Episode 18: Semaglutide White Paper Research - Lose weight more easily

Today we're going to talk about semaglutide, the injectable weight loss medication. The clinical studies that led to its FDA approval for weight loss and our experience with it at Allure with our employees who wanted to lose weight in our South Carolina location, we did one additional activity. So semaglutide is a drug that's in the form for obesity, is an injectable that's once per week and, and its brand name is WeGovy. There's another form called Ozempic that's the same drug at a different dose that's used for diabetes. Now, these medications are of a class of medications called GLP1 agonists and glucagon, like peptide. GLP1 agonist, it's a peptide hormone that regulates insulin and blood sugar. It has effects in the brain, the pancreas and the gut, probably other organs as well, and helps to lower blood sugar, improve cardiometabolic features in a person that has diabetes or is overweight and helps them lose weight. Now, the drug was copying a pathway of metformin. Metformin is the most common drug for diabetes. It's a generic drug, so you don't hear about it much. It's not that sexy because it's been around a long time. It's very effective. And metformin is also being tested as a longevity drug. So I'm only talking about metformin in the. Because it does play into this a little bit. And metformin works on the GLP1 pathway as well in addition to other other effects. So in the GLP1 agonists were first FDA approved for diabetes. It was noted that patients with diabetes who were using the GLP1 agonists not only had better management of the blood sugar, better cardio metabolic profiles, it looked like they would probably live longer and have less cardiovascular events, but they also lost weight, so they become very effective and comm for the treatment of diabetes. And there's been different forms of GLP1 agonists. And when we're talking about a semaglutide, which is FDA approved for obesity, last year, in fact, it was so popular for obesity treatment that the drug company ran out of it. There's a big shortage at the time I'm doing this recording, this will probably catch up at some point. They misjudged the size of the market, pardon a pun, of obesity and overweight adults and America. Now the indication is somebody who's obese, which is defined as a BMI over 30. And that's basically Your height, weight ratio and there's a scale that's used or they have a BMI over, I believe it's 27 or 28. And some weight related disease such as cardiovascular disease or hypertension, something that can be directly attributed to weight and if the weight came off, you know, the disease might go away. The way they designed the drug was to be a drug you would take to get the weight off the stay on the drug the rest of your life. Now the cost of semaglutide for weight loss is about $1,600 per month. So you know, $20,000 a year plus. And it's something that you take forever. Of course, some insurances, most insurance probably don't cover it yet because it's very expensive and a lot of people don't have weight loss insurance coverage. Certainly Medicare wouldn't cover it at this point. But this was a big moneymaker for the company. So it's shocking that they didn't anticipate the demand and they ran out of it. So what happened in their clinical study is they put people on the semaglutide or placebo, weekly shots for 68 weeks. Published in the New England Journal Medicine in March of 2021. They additionally have them on either the injectable drug or placebo. They asked them to reduce their calories by about 500 calories a day. So if you're eating normally 2500 calories, try to go down to 2000. They didn't specify exactly how to do that. And they also asked them to do some sort of moderate exercise, which would be something like walking 150 minutes a week, which would be like 30 minutes a day, five days a week. So walking five days a week and cut your calories down and take this drug or take this placebo, you don't know what you're going to get and neither will your doctor or the person doing the study. Now, at the end of 68 weeks, individuals who took the injections of placebo or the drug and were attempting to exercise and diet, the ones on the active drug, lost about 15% of their body weight, not their body fat, but their body weight, 15%. So for example, somebody weighed 200 pounds, that would be 30 pounds at 68 weeks, you know, about a year and a quarter. And the people on placebo lost 2.4%. So the person on placebo that weighed 200 pounds would lose about 5 pounds over a period of a year of cutting down their calories and exercising. Now, they didn't control for diet and exercise. They just asked them to do it. And we know people aren't always compliant, especially for a year. And these are people that were wanting to lose weight. So you think they would, you know, have tried diet and exercise in the past. Now, the medication is given once a week as an injectable, what's called a subcutaneous injection. So it's very easy to give yourself a shot. It's kind of like an insulin needle. It is an insulin needle, and you put it in your stomach or your flank or your hip or something. And the medication has a starting dose and a maintenance dose. So the maintenance dose is 10 times higher than the starting dose. But people start losing rate at the starting dose. And this appears to be a tolerance to the medication where you have to increase the dose, increase dose, increase the dose to eventually it's 10 times more than the original effective starting dose to maintain the weight off. Now, what we notice when looking at the study is you'd wonder, when does a weight loss occur and when does the weight loss kind of trail off? And in their study, New England Journal Medicine, In March of 2021, if we look at the first eight to 12 weeks, so about, you know, say, four months, three months, 12 weeks, they lost about half of the weight they would ultimately lose between 12 weeks and 52 weeks. Okay, so the next 40 weeks, they lost the other half. So they lost the first half of the weight about 7.5% or so in 12 weeks, and they lost another 7.5% or so over the next 40 weeks. And then between one year and 68 weeks. So again, you know, 16 weeks later, about four months later, the weight just stabilized. They didn't lose any additional weight, yet they were on 10 times of a higher dose than they were in those first weeks of losing weight. The most rapid weight loss actually occurred at the smallest dose, which was that first four weeks, they lost about two and a quarter percent of their body weight. So we were seeing this rapid weight loss with the starting doses, but as it escalates, why doesn't it work as well? It appears to be a tolerance effect where after so much time or so much medication, the body gets tolerant. They even suggest that if you stop your semaglutide from even two weeks, you start at the lower dose again, because the higher dose gives side effects when you haven't been taking it. But starting at a much lower dose, there's less side effects. However, just stopping it for two weeks, you have to start over again at the low dose. This suggests a very Rapid tolerance and a very rapid extinguishing of that tolerance. Now, the placebo individuals lost weight, and they also lost weight in the first 12 weeks. And. And they continue to steadily lose weight weight up until about 36 weeks when they plateaued and didn't lose any additional weight. So the placebo loss about 2% at the three months, and the active drug group lost about 7.5% of their body weight at the three months and then over the next almost year additionally came off in the group of semaglutide. And the placebo patients stayed about the same. So that's good to know. You know, we might think about using this for three months and losing weight. Well, what happens when you stop the medication? So another study, this was published in 2022, looks like it was April. In the Diabetes Obesity Metabolism Journal, they did a study where they withdrew the medication, either placebo or the act of semaglutide. But they also instructed the individuals to stop exerc exercising and go back to their old dietary habits, which seems absurd, but the purpose of this study was to prove that to the public and to doctors that you must keep your patients on this medicine forever at $20,000 a year. So in the 68 weeks they had stopped the semaglutide or the placebo, and in this study, this portion of the study is reported, they actually lost a little bit more weight than the primary report. And sometimes it's basically what data set they're extracting, but about 16 or 17% of weight loss. And when they stopped the drug, the individuals gained most of the weight back within about two or three months. And then it kind of leveled off and they wound up at about a year later keeping some of the weight off. About 6, 5 or 6% of their body weight stayed off. So there was 10 pounds or so lighter than they were at the beginning. Even though they had gone back to their old eating habits, they had stopped exercising and they stopped the medication. The placebo group, on the other hand, gained all the way back. So that's an interesting tidbit that even a year after stopping the medication, the individuals on the semaglutide taking it a year and a quarter or so were thinner and probably healthier at the second year, at the end of the second year, than people that were on placebo. Additionally, what they noted was people that had more significant weight loss had the most retention of the weight loss. So people that lost, you know, 25 to 30% of their body weight kept about 12 or 15% of the body weight off, whereas people that only lost a couple percent of body weight, as well as those on placebo, gained it all back maybe in, plus some. So that's good to know. So what can we do with this? Well, first off, the drug is, you know, very, very expensive. About $1,600 a month at this time. Insurance generally doesn't cover it because a lot of people don't have coverage for weight loss. I consider it a disease by most insurance companies. So it's not practical to take something that's that expensive. And additionally, there's some, currently some, let's say, generic or compounded versions of semaglutide available. What happened is when the FDA gives approval for a drug, the company also has intellectual property or patenting on the drug for, I think, 20 years or so. And the FDA approval is approving the drug, and the patent protects the manufacturer to make it. Well, when the company ran out of the ability to manufacture the drug because they don't have the supplies, compounders were allowed to make it according to the fda, because it's no longer commercially available. So compounder can make drugs that are FDA approved and not commercially available. They can just make it. And that's what they're doing right now. In order to not step on the patents of semaglutide, my understanding is they're adding things such as B12 or carnitine, other things that reduce some of the side effects of the semaglutide, make it unique. So they're not bothering the patent protection of the wegovy. And that's something that probably wegovy will go after at some point. I'm not sure what the whole status of that, but they can legally compound it right now, and it's a lot less expensive. So we've been using this in our patients, the semaglutide. And I wanted to see what would happen if we could change our mindset from being a drug you take for the rest of your life the drug you might take for a short period of time, mostly during that rapid weight loss phase, which occurs in the first, you know, three months or so, and then use another less expensive and very safe drug to help you keep it off and let the tolerance to the semaglutide go away, get extinguished, and perhaps do another round a bit later on if you need to lose additional weight. So this is our experience. So in our office in South Carolina, we have employees that wanted to lose weight, and we started them on semaglutide at the lowest dose. And Escalated it as the company does. We mirrored the same dosing, pretty much the same dosing. We used pretty close to identical same dosing. And we escalated every four weeks for 12 weeks. And then we switched them over to metformin, which is the number one drug and well, number three drug in the world. Number one drug in the world for diabetes, which is also being tested as an anti aging drug. So metformin appears to extend lifespan and health span. I'm taking it even though I have no diabetes, no obesity or no overweight because it's been shown to extend the life in animals and even in humans. And still studies that have been done, there's a large trial right now just using metformin alone for life extension. A lot of anti aging doctors know we're taking it ourselves for that purpose. So we know it's safe. We know it acts on the same GLP1 pathway in a different fashion. It upregulates GLP1, whereas semaglutide agonizes it, meaning it makes it work better. So semaglutide pushes GLP1 forward, which is a favorable drug for weight and cardiometabolic features in your blood sugar. And metformin elevates the level. So we have kind of a push pull. So we put the individuals on the dose escalation of semaglutide for four months. Then we had them stop it. Right when they got to the maintenance dose, which is where maximum tolerance occurs and weight loss slows down. We switched them over to metformin at a dose of 850mg, first at once a day and then going to twice a day. Metformin is better. Started out, you know, once a day and then twice a day after a week or two because there's some gastrointestinal side effects can occur from taking too much at once. And here's our outcome of our individuals. So the weights, the starting weights were 149 to 237 pounds, mostly women, one man, and again 149 to 237 pounds. And let me pull up their BMI. The bmis ranged from. 26.4, which is pretty close to normal, weight is slightly overweight, to 41.4, which is extremely obese. So there was a big, big range. So 26.4, 29.1. Those are both in the overweight range. 32.3 obese, 37.1 and 41.4 lasso being obese and extremely obese. So what happened? Well, we used the semaglutide for three months, switched over to Metformin for about a month and a half. And we've. These are the. And we did one additional intervention. We didn't ask them to exercise, but we ordered Mediterranean food, Mediterranean diet for our staff, which in this case included poultry, vegetables, green leafy vegetables, potatoes and fruits, some nuts and beans, legumes, and no red meat, and no processed food whatsoever. So four days a week, they work four days a week, and four days a week, they for sure got a healthy Mediterranean meal. Now, whether or not they bought additional stuff on the side, we didn't control for that. But what happens in a group of people working together versus the clinical study, they all know they're getting the active drug, nobody's getting placebo, and there's some social commitment to eating healthy together. And in the clinical study, they lost about 15% of their body weight in a little over a year, 68 weeks. What would happen if you all ate together and you for sure had one healthy meal a day? On this group, the average weight loss was 24 pounds, and it was 24 pounds plus or minus 4 pounds. So the least weight loss was 21 pounds. The most weight loss was 28 pounds. And this is a very interesting range because they started at significantly different weights. And we assumed people that were heavier would lose weight faster, more. Well, that did happen. The people that were heavier tended to lose more weight, but the people that were just overweight lost 21 and 24 pounds, which made them normal weight, not underweight, just normal weight at the end of this trial run. Additionally, during the metformin switchover phase, nobody gained weight, so there's no weight gain. They kept it off. Now, the ones that are now normal weight are just going to stay on the metformin. They can certainly do that for the rest of their life if they choose. It's safe to take long term. And the ones that are still overweight, because they had started out extremely obese, they're likely going to do another run two months after they stopped the semaglutide, but starting at the lower dose again, the dosage that has the most effective weight loss. How about body weight percentage? So in the clinical study, the average weight loss was 14.9% at 68 weeks. And in the placebo is 2.4. We saw an average. The weight loss was 10% to 14%. So the lowest amount of weight loss was 10% of body weight, and the maximum weight loss was 14% of the body weight. Now, the person that lost the biggest percentage was also the lowest BMI, the thinnest person in the group, that was 141 pounds, that went down to 128 and losing the most percentage and the least went down 21 pounds, which was a lower amount of pounds lost. So the body weight loss was substantially more than that in the clinical study, almost twice as much. So in the clinical study, it was about 6 or 7% of the body weight. About half was lost in the first four months. I'm sorry, three months. And in our group, it was average of 12% body weight was lost in four months. And this was three months of active drug in one month of washout with the metformin. So it's very interesting. We'll see how this plays out over time. We have patients that are on metformin. I'm sorry, on the semaglutide, the least amount of weight I've seen clinically, in my experience, I'm not seeing all the patients has been ten pounds at about two months. That was the least and the most I've seen has been 70 pounds in three months. And that was somebody who was really heavy and it was a man who made some additional efforts. But all in all, we've only had one person not be able to take the medication because side effects, it causes gi upset for some people. She had a lot of indigestion from it. A friend of mine had taken and he got indigestion from it. But in general, I've heard most people, they say they get maybe a little bit of nausea at first and it just goes away. They tolerate it well. So semaglutide for weight loss, it was designed to be a lifelong drug, which is very expensive. And I'm thinking about it differently about putting a little bit more effort into the lifestyle change, being really specific on a Mediterranean diet, you know, adding extra virgin olive oil, poultry and fish, but not as the main source of the calories. My main source calories being from vegetables and legumes and whole grains. This is the most favorable weight loss diet in the clinical study where they only lost, you know, 15% at over a year. They didn't really give them any kind of dietary instructions that were, or hold them to it. They just really didn't buy their food. And we at work, we've always bought food for our, for our staff. We have for years anyways. So that's, that's been our experience. Hopefully this is helpful for people to see what your alternatives are. Besides being on a $20,000 a year drug, there's maybe alternatives, even when they get back on board with having the commercially available product, it might be that you do three months, which is a lot cheaper, or you might use a compounded version that's available as of time of this recording. They are available. We're seeing more and more pharmacies coming through, making it, and it might drop the price even further, but it's way below the $16 a month. So. So semaglutide for weight loss. In summary, we saw an average of about 12% weight loss, which was 24%. I'm sorry, 24 pounds plus or minus 4 pounds. This was in four months with three months on the drug and about six weeks on four to six weeks on metformin. And nobody fell off it because of side effects in that grouping. And we're using the same medication pattern in our patients. So thank you very much.