it.

Right?

If you want to actually change people's lifestyle, you can't have an appointment every six months. And so this continuous care model, which is high touch, which is digital, has allowed you to actually deploy this model in a way that's been more effective. And more people are adhering to more than you can ever imagine. Because the problem with lifestyle changes, people just don't sustain it. They might do it for a week or a month or three months, but then they fall back. So can you tell us more one about the actual drug that you're using, in other words, the medicine you're using, the food that you're using to achieve these incredible results. And I think just to sort of talk about the data that I know you can correct me if I'm wrong, But in about 60% of the cases of the people you serve, you reverse the type 2 diabetes, put in remission, you get almost all the people off of the main medications and most off insulin or dramatically reducing their insulin. You see dramatic weight loss, which is far more than you see from most other interventions like 12% body weight, which is a lot. And you see there's this incredible data of improvement in cardiovascular biomarkers which you think would make sense if eating a ketogenic or high fat diet. So can you talk about how this medicine works, why it's effective, why our old paradigm doesn't work? Why with the ADA and why with your average doctor saying an endocrinologist thing is actually not the right approach to treating type 2 diabetes?

Maybe I'll tell Charisma first give the non MD non medical doctor view. Now that I've observed 100,000 plus patients and 10 year journey. And maybe the listeners who are less clinically minded can, can get a few data points there and then I'll hand it over to you. Well, first, Mark, indeed, the results that we deliver, I sort of jokingly, although this holds true these days, say that Virta nutritionally delivers ozempic like results without the drug. Like those are the outcomes that we deliver. And as you mentioned, 12% average body weight loss and not just for six months. 12% at one year, sustained at two years and we'd follow patients out to five years. So the results are very strong. And as you mentioned, in type 2 diabetes context, insulin is usually thought as sort of the last hope drug, hypoglycemic agent for type 2 diabetes. While at two years, from start to two years, 80% of all insulin inverter care is eliminated, which again is kind of unheard of because usually the dose goes up 10, 12% year over year. So the reason 80% of people get.

Off insulin, that's remarkable.

It's, it's, this is 80% of the total dose at start is eliminated on a population level, which is insane. And I think the percentage of people who are completely off is somewhere in the same ballpark. I actually don't remember that number on top of my head, but it is, it's very high. And as you said, 60%, what we call diabetes reversal rate at one year, which does mean that you are completely off of diabetes specific medications and your blood sugar is in a normal range. And yeah, there's a lot of sort of societal debate like how do we get insulin price lower and lower and lower. And I always say, guess what's better than a lower insulin price? It's eliminating the need for insulin in type 2 diabetes context. Obviously type 1 is a different disease. But back to the treatment. So I'll give you the layman's version first. Well, first I should say nutrition is freaking hard. It is freaking hard. Obviously we've had diet and exercise programs for the last three, four decades and practically all of them have failed to deliver sustained results. And sometimes I say, you know, my background in physics, that getting nutrition right is harder or can be harder than nuclear physics or at least in light of the last three, four decade. But here's the couple of cornerstones. Why Virta works. So number one, you have to be able to use nutrition to eliminate unnecessary hunger and cravings. So eliminate unnecessary hunger and cravings. Because if the nutrition program is based on sort of willpower and hunger, willpower always runs out, usually Latest at the wedding photo.

It runs out. And so that's one cornerstone of what Virta does when we use nutrition. We help our patients or counsel them to eat to satiety and as much sort of real food as possible.

That means eat until you're possible. Like, don't calorie restrict.

Because exactly.

What most physicians say is in order to lose weight, you have to restrict your calories and you have to eat less and exercise more. What you're saying is something different here.

Exactly. And obviously, mathematically, that can hold. But again, if it's a mathematical exercise, when the willpower runs out, which it does again at the wedding photo or whatever the milestone is, then weight regains. So that's on a nutritional side. And I'll say one more thing around nutrition, which is we have to. And this is what we do. We individualize more or less to the N equals one. And I'll give you a silly example, but often this is lost in translation in diet programs. So if you're a vegetarian coming to Virta by identity or religion or that, that is your thing, and we tell you to eat bacon and extra breakfast, guess what? We lose you immediately. Also, the other way around, like, we work with one large Fortune 500 company. We work with US Foods. There's a lot of truck drivers, and these are mostly men. And so they're used to, like, burgers and meat and stuff. If we tell them, and obviously this is stereotypical, but if we tell them, okay, it's steamed spinach for the rest of your life, guess what? Again, we lose you immediately. So we have to do a lot of individualization. And so that's on the nutrition side. And Chrisman can go into more details, but those are some of the cornerstones. And then on a care delivery, I'll just mention that, as you said, Mark, you know, even with the best protocol, best nutrition, best nutrition science, if it's, here's what to do, see you in three months, guess what. It's like telling to a driver on a car, okay, just hold on to your steering wheel and keep going. Guess what. First corner, and you're gonna drive to the forest off the road. So it's the same thing with nutrition. So the care delivery model that we have, it's basically daily monitoring, daily interaction. So when you hit the first corner, which could be, I don't know, kid's birthday party, or maybe there's like a death in family or you lose a job, something emotionally really hard to overcome, we are there to help you and guide you and so that wasn't possible without telemedicine. And now obviously with telemedicine, it's, you know, chronic diseases 24. 7 care better be and support better be 24, 7 too. So, so that's kind of a little bit of, on a high level, the nutrition piece and then combining with this 24, 7, more or less 24, 7 support that we can deliver, that has allowed us to deliver those results. But maybe, Griezmann, you can add a little bit nuance to the kind of nutrition piece and how that's different from.

Neil, let's dive into the sort of diet part because I think this is really an interesting conversation because it's not something that most people understand how this is kind of a carbohydrate intolerant disease. When you have diabetes, you become carbohydrate intolerant. It doesn't mean all of us are born that way, but become that way because we live in a sort of a soup of sugar and starch that's washing over us for decades and that leads to the development of this metabolic dysfunction. And the solution is to kind of reverse that trend by restricting carbohydrates and increasing fats and tell us sort of how that works and why we kind of got so far away from it because it was the treatment 100 years ago, and now we're coming back to it as the treatment and explain the biology behind the science of, of ketogenic diets as a diabetes reversal treatment.

So, you know, for, in the trial, our patients were on a well formulated ketogenic diet, which is very low carbs, so 30 grams. But practically in our clinical workflows, we do a lot of low carb. And not everybody's in well formulated ketogenic diet. So we really try to sort of meet patients where they need to be. And there's a lot of heterogeneity in type 2 diabetes, right. We've, in genome wide association studies, we now know there's hundreds of different types of type 2 diabetes. But sort of like the end result or the goal is to preserve beta cell functional mass. Right? And the beta cells are those cells that make insulin. And so anything we can do to de. Stress that beta cell and keep its insulin production up is critical. And when we eat high carb diets, we add to cytokine release, inflammation, glucotoxicity, all of these things stress out the beta cell. And so that sort of accelerates the destruction of beta cell function and mass over time. And that's when you start seeing the one way trolley for type 2 diabetes. So if you can reset that and change that pathway, you can definitely improve insulin secretion and also decrease, while you're losing weight, decrease the insulin resistance at other target organs like in your live liver and your muscles. So you, you also spare the beta cell from having to produce more insulin to do the same job. So multiple layers of de stressing the beta cell through the nutritional intervention directly, but also indirectly by affecting other parts of metabolism. I mean, energy homeostasis is so complex. I have so much humility. You know, I started my fellowship training studying adipokines. I was in a lab where I was studying leptin and adiponectin. And like there are so many other cascades and they all interact with the gut, the microbiome, the brain, your satiety centers, your pancreas. So there's so much complexity. So really thinking about it simplistically though, is really preserving and de stressing that beta cell.

And the way you do that is by basically restricting carbohydrates and adding a lot of fat. Now, it's not the bacon and, you know, kind of cheeseburger diet, right? There's a healthy way to do this. It doesn't mean you have to be eating a lot of food that may not be great for you. And so I think people are often thinking, oh, fat is bad, fat makes me fat. If we eat fat, you get fat. And there's this whole mythology we had about that. And in fact, that was sort of the prevailing theory for so long, and now it's shifted. And we understand that actually for these metabolically dysfunctional people, which is most of America, that we're eating way too many refined starches and sugars. I mean, carbohydrates are also vegetables, so there's no harm in eating vegetables. But the starch and sugar and the refined carbohydrates are the ones that are driving this problem. And so the solution is restricting those. And you're saying you don't always have to be fully ketogenic, you can be very low carb. And I've seen this too. I mean, I had a patient at Cleveland Clinic who was type 2 diabetic on insulin for 10 years, you know, had heart failure, had kidneys starting to fail, fatty liver hypertension, had multiple stents put in for cardiac disease, and was on, you know, 20,000 of coping medications. Her body mass index was 43, which is huge person. And her A1C blood sugar average was 11.2. And we just didn't put on a keto diet, but since she took her off, you know, grains and beans, sugar, processed food, put her on lots of good fats, olive oil, avocado, some nuts and seeds, healthy protein, lots of veggies, fiber, and it was about 50% fat, not 75 or 85% fat, which is what most ketogenic diets are. And within three days she was offer insulin. In three months she was offered medications. Her A1C went from 11.2 to 5.5, which is normal. Her ejection fracture went to normal. Her kidneys got better, fatty liver got better, her blood pressure got better. In a year she lost like 116 pounds. So without Ozempic, without a gastric bypass, simply by getting the group support, which we did and by using kind of a very, kind of low carbohydrate diet that was a very anti inflammatory diet. So what I'm hearing you say is it doesn't have to be always ketogenic, but it has to sort of be matched to that person's state of metabolic dysfunction. The more sick you are, the probably the higher dose of drug you need in a sense. Right.

I would also add that we haven't published this actually we published some, but we actually have very interesting dose response data. So pharmaceutical companies usually do a, what they have to do like a dose response study. So here's the molecule, you add more of that molecule and then see what happens in terms of safety and in terms of outcomes. Obviously you can then tease out the correlation and correlation like oh, more of this acetaminophen. Unless you have pain and whatnot. We actually have very interesting dose response data to carbohydrate restriction and seeing what happens to weight, glycemic control and getting, getting off the meds. And.

I guess the punchline is the, the more insulin resistant you are, the more of that dose the better. Is basically without sharing all of our secrets, but it's fascinating because we've, we literally have dose response curves and, and it kind of tells, tells the story. The other thing I wanted to add, Mark, when I listened to you and I was thinking those patient outcomes and what you had seen, if I wasn't, if I did not have the 10 year history of building virta and seeing exactly the same Results now with 100,000 plus Americans, I would still be like, oh, I'm sure nutrition can work, but come on, these are the grandfather who was 100 pounds overweight and then ran a marathon. We always hear these stories like oh, it's One anomaly, one out of million. But I think really what the world needs to hear this is individuals, business decision makers, policy decision makers, scientists, is that these results are systematically possible. Absolutely systematically possible. And this idea that we have 200 million sick American adults metabolically unhealthy, and the best we can do is manage symptoms with medications is ridiculous. It is so ridiculous. And so we really have to get the message across that there is a way nutritionally, you don't have to be a superman or superwoman, ordinary person. There's a systematic way to achieve those results. Obviously, there's a distribution. Some are hugely successful in terms of moderately successful, but that message hasn't broken through yet. And it has to. And that's why I'm grateful to be on this podcast, too, because it's ridiculous. There's no other way out of this metabolic health mess. GLB wants in. Tap water is not going to solve this mess.

No, no. And it's interesting when you're talking about how you. You. You're.

Sort of able to execute on things in the sense that you learned in your research around these hormones and molecules that regulate appetite, like adiponectin and leptin and the inflammatory molecules that are produced by your fat cells. And that was sort of where your research was. And what we're learning is that the application of the right nutritional approach in metabolic dysfunction actually automatically regulates those hormones. Rather than having to take Ozempic, which artificially does this. Your body can naturally change the levels of the appetite and fullness hormones that are driving this overeating behavior that is driven by the carbohydrates. So when you eat more sugar and starch, you want more sugar and starch. When you eat fat, I mean, I would say Nobody can eat 12 avocados, but anybody can eat a whole bag of Chips Ahoy cookies. Right. So it's just like no limit on that. And I think the body has this natural ability. When you feed it in a way that it's designed to work, it actually resets. And it's not willpower, it's just science. So can you explain how that works?

Yeah.

So when folks increase their fat intake, and certainly when people achieve nutritional ketosis with higher ketone levels, the hormones that drive appetite are naturally suppressed and the hormones that signal satiety go up. So endogenous GLP1 CCK go up and then, you know, things like ghrelin go down. So again, so exactly. Like harnessing nutrition to appropriately do that positive feed loop, that's towards improving health and Decreasing hunger. It drives with just the nutritional changes.

So what's interesting is that, is that you said something that I want to sort of highlight and double click on, which is that when you eat in the right way, you naturally increase your GLP1 peptides which are regulating your appetite and that you don't have to take Ozempic. And what you also said, Sammy, earlier, was that you're achieving Ozempic like results without taking the drug, without all the side effects and without all the costs. And so can you kind of explain.

And we talked about this when we were hanging out in person in Aspen, the data that shows that out there, the pharmaceutical companies are funding billions of dollars of research on these GLP1 agonists and other related peptides around a whole spectrum of diseases from depression to autoimmune disease, to neurodegenerative diseases, to longevity, to obviously weight loss and diabetes, to cardiovascular disease. And they're trying to get all these studies done to get indications for these other applications of these drugs. But what you're saying when I heard you say was that using this nutritional approach you can actually achieve all the same types of outcomes and it's not the drug itself, it's actually the change in your metabolic health. Can you explain more about that, Mimi Grishma and how that works?

Yeah, absolutely. And first upfront I want to say that this may sound like, oh, this guy is so anti pharmaceutical. No, I'm a physicist by training. I believe in science, I believe in western medicine and also these GLP1 drugs, you know, first one was I think in America approved for treating type 2 diabetes 2005. And it's a tool in a toolkit. It is a tool in a toolkit for type 2 diabetes and in some cases for obesity. So I just want to be very clear and obviously virta our providers practice evidence based medicine. So anything I say next isn't going to be like, oh, you know, drugs are bad in all cases. No, that is not the case. But to answer your question specifically, and this is all data that's published in peer review. So if anyone wants to sort of double check, you can go to vertahealth.com and/research and find out published in peer reviewed results. But indeed. So what we've been able to show is that as we run our nutrition program among our patients, the following things either improve or get reversed. Obviously type 2 diabetes, so that's glycemic control. So blood sugar comes down, hypertension, so blood pressure comes down, inflammation comes down. So this is crp C reactive protein, a white blood cell count. And we also have an unpublished paper looking at 16 inflammation protein proteins of which almost all improve, which is unheard of. Better than Humira. That's unpublished. So that's a caveat. Depressive symptoms improve, sleep apnea improves, so gets reversed. Knee pain goes down, cardiovascular disease risk markers and 12 year cardiovascular risk goes down. Kidney and liver function improve. So we looked at EGFR and we can't really say that we can. It would be a little bit overreaching to say we reverse kidney disease but we have shown that we improve kidney function and same with liver function. So when you look at these broad spectrum metabolic health improvements, it's basically the same list that the GLP1 manufacturers are now showing that we either improve or reverse. And we've already published this data. So what can we conclude include again I'm not the medical doctor here, so maybe charisma can kind of COVID me up here. But basically what we, we can show is it is possible to achieve the same broad metabolic health improvements as TLP1's may or may not nutritionally 100 nutritionally. Therefore it is not the exogenous molecule that is achieving these results alone because it's possible to achieve the same results nutritionally. Now we can still debate the mechanism. Is it all about the weight loss or are there other things in play? And our hypothesis is there are other things in play, but again such as information, reduce information. But we can achieve the same things nutritionally, which I think again is a very important message to be heard because in the next year and two there's going to be headlines. Oh, GLB one is now improved. The eighth new thing. The answer is, guess what? Nutrition improves all those things. And then finally I will say again, there's a place for these drugs. GLP1s a tool in a toolkit. But I think this statement holds true, which is we don't know the short, the midterm and the long term side effects of exogenous drugs but we know the side effects of healthy food. Guess what? There are better, longer life.

That's right.

Like healthy food. It's tough to say like what's bad about that. Not much. That's right.

Yeah. No, I think, I think you're right. I think and I'd love to hear your perspective as anocrinologist squishma about the GLP1s and you know, their utility but also the risks and I sort of whether or not they're really necessary if we actually got our nutrition right and we got the delivery system right, which is this continuous care model to support people in behavior change because that's the biggest thing. And you know, I sort of, this sort of conversation you just were mentioning, Sammy, reminded me of a study I read that looked at gastric bypass and they did a controlled study where they took a group of obese patients. Half of them got bypass and half of them didn't. But the diet that the bypass patients got after their surgery was the same diet that the non bypass patients got and they both reversed their diabetes within a couple of weeks. It wasn't the diet, it wasn't the surgery, it was the food. And I hear you saying the same thing about the GLP1. So I'd love Bhishmani to share from an endocrinologist perspective, you know, what, what your thinking is about this, you know, you know, where they play a role and actually is this approach of, you know, very aggressive nutritional intervention with the continuous care model of lifestyle support and behavioral change, you know, actually better. And how do we think about that?

Yeah, no, I think that's a great question. And it kind of hits on something we spoke about earlier during this call with insulin and how we sort of, I think we missed an opportunity of marrying some of the nutritional sciences to patients who were able to receive insulin. And when you think of like even type 1 diabetes, of course insulin was life saving, but because we didn't really invest in figuring out the right nutritional. Now we have a lot of folks with type 1 diabetes who we say they have double diabetes.

Yes.

Which is type one with insulin resistance. Because we've, we've just let people eat whatever they want even if it doesn't work for their body. So I like that, like to think of that as an analogy for GLP1s. You just can't what, eat whatever you want just because there's a new medication. Because guess what? Again, the energy homeostasis is super complex. There's no silver bullet like you actually have to eat right for your body. And there's so many, like I said, the genome wide studies have shown that there's a lot of different types of type 2 diabetes. And the, if we can get to the root cause, we can help a lot of folks and not look at one target molecule that we're using today, which is, you know, the GLP1 therapy and that. So I think really thinking more holistically about our patients that these are not magic bullets. Look, they're great medications for patients with diabetes and other non glycemic Indications like reasons outside of blood sugar control, such as heart disease, heart failure, kidney disease. There's, there's mortality and there's outcomes data to support their use. But what about like the millions of people who have not yet developed those complications, who have diabetes and the folks who have pre diabetes and obesity? And this is, you know, diabetes is the tip of the iceberg. Right. We have a whole society below that where we need to drive impact because we can't just medicate everybody in the country. So really thinking about the root cause and finding the right nutrition for the individual patient. And this is, this is part of precision medicine, right? Personalizing your diet to what works for you. And it's hard work. I mean, what our coaches and clinicians do at Virta, it's a daily, again, like a white glove experience where we're getting that data, we're doing that positive feedback to make those changes to learn and course correct when things aren't going well, to celebrate when we get those lab reviews. So really, you know, it has to be a very patient, centric, holistic approach. But so I think there is a role for these medications, but I think we need a better solution as a population.

But is your belief that if people were able to adhere to a diet that was right for them, that these drugs are redundant?

I think so. I think if you could prevent. I mean, I'm of the mindset prevention is always better. Less is more. So if you can teach people to eat well and keep them healthy, that's better for everyone. They feel better. They have all the other non. Forget about just the metabolic risk. Think about neurocognitive risk, cancer risk. There's so many downstream things that just by eating right, we can fix. And then I'll just really quickly say, like even sort of transgenerational, like when young adults who are in their prime reproductive years, when they're metabolically unhealthy, we know there's all this epigenetic changes that drives the next couple generations to have metabolic dysfunction. There's real implications for populations when you teach them how to eat correctly. The last thing I'll add is diabetes disproportionately affects minority populations and those with less socioeconomic means. Imagine if we could improve that without costly medications and prevent it and close some of the complication gaps and the death gaps that we have in the United States.

Yeah, I know, absolutely. I mean, the health disparities are huge. And.

There'S a whole food inequity issue and nutrition security issue, and there's all.

The ways in which and equity around getting medications.

Yeah.

Accessing expensive medications and accessing expensive technology like cgm. There's all kinds of equity issues. So what if we went to the root cause and just helped people be.

Healthier from day one and you know, it failed miserably. Right. Because if you look at the, the national approach to addressing diet and lifestyle, our recommendations, our guidelines, our best efforts to help people eat better just have failed miserably. And they failed in my opinion because we are not understanding the nature of behavior change and we're not understanding the nature of how people need to shift and how people need to actually understand what it takes to actually make a lifelong change in their, in their behavior. And I think, you know, I discovered this after working with Paul Farmer in Haiti during the earthquake that was in 2010. I got to know him and his work and you know, he was able to cure TB and AIDS in the most destitute places on the planet. In Haiti, where the public health community given up because it was multi drug resistant tuberculosis, the drug regiments were complicated. You know, the, the that you had to be on dose on schedule and people didn't have watches, they didn't have clean water like so they just kind of gave up. And Paul Farmer realized that it wasn't a medical problem, it was a social problem, a structural problem. And he basically trained thousands of community health workers, neighbors helping neighbors, to change their behavior and to support their, their life. And, and I, and I applied that in a model at a big church in California called Saddleback Church, where we got 15,000 people to work in small groups to change their lifestyle together because of that high touch and that cultural shift that sort of led them actually to be able to do the things that actually work. And so I think that's what's unique about virta. It's not just understanding the science of metabolism, the science of metabolic dysfunction, the science of how we apply nutrition as medicine or ketogenic diets as a key therapy. But it's this other piece that has been completely neglected in healthcare, which is the way in which we need to deliver healthcare, which is through a high touch, connected, supportive environment. Whether it's coaches and doctors and nutritionists supporting patients, or whether it's people helping people. The science behind this is quite good, but it's been ignored because it's not reimbursed. But what's exciting about Virta is that you're showing not only does it work, but that you're actually saving approximately $6,000 per patient. You Know, and I, and just in Medicare, for example, just because I was testifying in Congress last week, you know, sharing with the congressman how, you know, we have such an enormous cost of diabetes and we're able to actually address that by, by actually doing the right thing and using this model to actually help reverse diabetes.

Yeah, I would add there, Mark, that the nutrition science and the care delivery model and the third piece that I think has been behind Virta's, what I might call early success and impact is the business model. And it may sound like MBA talk, but this is a very, very important thing because if you don't have the right business model, you can't get anywhere in US Healthcare.

And it's. So our business model is very, very rare in US Healthcare in that it is a true win, win, win. So what we do is virta care is 100% free and no, I'm not joking, 100% free for the individual patient. So that's a win for the patient. But then the payer that we work with, which is either self insured employers like Fortune 500 companies like UPS or United Airlines or US Foods, like we work with nearly 500 large employers and then help plans like California, Humana and some government entities. So the payer pays for the treatment. But here's the best part, like you said, they save a lot of money so they pay less than they save.

That's right.

So that's the second win. So it's very rare in US Healthcare. Usually it's like, oh, this is a beautiful new molecule, big molecule, large molecule. Or like a specific cancer treatment, say.

And then it's million dollar treatment or $100,000 treatment. And then there's this trade off, okay, that's clearly it's going to improve, save human lives. But can we afford to cover. But in the case of reversing chronic disease like type 2 diabetes, we literally go to a large employer again, like US Foods has been our client for a long time and we say, guess what? We can reverse diabetes. Make your employees happy and more productive and you make money in the process. And this is safe. Here's the evidence published, period. What is there not to like? You make money and you save lives and families and improve lives for your employees, like high five. And I'm not saying it's been easy. We work with I think 530 customers so far. It's still hard. But so anyways, I just wanted to highlight that if people listen like, oh, it's intensive care model and this must be some concierge thing that's going to cost 50,000 a year. No, it's free for you.

Yeah.

And so, so when you combine those things, the outcomes through nutrition and care delivery and in a business model, that honestly to me feels like a win, win, win. That has allowed us to scale pretty fast. And I always say this very openly because I want others to copy this. We need more innovation in healthcare like this that isn't, oh, here's the million dollar miracle cure for this thing, and then everyone's fighting who's going to cover it.

It's crazy. I mean, when I was in Congress, I was testifying, you know, the United States government, federal government, spends about a billion dollars a day on diabetes care, direct diabetes care, and the Medicare population, 18 million are diabetic. If this was applied across that population and everybody did, would be over a $90 billion savings for the federal government a year. And that's just this one issue. And I think it also cuts across all these other health conditions. So I think the economics makes sense, the science makes sense, the delivery model makes sense, but the barriers are really that the traditional academic perspective is that this is not the treatment and it's not really sort of taken up by the American Diabetes Association, American Heart association, by Medicare reimbursement, which we're trying to change. I advocated actually as part of my testimony for a national diabetes reversal pilot program where we can actually demonstrate this within the Medicare population and show that this actually works better, that it's a triple win, as you said, and that then actually maybe the entire health insurance industry would cover this. And I think it would be a good thing in many ways because it's, it provides the right drug with the right delivery mechanism to actually create the most effective outcomes and to reduce costs the most. And that's what we're missing in American healthcare is a delivery model and a treatment model that actually works better. And I think for people listening out there, people struggle with weight, they struggle with how to regulate their appetite, they struggle with knowing what to eat, they struggle with how to change their behavior. But you know, what we're talking about today is.

A lot of both clinical evidence, research evidence, and the sort of science behind how we can actually do this at a population level. It's not one on one, like you said, with a concierge doctor. And if everybody wants to see me, I can help people lose £100, £150. But they're working with me closely in my team, and it's one on one, and it's intensive, you've learned how to build something that's scalable to the entire country and maybe even a billion people.

Yeah, absolutely. And you mentioned that people struggle with metabolic disease and nutrition 100%. And I guess, you know, I mentioned I'm a triathlete and entrepreneur this and that. So I just want to say, I hear you. I see you. I can empathize with you. And I say this because 100% of the patients that come to Virta, which, again, now is more than 100,000Americans, they have tried somewhere between three and 15 different diet programs or different times, and they failed every single time. So if somebody's listening and say, like, well, I've tried everything and I've failed, I just want to say, I see you, I hear you. You're not alone. That is the story of practically every single American struggling metabolic disease. You haven't failed. I think the right message is the program of the diet failed you. The program or the diet failed you. And I. I say this with high degree of conviction because that is the case. And there is a way to help you succeed. When you have the right support and the right nutrition science, you can succeed. But this is the story of everyone. I've tried five things. I failed. I'm a loser. I'm a failure. You are not a failure. The program has failed you. You haven't failed.

And, Grisha, why do you think medicine so resistant to this? I mean, you come from the center of sort of the heartbeat of traditional medicine at Harvard and Johnson Diabetes Center.

Why do you think there's such a resistance to accepting this as a effective model?

Well, I think part of it is that we all sort of have our belief systems that we grow up in and we're mentored in. And, you know, even with research, when. When a trial is negative, it's very unlikely to get published. Right? So we. We sort of perpetuate biases, and in medicine, and so there's. There's sort of like this bias built into the science. But I think slowly we're going to see that change. And I think now that we're in the age of more data and big data, like, I think the outcomes speak for themselves. And I think what we've just been saying, like, the. The triple. The triple aim of better outcomes, better patient experience at lower cost, that that is going to drive things forward. And I think Sami's point of saying, like, the business model is really important. And I don't think I would have said this four years ago, but after working at Virta, because No, I mean, I practiced in a model with where I was in that fee for service. Even though I was an academic clinician, I was in that fee for service model. And so even if I provided excellent care, I needed to spin my wheels and race through my clinic and try to get everybody through as fast as I could so I could stay on schedule and then, you know, do my pajama charts late at night because I don't have time to do any of my documentation, which is excessive. It's burning out clinicians. So I think until we fix the way we reimburse folks who take care of preventable diseases, it's going to be hard to change. So I think the business piece of it is really important.

But what you're talking about is not just prevention. You're talking about reversal and treatment. So I think people think of diet and lifestyle as it's great prevention. Okay, I can prevent diabetes, I can prevent heart disease. I can prevent these diseases if I exercise and eat well. But no, no, no. So what you're showing very clearly is that lifestyle is a more effective treatment. And I think as physicians, our oath is to help our patients. And if there was a drug that worked better than diet, you and I would both use it. But what we're hearing really from the science here is that we're not using the most effective drug. And it's because we're not paying for it and not paying for the service of actually delivering this sort of supportive, continuous care model with the right education, with the right support, with the right knowledge. And I think so what you're showing also that people are, you know, like, nobody wakes up and goes, hey, I want to be diabetic, right? I want to be overweight. People want to do the right thing. They're trying to eat better. They've, like you said, they tried all these diets, they've taken all these medications. The doctors are doing their best to actually help manage the disease, but they're barking up the wrong tree because they're not actually using the right tool and they're not using the right delivery model. And that's really what Verta, I think, has pioneered. And I think for me, to me, it's one of the most exciting things in healthcare to see what you're doing because you're outside of healthcare, you're disrupting it from the outside. It's getting certain attention from certain payers, like private insurers, even Medicare Advantage. And I think it has the potential to really revolutionize how we both think about using the right treatment for each patient and also the delivery which has got to be through behavior change models that work. And I'm curious how you came to that behavior change model because yes, ketogenic diet is great, it works, but tell someone to do it, good luck, they're on their own, they're not going to be able to figure it out.

I think one thing to add on that is because we're this continuous model where we have sort of the luxury of a two tiered rounded system of coaching and clinical team, we're really able to give robust education and resources. And I mean, I think that's one thing. Sarah Hallberg, who ran the IUH trial, she had just finished reading her book recently and one thing she said is that we often in medicine underestimate patients ability to understand physiology and their own health. And when you actually educate them and show respect and share that knowledge with them, it's very powerful. So I think, you know, old school paternalistic medicine, I tell you to take this, you take this, don't question me, is what we've done in medicine. We've done that for a long time and this is much more of a shared decision making. Let me explain to you your physiology why we're doing this. We make the changes. Guess what, you're logging it into this app on your cell phone. Your doctor and your coach are seeing it. We're adjusting your meds in real time. It really makes that knowledge actionable. So really sort of respecting patients intelligence and sharing what their physiology is doing and sort of on real time driving that forward. It's a real positive feedback loop. I think that's a big piece of it.

I agree. I mean I always say as a physician, that's my experience too, that you know, I think I was biased. I had the assumption that people knew, understood, just didn't do it because they were lazy or they were gluttons or they whatever. There's all these judgments about, about obesity and diabetes that you know, the people just didn't care and, and I realized how flawed my own thinking was and how it wasn't their fault that they were living a sea of misinformation around nutrition. That was not accidental. That was promulgated by a food industry desire. It was desiring to get more stomach share and that the scientific community was corrupt as well because it's highly funded by these big food companies that the NIH spends I think 0.02% of their budget on nutrition science, most of which isn't even the right stuff anyway. And so we've had this sort of system that is completely neglected the, the individual patient's ability to take control of their health because they're not getting the right information, they're not getting the right education. And when they are and when they do, people are willing to shift. And I've seen this over and over, over 30 years of practice, when you sit with someone, you look at their data with them, you explain their biology, you say this is what's going on. Whether you're carbohydrate intolerant or your gut's unhealthy and you need to eat this or do that. People are willing to do it because they don't want to feel sick and they're trying to do their best, but they're, they're kind of following a path that we set on medicine that's completely flawed. And I think I'm very enthusiastic about seeing how this becomes adopted across healthcare because like you said, if you are showing the data now, you have 100,000 patients. There's this opportunity for the tipping point to happen where this becomes more widely adopted and it becomes actually standard of care. Not just for diabetes care, but the concept of continuous care model of support and coaching and constant interaction, dynamic ways of working with people, with telemedicine, with coaching, with digital apps, with biosensors that upload into the cloud that you can read. I mean, it's a really different era of medicine and I think we're seeing this convergence that it's going to shift us from being sort of burdened with this chronic disease epidemic to starting to shift it. If, if we're actually able to kind of get the kind of payers to start to realize that this is a win for them too.

And I should just, I'm very optimistic and not just speaking my own book. Given the growth that we've seen from, you know, 20 pay your clients early 2020 and now 520 plus, this message of we can save lives, improve lives and you make money in the process. Even if you don't care about the humans, you just want to make money. You should cover pay for virtual like treatments. I'm actually very optimistic that the growth and positive impact on human lives will continue. On the product and behavior change side, I'll just add one more thing. In addition to what Christmas mentioned, just trusting the patient. And internally we use this term that at best we are co pilots on your journey towards better health. We are co pilots. We are not the gaptain, we're not the boss telling you we are co pilots. So just trusting the patient is so important. The second thing I wanted to mention, obviously everything we do is telemedicine. We use AI. It's like software and tech. DNA is at the core as much as sort of patient safety and clinical and nutrition science. But the way we use software is to empower our clinicians so providers and coaches so that they have more time for what we call powerful care moments to drive results. This human connection, real human connection between the patient and our clinicians is very, very important. And like, there's a reason why I, as a CEO, you know, you know, we have close to a thousand employees, but I write handwritten notes, not to everyone every day, but to many people. I will never have AI write those. It's not my assistant who writes those. Guess why? Because I care. But because the whole point of the thing is that I personally write the note and the address on the envelope and send it to you as a note of appreciation. It's the same thing in our care. Yes, we can use AI, yes, we can use software to sort of automate the simple logistical things and provide you support. But there's a point in time where this human connection makes all the difference, 100% difference. And we don't want to lose that. Even if AI technically could deliver all the bits and messages and pictures and whatnot.

Yeah, it's incredible. Well, I applaud you both for what you're doing. I look forward to more and more science and data coming out, to supporting you to help make this the model of care for care in general in America. And I think for those listening, I think we're going to link to Virginia, to health.com, which is the website you can read about the program. I mean, everybody in America is either touched by diabetes or touched by someone who has it or has it or has pre diabetes. I mean, and like I said, 90% of people don't even know they have it. At Function Health company I co founded, we allow extensive testing of metabolic health and we're seeing just such a degree of metabolic dysfunction that nearly everybody could learn how to sort of improve their health. And there's also an incredible amount of research you've published. It's all on your website and it's well as how to engage with the program. So we're going to link to all that and I appreciate both of you so much, so much of what you've done to actually advance healthcare and medicine and kind of wake people up to the possibility that these chronic diseases are not a one way street. And that is what we need to teach America that these chronic diseases don't have to be chronic. I don't want to manage them. I want to get rid of them. And I think you do, too. And thank you both for all you've done to sort of make that happen and continue the work that, you know, Sarah started with you and Sammy and appreciate you're doing now. It's really inspiring. So thank you both being on the podcast and thank you all for listening.

Thank you, Mark.

Thank you.

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