Transcription
Welcome to On the Pen. I'm your host Dave Knap, man of the major. That's why I'm here. You are on the pen. This is Hamone. Hamone, welcome. How you doing today?
>> I'm doing pretty good on this freezing cold western day.
>> It's been a terrible, terrible go here in Iowa. So, we had like 50° weather over the last couple days, which has been crazy for Iowa. And then the day that I choose to wear flip flops out, it reverts back to 20 degrees.
>> I didn't even realize.
>> Got got my flippy floppies on. Just dreaming of the days where I can hang out and do these live streams at the camper again. Uh, welcome though. We do obesity medicine news from the patient perspective so that you can have more competent and confident conversations with your doctor. I spin on my chair. Drives half of you nuts. you put it in the comments and let me know how much it drives you nuts. Hamone's here because she's got a whole list of things that uh she thought that you might be interested in talking about today. But before we get to those topics, I wanted to get to the the topic that we put on the thumbnail. And that is something that we talked about briefly in the podcast yesterday. If you're not a listener of the podcast, I don't even know what you're doing with your life. But yet, but yesterday, we dropped our Tuesday podcast. It drops every Tuesday uh on all the platforms that you like to get your audio podcast from. It's called On the Peng News. Uh you can find it wherever you get your podcasts. Uh but we talked real briefly about how one of the things that's been talked about over the last few days at the JP Morgan Chase conference, the investor conference out on the West Coast, uh Lucas Montars, who's one of the one of the executives for Eli Liy, sat down with Bloomberg and ended up saying that they expected the or for pill to release sometime quote sometime in uh or as early as as early as quarter two.
So, as early as quarter 2 is quite a jump from what we were told was going to be early in 2026. We anticipated that with the fasttrack, the new, you know, one month fast track from the FDA, something that we've known for some time now that Lily received from the FDA, that we would be seeing this thing by, you know, February, sometime February, March, the latest. Um this uh this is breaking news because ultimately uh a delay to as early as quarter 2 could mean as late as beyond quarter 2, but certainly as late as May. Um and so Novo is really getting a huge jump start with their Wiggoi pill uh which I will be starting here in the next day or so as soon as it's locked up in the mail. So, uh, we'll wait to get that in the mail. But I digress. Are you starting the Wiggoi pill? I know a lot of you are intrigued by the Wiggoi pill. That's the once daily pill. You have to take it first thing in the morning on an empty stomach. And if you don't, it won't work. But if it does work, it works almost as good as the injectable. So, over 64 weeks, the pill gets you about uh 13 14% weight loss in between 13 14%. uh in 68 weeks, so one extra month. The injectable version at the highest dose gets you 15 to 16% weight loss. So they're about the same uh when you factor in that the clinical trial for the shot had an extra month on it that the pill didn't.
>> Which is wild.
>> Yeah. I mean, you're talking about efficacy that we've received with WGO injections in a pill. So if you're interested in trying the pill, uh they did launch it. Our friends shed launched it today. So, if you want to uh explore your options, talk to a provider uh and see if this might be the right step for you, whether you're in maintenance or just getting started and don't want to try the injections. Uh you can check out our partners' shed. You can actually go to OTPs.com, click the link there. It just funnels the traffic through uh OTP's link, which helps to promote the podcast a little bit. Uh use code OTP25 and you're going to save $25 off of that. uh you can start that pill for I think $149 a month. So, not only is it perhaps easier for people who are, you know, averse to taking injections for whatever reason, but starting this thing uh for $149 a month is is crazy crazy compared to what you had to if you wanted that kind of efficacy out of the Wiggoi shot one year ago, you had to pay without insurance, you know, five six00 bucks. So, and the and the list price was 1,300 bucks. So, we're talking about one year. Um, and the pill version is available for 149 bucks to start. You get kidding me? Uh, it's just crazy how much this landscape has changed over the last year. Uh, let alone the last three years since we've been doing this here at On the Pen. I want to take a moment and welcome in to the chat today uh some of our OGs. We got Ruben and Sue the Dude. We got Me Fancy. Uh, we've got Chi-Chi Lover. Hopefully that's not dirty. Uh, Dena, Nicole Sullivan, Jillian KD is in the house. Deb Zimmerman, Fresh Eclecticism. I always say eclecticism. I don't know why. Eclecticism. Uh, Mike Jacobs is in the house. Down in the Dale is in the house. Mujaro with Journey with Pam is in the house. Welcome, Pam. Uh, Penny is in the house. Pam Bone is literally in the house. And Jay Neb's in here. So, we got a whole bunch of folks in here. So, welcome. Good to be here with you all.
Um, so if you have uh Oh, let's let's see here. I want to I think we need to clarify what about the same means. You're talking 20 or 30 times as the milligram amount weekly. That's not about the same to me.
Um, well, you're not your body is not processing the same. You're not your body's not processing to 20 to 30 times the uh active pharmaceutical ingredient. It's absorbing about the same. That's why you get the same results. It's the same molecule. You're taking it orally, and yes, you're taking a 25 milligram uh oral tablet once a day, and you're taking a 2.4 milligram shot once a week. So, you're taking 10 times the amount per day, but your body is only absorbing about 10% of that pill. Um, when you think about, you know, getting that steady dose of of medication, I think it may be even less than that. I think it may be fractions of a percent to be honest with you. Uh, but your body's not absorbing most of that. That's why the pill comes, I call it the gremlin pill. You have to take it on an empty stomach because peptides get destroyed immediately by the stomach acid in your stomach. And so what they've done is they've added a little a little helper called snack technology which is just a fatty acid that they wrap this thing in which allows it to to survive very little amount of stomach acid. That's why they say take it with a si they actually what they say is take it with a sip of water first thing in the morning on an empty stomach and then don't eat for 30 minutes. They say you can take up to 4 ounces of water, but the less the better because the more that you have in terms of uh of stomach acid, you can render this pill completely ineffective for that day. And of course, it's got the semaglutide has a halflife of about seven days. So, you're trying to build up uh your your body uh you know, you're trying to build up your blood plasma level. So, if it doesn't work for a day, you're really affecting your treatment for the entire week. So, it's very important that you take this pill first thing in the morning on an empty stomach, which is why Lily has touted or forgrron as better uh than wiggoi because it's more convenient. You don't have all these rules, but it's a small molecule uh GLP-1 versus a peptide GLP-1. And Michael, I now that I I'm thinking, I think I know who you are. And so, I know that you know everything that I'm saying here, but um but I know that many people who are watching and listening don't. Um, so your body is definitely not absorbing 20 to 30 times the peptide uh that it is if and you take an injectable. You just need that much more because your your stomach acid is is gobbling up most of the efficacy.
>> So,
>> Yeah, they did extensive testing to make sure that that's what ends up after it goes through your body. It's
>> extensive testing and
>> and the thing that I'll say too is they they invested$2 billion dollars to buy the technology to do it. So that's why I say when you find compounded versions um beware because we just don't know what type of technology they're using to wrap that peptide and make it orally bioavailable at all because there's no uniformity across different teleaalth platforms or different compoundies. It's more important to know the compound pharmacy that you're using and maybe what kind of technology they're using if you're looking at compounded oral options. But honestly, if you're looking at oral options at all, just go with the branded because the branded versions are proven to work and you know that you're not going to be wasting your money. Even if the compounds are cheaper, don't you think that knowing that it's going to work based upon clinical trial data is more assurance than wasting several months on a a cheaper version that just doesn't end up working at all. Um, that would be my my take on it. If you have a question, please drop a Q in front of it to let me know that's something you'd like me to address. like Sue the dude here, he said, "Do some people have more stomach acid say due to ulcers? I wonder if this will work equally for everyone." I think that what you see across clinical trials is averages uh based upon how people respond, but certainly there's going to be some variance. So, you'll want to work closely with your uh medical providing team to make sure that you're getting the efficacy that you need if you think that you may be one of those person people that produce more stomach acid. Um, you know, maybe or forgrron might be a better option or maybe looking at the injectables. But you know try it and make sure you stay in close communication with your doctor would be my recommendation. Research pulse says 25 milligrams wiggi pill time 7 is 175 milligrams a week versus 2.4 milligrams for wiggoi injection. 73 times more API in the pill than the shot. Bioavailability of the pill is between 1 and 2%. Thanks for the heads up on that research pulse. Always backing me up with the data. Uh Michael says I guess my concern is more with side effects. I just want people to realize how much more they're taking, not how much they're actually utilizing.
Yeah. Um, again, your body's absorbing it the same and the side effects are pretty similar. Um, there was less diarrhea with the pill than there was with the shot, but more nausea with the pill than there was with the shot. But these are pretty marginal numbers uh when you look at the data from the clinical trials. But uh all things to to be aware, they're not exactly equal when it comes to the side effects, but the side effects are they mimic, you know, in general the rest of the class of medications. They're they're nausea, vomiting, diarrhea, um constipation. Funny that a pill can cause nausea and or sorry, diarrhea and constipation at the same time, but go figure. So So excellent point. Um, you know, do be aware. Um, I definitely uh I'm I'm not uh trying to push anybody to one way or the other, but just I I'm excited about the expansion of options uh that we're seeing in the in the drug pipeline and now in the real world even. I think it's it's pretty amazing. I wanted to flag just a couple of of things yesterday before we get to the stuff that you have for us, Hamone. and that is that um e Eli Liy uh CEO Dave Ricks actually spoke at the JP Morgan Chase conference yesterday. Uh there wasn't really a lot of breaking news, but here here's one thing that he did say that I found to be the most interesting. Right. So, we we learned from the CEO, Mike Dudstar. He's the new CEO of Novo Nordisk, who I believe has done a marvelous job just from from a somebody who's a marketer, I guess, for a living. They have done a marvelous job rolling out the Wiggoi pill, leveraging the teleaalth platforms to help spread the word about their medication, um to leverage their marketing teams to get people excited about the the oral. So, if you're an investor in Nova Nordisk, I think you have to be pretty darn happy uh with the way that the Wiggoi pill is rolled out early on. Um, that said, we heard from Mike Dudstar thatund or 1.5 million people are estimated to be on compounds. That was one of his statements at JP Morgan in in addition to basically saying, you know, that he finds it interesting that the teleaalth platforms really learned how to meet patients where they are at and talk to patients the way patients wanted to be talked to and and just really met patients where they were at way better than pharma did early on. And so they're trying to shift and pivot and that's why you see this DTOC move. Um, but 1.5 million people on compound. This is the interesting thing that we heard from Dave Ricks from Eli Liy CEO of Eli Liy and that is Lily Direct. Their direct to consumer platform which they did launch before Novo launched theirs, is doing about one uh helping about 1 million people per month.
>> Wow,
>> You know, this could be possibly according to Rick's the most successful online pharmacy in the history of the United States. Um, it's it's that's a huge number. Now, I I would venture a guess that if we got to the real number of the amount of people on compound that there may be some of the large 503bs that at the height of the shortages um were maybe rivaling that. I don't know. That's a million's a big number.
>> Could be,
>> but a million people on Lily Direct and it's growing rapidly. So, in the next earnings call, what we're going to be interested to hear is is it continuing to grow at the same pace and investors have got to be loving that. Uh, a million people. What a successful launch that has been. I'm still sort of like I'm torn because from the patient side, patient advocacy side, we advocate for accessibility and Lily Direct has certainly done that. Novocare has certainly done that. It's brought medications to patients for cheaper. Um, I mean, just look at the price of the Wiggoi pill. I feel like it's started a little bit of a price war between these and we're actually seeing meaningful drops in the cost of these medications. But I don't know that I love the consolidation of the pharmacy aspect being consolidated to
>> big pharma.
>> Yeah.
>> Right. Anywhere you see a consolidation of industry, it usually ends up really bad for the consumer in the long run. Look no further than insurance companies and how after the Affordable Care Act, they all gobbled up the pharmacy benefit managers and now you know all all the big pharmacy benefit managers are under the same umbrella, same parent companies as the insurance companies.
>> Yeah.
>> And did that work out well for the consumer? H no. I mean, people are getting just rad over the coals, which is why you have this whole move from Pharma to to sort of claw back some of that money and say, "We're just going to go direct. we're going to go around your your, you know, system that's basically designed to screw patients over and gatekeep and and, you know, make money with rebates and we're just going to go direct to the consumer at half the price that, you know, you're offering it. Um, so just been very interesting to watch this whole thing unfold, but I'm still kind of up in the air. I'm curious what you all think about the consolidation of um the pharmacy and the direct to consumer aspect of of that getting consolidated to big pharma. Um, I like it for obesity medicine. I don't know that I love it long term for the entire system.
>> TT has a question this morning. Uh the compound isn't much cheaper than the branded since Lily uh lowered the rates for Zetbound and now you can get the pill for $149.
Yeah, it's I think TT I think it's an excellent point that the this will force down the price of compounds ultimately, but I think right now the pie is so big for obesity, no pun intended. I don't know why I have to to come up with something other than pi. Um or do we I'm sure we could debate that all day. Should we call it the obesity pie or should we call it something more politically correct? We're going to stick with pi uh for today. the pie is still big enough that I don't think they have to adjust their numbers because they're all sort of vacuuming up customers from social media. And most of the people that are on there aren't like you and I, TT, that we sit around and we watch news programs about these medications and we stay super ultra uber informed about these medications. We know when the pill is launching, we know when the pill is delayed. We know how much the pill is going to be. Um, I think they're they're still sort of thriving on the lack of education that's out there, which is part of the reason that we exist because ultimately we would like to educate everyone in the world about the how to access these medications, about the price of these medications. And the more people that get educated, a they're going to have more competent and confident conversations with their doctor, which means they're going to end up healthier individuals at the end of the day. But the second part of that is they're going to become aware and they're going to become educated consumers and they're going to know uh what the cost is. And so if they know that they can go get the same efficacy out of the Oiggo pill as they can potentially what they're seeing out of their injectable compounded semaglutide, you know, I might go to the branded medication, right? Um, so I think it's a really good point that you make, TT. Um, and I appreciate you being here again. Thanks for hanging out with us a little bit today. Appreciate it.
Um, vegetable pie. Ruben says vegetable pie.
Um, so, so, uh, Sue the dude says Zach Rutano was on Fox Business this morning. Yeah. So, one of the things that we covered yesterday in the podcast was that, uh, Rorow had a kind of a big announcement. It's kind of lost in all this other news uh, that's been going on, but Rorow uh, announced a partnership with Amgen. So Amjen is the maker of they don't have any GLPs on the market but they're working on maritide, which is a GLP-1 receptor agonist and a GIP blocker. So the opposite of trespide is a GLP-1 receptor agonist but it is a GL GIP receptor agonist also. This drug blocks GIP but it gets similar weight loss in early clinical trials. Um, we did learn from the from the Amgen executive that they have some data that lacks a whole lot of nuance and and really it I don't even know how much it's worth talking about because we need the data surrounding it. But they said that patients maintain their weight loss from maritide for two years after going off the medication which is the complete inverse of anything that we've seen from any of the other precursor incretinics. But we'll wait for the data to really get super excited about that. But Amgen is that company that's working on Merit and it's a later stage um, you know, it's it's you know, maybe a year and change off from being submitted to the FDA. They'll probably get a prior uh or a fasttrack authorization because their version of the the injection you only have to take once a month or even some folks are being dosed once a quarter with this. The the plus side is you take it, you don't have to think about it for three months. The downside is you take it, you have side effects, you have side effects for three months. So I don't know. I've always been kind of like I don't love maritide for that reason. And and like if it was a GLP1 plus GIP receptor agonist, I'd be more inclined to be excited about it. But because it's a GIP receptor blocker and we know that the GIP component of trespide is what makes it oftentimes much more tolerable for people to take than say ozic or wiggoi semaglutide, which is a straight GLP1 receptor agonist because it's more gip and that gip seems to help um soothe ematic issues soothe nausea soothe uh those kind of vomiting diarrhea type issues compared to semaglutide alone and so when you block it I think you tend to what we're seeing is some evidence uh potential evidence that may show us that when you block it, you sort of get the opposite effect and then you're stuck with that for 3 months. I don't know. I just have never loved maritide. But but Amjen is an interesting company and they're partnering with Row, the teleahalth company uh that I've advised for for a couple of years. Um, Rorow is now working with Amgen to sort of collect data on accessibility and collect data on insurance coverage to help Amjen when they launch Merit sort of bring it to market in a way that allows patients to access it quickly through their insurance. So maybe they're taking a little bit of a different track from Lilian Novo rather than just saying we're going fullbore cash pay. That's what we're doing. Um, and we're going to we're going to actually partner with these uh insurance companies are going to learn the pain points. We're going to learn how to you know, it'll be interesting to see how they can leverage that data uh and maybe move accessibility for maritide uh closer for people who are covered with insurance um versus people who are not. So we'll we'll be interested to see that. Sue the dude said, "Dave, I think GLP drugs are so unique, we can't make broad assumptions on future pharmacy structures. Ozepic is the laboo of medicine. It is it's changing everything."
Um, it is absolutely changing everything. Um, I don't know. I don't I still I still don't I think you're going back to the point that I was making about pharma and owning pharmacies, you know. Well, it'll definitely be something that we have to see how it plays out. I just don't love the consolidation. Just doesn't ever really seem to work out in the long run for for patients, but it is now. Um, and it's uh, you know, obviously we're happy about it in this moment. Um, but what happens when a new administration comes in who isn't hanging um tariffs over the heads of the pharmaceutical companies to get him to bend to his will? um are they as eager to come out with the next generation of obesity medicine or cancer medicine or fill in the blank for any you know chronic or debilitating disease? Are they going to have that kind of um incentive to lower the price of their medication uh or or not? I tend to think not. And then they, you know, when they run all thearmacies and everybody's, you know, you're 90% cash pay for a drug, how how does the landscape change over time? And then what how does that affect the local pharmacy, right? Because I I do think of the independent pharmacy on the street corner. And maybe it's nostalgia. Maybe there's a little bit of nostalgia um that kind of clouds my thinking on this, but like there's something to be said for being able to walk uh to the corner drugstore, drive to the corner drugstore and talk to your pharmacist who knows you, who knows everything that you're on, right? Because so much of our health care these days is disjointed. Like you're getting a prescription for a statin and a and a blood pressure medicine from your cardiologist. You're getting a prescription for your anxiety or your depression from your psychologist uh or psychiatrist. You're getting uh, you know, different medications for allergies from your primary care doctor. And at the end of the day, your pharmacist is the only one who knows everything that you're on. uh if you're getting your medication from here and there and like half the time I go to the doctor's office and they rattle off 40 different medicines and 38 of them I've never heard of. I'm like I must have taken that, you know, once for a cold or so you're still not on that? No, I'm not on the same antibiotic I was in 1997. Um, so it just makes me concerned about um losing that piece of it, right? And so I think it becomes more important to leverage the techn technological tools that we have so that our our uh information isn't so siloed. Uh, but then our information when it's not siloed becomes a lot easier for you know, people to access at one point from a from a patient um information standpoint. And so all of those things sort of become issues that bubble to the top when we when we start to unpack this a little bit. And I just long term I just don't know how much I love it or not. And I think these are the questions that should be at the forefront of our mind. Um, but excellent point Sue. Have you heard anything any admission by Lily that people who are on the high dose ending up with metabolic damage and real problems down the road because of over stimulation. It's a real problem.
Um, I let me say this. Let me say this. So yesterday there was some news. Um, I can't speak to metabolic damage and and issues that these drugs cause metabolically. Like seems like they really fix things metabolically for people. Um, but to you know, I'll I'll entertain your point by kind of talking about a different topic that came up yesterday. So yesterday the FDA removed the suicidality or or asked the pharmaceutical companies Novo and Lily >> to remove the suicidality um labeling from Zbound and Wiggoi.
>> Now my issue with that is is what the FDA cited was 90 different clinical control trials that show that that was not a signal. It was not a signal. But I think where the signal has come from is in the real world post marketing data where where they're gathering um post marketing information and uh they're using probably the uh VE's database and they're using all these things to sort of come up with you know a potential signal to explore. My issue is this. What if what if long-term exposure is what causes um issues mentally for people? Right? The clinical trials are not long. there. You know, this the the surmount trial was 72 weeks long. We're getting a little bit longer trial with reatride uh at 80 80 weeks, I believe. But still, we don't know what after 3 years of dampening down that food noise, which is also more than likely dampening other things. We talk about how these drugs are anti-hided drugs. They're acting on pleasure and reward in your brain. what after three years what does that do to somebody? You know, I've been on Mjaro for three years. Only after three years have I really started to feel this anidonia stuff. And I'm like, it just causes me to question like is that really something that we should be removing because do we really know that that doesn't cause something longterm on the drug?
Do you think the FDA just was responding to pressure because of the massive real world uptake of of these drugs or
>> I don't know what what the FDA gains from that or that or I don't know what kind of pressure would would have happened in terms of I mean this warning seems to be on everything seems to be on everything from statins to
>> okay
>> to uh an allergy pill. I mean, I'm exaggerating, but it seems like these warnings are just about on everything.
>> So, then I wonder why they would feel any pressure to take
>> here. Here's what I wondered. Here's what I wondered because I think it's a fair question because because that was my first thing is like why what do you how do you harm someone by that warning being on there, right? Because it's literally on like every drug unless
>> like be conscious of this
>> unless it's part of a broader campaign to be like, okay, let's just be real. like a certain amount of people in a clinical trial are going to have suicidal ideation or they're going to have these thoughts um like what is actually caused by the drug versus some sort of pre-existing mental condition that somebody's having, right? Um I wondered if perhaps it had something to do with the Medicare thing >> because my understanding is that warning hasn't existed on the diabetes versions of these drugs.
>> Oh,
>> which have been covered by Medicare.
>> So, what and I haven't looked this up. You could chat chat GPT it real quick. But what I was wondering is if this actually has something to do with it being covered by Medicare and maybe some um extra because then it then it makes sense if it was part of like the negotiations of the most favored nations and the Medicare coverage like hey we got to get rid of this because perhaps it opens up um the pharmaceutical companies to additional liability that they didn't have when the drugs weren't covered by Medicare because once you get into Medicare there is a ton of additional laws about marketing and you know that's why that's why people on Medicare can't get the savings cards because you know stupid archaic laws that like you can't promote your drugs with the Medicare population you know so now they're screwed and they can't get cheaper prescription drugs. Um, even the Novo. This is Oh, this is crazy. This is a crazy story. I want to come back to this, but this is a crazy story that nobody's talking about anywhere. Um, the and this was uh my friend Jen over on Twitter flagged this for me, but the Novocare pharmacy that offers the cash pay WGOI deep in the agreements to get the cash pay WGOI is something about agreeing that you're going to buy for the next year. you're going to buy your your Wiggoi through the Novocare cash pay program, which makes me wonder if once these are covered by Medicare, if that would exclude those patients.
>> Oh,
>> So, today those patients potentially buying cash pay would go because it's not covered by Medicare. once it is covered by Medicare in July, will they be excluded from what their insurance is offering because they agreed to buy cash pay at the beginning of the year?
>> And there's nothing like that that exists in in the Eli Liy terms, right? And and presumably it's because Lily launched the single dose vials and they're exclusively the cash pay option, right?
>> But WGO pens, Wiggoi pills are the same no matter how you're getting them. Cash pay, insurance pay, they're all the same. But Zbbound in the vials is its own I don't know what the pharmacy word is for it but it's its own skew. Uh and so
>> potentially what they were able to do is just offer offer it as a unique offering through Lily Direct and not have to worry about all the Medicare stuff. But uh something something to think about. I know there's some stuff I got to catch up with here in the chat. If you're you're enjoying the conversation, let me know in the comments. But what did you come up with in
>> well um I don't know if I you know using chat GPT is all about giving it a great prompt and I don't know if I prompted it perfectly but um generally it's saying no Medicare coverage policy would not be a legitimate uh or direct reason for the FDA to remove it and that they're legally not allowed to um remove or keep a warning in order to influence Medicare coverage, private insurance reimbursement or federal spending.
Ask if there's additional liability for a pharmaceutical company if their drug contains that warning. Um, while Ann's looking that up, I want to check out Linda's question here. Thanks for everything you do. She says, "I saw on or read somewhere that Zep boundar as effective as ompic for future cardiac events."
Could be. It could be for future cardiac events. Um, one of the things that we've seen in the select trials for semiglutide that we have not seen with tracepatide is that the cardiac cardiac protective benefits in in patients with heart failure with preserved ejection fraction uh is that regardless of the dose that you're on or regardless of the weight that you lose, you decrease your likelihood of a of a heart attack or stroke, a major cardiovascular event. We have not seen the same data from lily. In fact, we haven't seen that trespide even differentiates itself that much from truly dulaglutide in a head-to-head study. It showed that that tratide was non-inferior, but it didn't get the superior um stamp from the FDA on that clinical trial because it didn't meet those end points. So I maintain as a dude on the internet, not a doctor, not a researcher, but based upon what I've seen, we've seen clinical trial data that that shows that simaglletide has potentially something unique about it or GLP-1 receptor agonism because there's not very much GLP-1 in trace. Um, it's like a 6:1 ratio um of GIP to GLP-1. So it's not super strong on the GLP-1 front. Um, what we saw in a pre-clinical model with rodents was that rodents were given a a GLP-1 blocker and a GLP-1 agonist. Uh, and then they induced a major cardiovascular event, a heart attack. And what they found is the population of mice that received the GLP-1 agonist, uh, parasites on the cells of the heart opened up, which allowed blood flow to be restored to the damaged areas of the heart or the affected areas of the heart by the heart attack. Whereas the rodents that received the blocker uh that part of the heart remained closed and then they lost function of that part of their heart. And so the the working theory is that GLP1 receptor agonism because of the specific receptors on the heart actually has something uniquely cardiac protective that GIP may not. That said, GLP1 GIP combo and treaside is more effective at weight loss. So to the ends that losing weight affects um your cardioabolic health of course it could be shown to be better. I think both if you're taking either I think you're doing yourself a favor which one is better I think is is the ultimate question that we still need to to pan out in in clinical trials. So um I think that's a great question. Let's see. Anthony says, "My family physician and my orthopedic surgeon says the same thing about FDA and the big pharma."
Yeah. Um, but do we know the long-term effects of obesity? We do know the long-term effects of addiction. And you know what? There's certain trade-offs. I'm willing to accept that these meds do.
Yeah. I think that's what you have to weigh, right, Mike? Is you have to weigh, again, no pun intended, you have to weigh um what we do know about living with untreated obesity is that you just have a much higher morbidity rate. um you have a much higher chance of dying from things like cancer and stroke and heart attack than if you treat the disease of obesity. Um, so what the trade-offs are. I just am of the firm belief that we need to be aware of what those trade-offs are, right? We need to be informed of what those trade-offs. You can't make an informed decision unless you are informed. And my issue with the with this removing the suicidality warning is like what do we know about long-term data? Because long-term data comes from postmarketing data. And we haven't had terspetide in the obese population for longer than two years. So, you know, and how much of that population has been at the highest dose for an extended period of time?
>> Yeah. Is the harm outweighing the the more accessibility of not having that label on it? Because, you know, clinicians might be more hesitant to prescribe it if they know that you are already somebody who deals with that. But we also know that obesity is something that can greatly contribute to your mental health.
Yeah.
>> Issues. So,
>> for sure. And that's one of the things that we we talk about here is that most most people actually say that their mental health improved
>> improved. But again, I go my my only position isn't that it should stay or it should go. My my question and I think it's a reasonable question to ask is what harm is there in leaving it on?
>> Yeah. Yeah.
>> What harm is there in leaving it on there? Because we just the reality is with the GIP medication, we don't know. We have no data to show what happens after you're on the high dose for four years.
>> Yeah,
>> we don't have that. Trazepide came out uh for for obesity. Um, at least Zepbound came out for obesity in what the fall of 2023.
>> Um, so we haven't even had three years of that on the market for that population. And like I said, the the warning has not existed to my understanding has not existed on the on the diabetes version.
>> But
>> I just think these are things that we need to know before we go removing labels like that. I But again, I'm saying this as a pa patient and a lay person and an advocate, not a clinician who may be able to come on and be like, you know, Dave, this is why we this is why we do that.
>> Same. But I would also just point out that, you know, removing the warning doesn't mean that mental health is irrelevant or that your clinician shouldn't be screening for it and that individual patients won't have issues. But there's one nuance in the languaging that's out there about it is the drug itself does not show a casual suicidality risk at the population level. That distinction is critical because it's it's often kind of lost in the mix that just because it's not widely happening doesn't mean it can't happen.
>> So,
>> just the nuance that gets lost off
>> like you can't watch a it doesn't feel like I can watch a single pharmaceutical ad on TV that doesn't say um consult your doctor if you're having
>> I heard a weird one the other day. I wish I could remember what it was.
>> Oh yeah, I heard I heard a crazy one. So, uh, shield thine eyes or cover thine ears if there are children in the room,
>> but the uh the warning was and it was for a really innocuous drug, right? I don't think it was a diabetes drug. It was like
>> consult your doctor if you have an inject an infection in your paranium. the the
>> no this is different
>> area between the genitals and the anus.
>> Oh,
>> and I was like
>> I think I have infection there. Like this is a this is a allergy pill.
>> Like I'm not sure I want that. I think I'll take the sneezing.
>> Yeah. Yeah.
>> Um, my goodness.
>> Another one.
>> You're welcome for that.
>> Another one that I heard was something about um I'm going to forget the language, but it's like allergy. Um, what you know when people need an EpiPen they're having a certain type of allergic reaction uh anaphylaxis anaphilaxis and it was saying that this this allergy medication can cause anaphilaxis so don't take it if you
>> you know could have anaphilaxis and then it treats anaphilaxis. That's like the main point of the drug. And I was like man there's got to be some crazy nuance and detail under this quick disclaimer but it's so confusing. I'd love to to have like a SNL sketch of like the lawyers talking about this in a boardroom. Okay, here's another one I heard the other day. So, um this was consult your doctor if you have certain fungal infections. I'm like define certain like like or if you've ever been to a place where certain fungal infections exist. I'm like what does that even mean? How's somebody supposed to make any sort of rational medical decision?
>> I know. It's like broad but specific. It's not It's like is that legal ease?
>> Like I feel like now I just need to like mention it when I sit down at the doctor. Like I may have had certain fungal infections.
>> It's like when Michael Scott on the office said I'll give them general specifics later.
>> General specifics. It's exactly what it feels like. Um, so anyways, yeah, that's that's all um kind of a a topic worth worth discussing. I'm curious what y'all
>> have to uh have to say about that. What else you have uh for us in the notes in terms of like what you thought might be interesting?
>> I caught my eye caught an article about um beriatric surgery and GLP1 uh weight loss over time. Um, let's see, make sure I've got my notes in front of me. was it was a study a single center retrospective cohort study and kind of the big headline was reshape fat and lean tissue differently over time. Um, and it looked like it uh was leaning towards the outcomes of beriatric surgery. Have you heard anything about this?
Um,
>> what was the last thing that you said?
>> Uh just that well let me see here. Fat fat mass reduction and lean tissue. Um, so there was a difference between the absolute loss of fat-free mass was larger in surgery group though the relative body composition shifts still favored surgical overall.
>> Yeah, we're definitely not there in terms of of the medications eclipsing beriatric surgery in terms of results and long-term outcomes. I think that reatride is going to get us closer there. Uh, because reatride is showing that it it might get up to that like 30% weight loss number. But again, that's um that is weight loss that is typically um very rapid. Um, I mean, well, we're talking about I can't remember what the study was.
>> Big tradeoffs still.
>> I mean, the beriatric surgery weight loss is is quicker, too. But I do wonder how much of that is the I think that patients get a lot more handholding when they have beriatric surgery. There's a lot more recovery. There's a lot more follow-up visits. That makes a lot.
>> I mean, so much of the so much of these medications are people are taking them and they're just doing a once weekly check-in. And as long as the scale is dropping, then it's like, hey, that's what we're going for. But ultimately, that's one of the things that we talk about here at on the pen is how one of the coolest thing that's happening in obesity medicine is that we're actually moving towards these conversations of okay, the the medicines are there. Um, when reatuit comes out, we're going to be so close to being there in terms of like you can get surgery level results out of a out of an injection.
>> Yeah.
>> But in terms of weight loss, just sheer percentage body mass lost. But but the conversation is starting to shift to how do we get that weight down and then not only get to a goal weight but get to a goal weight with a higher fat to muscle, you know, ratio. Like how how do you improve your muscle mass,
>> especially in women because it's always lower in women.
>> Mhm. And so I think that's the exciting thing is that you're seeing um some of this conversation start to um shift in terms of of not just the quantity of weight loss but the quality of weight loss.
>> Yeah.
>> And and so beriatric surgery seems to have more durable outcomes, more long-term. But I think there's a lot of folks in the community who are actually using GLP-1 medications to maintain their weight loss that they had with the surgery. And so
>> is it being prescribed more GLP1s as a companion product to beriatric surgery?
>> Uh, it's yeah, kind of I mean, so one of the things about beriatric surgery is a lot of folks who have beriatric surgery have to lose a certain amount of weight before they can have the surgery. to be able to go under the knife and be safe as possible. That a lot of times doctors won't operate on you until you're under x amount of weight,
>> etc., etc. So, one of the things that they're being used for is to help get that patient down to that weight so that they can then have the metabolic surgery.
>> And then there's the other end of it where doctors are using it for patients who are having regain after beriatric surgery or just for maintenance.
>> Um,
>> maintenance.
>> What's that? I was wondering about
That being a maintenance thing because the people I know personally that have had bariatric, that's always the the struggle is they'll lose weight and then the regain. But some of the data is showing that it it's it seems that overall people do maintain pretty well.
Yeah. Yeah. I think we'll continue to kind of see that kind of data pour out. Um, I think for two two reasons. I think the bariatric surgery industry is kind of like probably in a bit of a panic over GLP-1.
Oh, I bet.
Um, but they also have to be in a bit of a panic because you have other companies like Fractal Health, who we've had Har, the CEO from from Fractal, over on on the pen a couple times over the last couple years, and they've got a quick 45-minute outpatient endoscopic procedure. Yeah. It doesn't cut you up or anything, but it's just real quick and it resets the cells in your gut and and then you're signaling proper properly and you can maintain, you know, the weight loss with the GLP-1 without the GLP-1. Yeah.
And so that's a that's an exciting thing to ponder as well.
Yeah, definitely.
Fresh eclecticism never made it down to goal weight after sleeve surgery and gained more than half of her weight back. She got down past goal on Zebound, has been maintaining for a year and a half. That's that's awesome. is a perfect example of of as you said, kind of like a companion product to to bariatric surgery. I think the smart bariatric surgeons, like one of my favorite guests that we've ever had on on the pen is Dr. Daniel Rosen. He's like a renowned bariatric surgeon out of New York City.
Yeah.
And just a hoot to hang out with. Just a fun guy. Um, a fun guy. We're back on the on the certain fungal infections talk. Um, one of the cool things, one of the lesser known facts about Dr. Daniel Rosen is his wife was on Real World. You remember that show in high school?
Yes. I mean, we weren't allowed to watch MTV, but we knew about the show.
We did. Yeah. Um, so fun fact about Daniel Rosen, but he's, you know, he's one of those bariatric surgeons who has just full-throated, embraced GLP-1s and and I think it's smart because he's passionate. I mean, that that's sort of where you can tell somebody's passion is like his passion is to help people with obesity. So he knows that there are tools that he has in his bariatric surgeon belt, that aren't addressed in the same way that GLP-1s addressed something, and so he just views it as another tool and hasn't been intimidated by it. At the end of the day, I think there's always going to be a need for some level of of that, kind of durable metabolic surgery. Uh, whether it be patient accessibility to these drugs, cost prohibitive nature of these drugs. I think the stronger these drugs get and the better they get. So, one of the drugs that um Lily is looking at is a drug called bagrammab. So bagrammab is a monoclonal antibody um that is a myostatin pathway inhibitor. It was actually first designed for patients, I believe, like the geriatric, cancer population to basically help them through chemo not waste away from a muscle standpoint. So, so they came up with bag bagrammab, which is a monoclonal antibody, uh, myostatin pathway inhibitor, and it's a biologic drug that can be combined, they're finding, can be combined with a GLP-1. So while the weight is going down and the fat mass is going down, the the lean muscle mass is going up.
Oh, wow.
So, it doesn't act on like appetite or hormones like GLP-1, but when you combine it with the GLP-1, the GLP-1 does that. And then this increases muscle mass and increases um, you know, at the end of the day, again, quality of weight loss, not just quantity of weight loss.
That's exciting.
The interesting thing about Magab, so so Lily, Eli, Lily, the maker of Zetbound and Mounjaro, bought the company. I think it was Versanis. I could be forgetting, it's been like three years since I made the video. But they bought the company that had beagrammab. At the time, Versanis started studying beamagrammab with semaglutide, Novo's drug. So Lily finished that trial out. It's funny, they finished the trial with a competitor's drug, but their plan would be to combine bagrammab with tirzepatide ultimately, or even retatride. So that
Okay, sure.
And and imagine this thing combined with retatride. That's that's crazy because retatride takes you down 30%. So imagine me losing. So I'm like at 270 lbs, right? I lose 30% of my body weight. So 70 lbs roughly, but not only am I down 70 lbs, I'm like jacked at the end of it. Like that's that's a crazy thought. So the the ability to um sort of like rewrite the script on somebody's body composition is like a wild thought.
I'm also thinking about when one drug company needs to order a bunch of drugs from the competitor. Like how does that go?
Yeah, right. They probably use compound.
Yeah, bro.
Um, people care a lot about total weight loss, not the fat muscle ratio. My PCP said most of the weight loss over percentage will be muscle, excluding the first month of course. I think what the clinical trials show is semaglutide is the worst offender. Semaglutide in the clinical trials, the the total uh lean mass loss was about 30% of the total weight loss. That's as high as I've seen. Tirzepatide's down in the low 20s, I think. Um, but still, you know, your point is well served. Like one of these days we we are turning the conversation to quality of weight loss, which is part of why we started GLP Medicare, GLP1medicare.com and our companion uh YouTube channel, uh, is because we're concerned about that as this rolls out to Medicare patients. Um, it's extremely important in that population that we preserve muscle mass. Like like I told you, Maggrammab, I think, was originally developed for the geriatric population who had cancer treatment.
Yeah. Right. And so I think it's extremely important for that population as we roll out to 50 million people later this year, the ability to get these drugs that they're not just losing their because this is a pilot program. So let's say after the Trump administration, they scrap this pilot program and they don't pass the Treat and Reduce Obesity Act. All these, you know, we got all these skinny older folks walking around and then they lose their drug coverage and now they they regain because that's what the clinical trials show is what happens. And then when they regain, they lost 30% of their muscle mass on the way down, but when they're regaining, they're regaining all fat.
Yeah.
So, they end up in a worse position to begin with, which is why it's going to be so important for that population to focus on preserving their muscle mass along the way, eating protein, prioritizing protein, resistance training, and all those things, which is part of the reason that we bought this building, so that we can do some of those resistance training stuff and cooking and all that stuff to help uh folks along the way. So, if you haven't followed, make sure you jump over and follow GLP1 Medicare uh over here on YouTube. And we'll have a website up within probably the next couple of weeks at GLP1medicare.com. Uh, so, please please uh make sure you check that out. Uh, Dana says, "I saw your post about Tom Brady endorsing GLP-1. Was happy to see this as I feel it legitimizes GLPs. Is his company only prescribing the oral version?"
So, my understanding and Ann, you you read I think a little bit more about this than I did. Um, so Tom Brady's company that he's like the chief medical officer or chief wellness officer, I think it was EMed. Um, I think they're more about working with insurance companies and employers, aren't they? Or employers specifically to develop programs. What I didn't like about it was it came with like strings attached in terms of like, you know, um, requiring patients to jump through hoops to get their medicine. I don't like that at all. Um, and and I like it's not that I mind Tom Brady or any celebrity uh endorsing anything. I love the Serena Williams thing. I love the Oprah thing. Um, I love it because I think it it takes helps to reduce the stigma to some extent. This Tom Brady thing does too. It's just that I can identify with Serena's story when you feel like you're doing everything right and the scale doesn't move right. I can identify with Oprah's story where you tried everything, everything there was in the book. You you know you you have a public, all the money in the world of it, and she still struggles.
Yeah. And and Oprah's like the textbook example of like there's no better example of like not only does she have everything at her disposal if she would so choose, but she's built an entire empire. She's like the queen of the freaking universe, as Michael Scott would say. And uh and so you can't say Oprah lacks willpower.
Yeah.
The discipline that it takes to build an empire like that is something that you, me, and everybody within the sound of my voice will never know.
Yeah.
Oprah knows it, but very few people on the planet know the kind type of discipline it takes to build what she has built.
Yes. And so she doesn't lack willpower. Her she wasn't overweight because of a lack of willpower. And so she's the textbook example for that. So when she finds a drug and she's like, I mean, she looks great. She I mean, I know we're not supposed to.
71.
Yeah, she does not look 71.
Yeah, she's gorgeous. And I mean, it's just kind of been I think an incredible story to watch uh unfold. Um, I'm trying to get to any other questions that are in the chat before we wrap up here in a few minutes. Robert said, "Are the trials really overstating the fat loss results because they're quoting the extreme dosage users?" That's not the real world. Are the trials really overstating the fat loss results?
Um, okay. So, I think I understand what your question is. Um, yes. Yes. I mean, every real world study shows that the the weight loss in the real world is not getting to the level that we're seeing averages in postmarketing data. Postmarketing data meaning they they vacuum up all the data from all the electronic medical records. They anonymize that data and then they go, "Okay, here's all the people on this medicine and here's what their weight did over the x amount of weeks that they were on the drug." When they look at that data, the weight loss does not typically affect the the clinical trials. But that said, the clinical trials are an average. There's people in this chat. So the average weight loss for tepetide was 22% over 72 weeks. Uh, 22, 23% I can't remember. Somewhere in there, right? How many of you in the comments of this video have lost a higher percentage than that? So, drop it in the comments. If you're like in the 30s, 30% or more of of body weight loss, drop that in the comments. Conversely, if you've lost less than 15% of your body weight, put that in the comments. It's such a spectrum. So, Michelle Khan has lost 53% of her body weight.
Wow.
That's insane. Um, and so Darian's in the house. Good to see you, Darham. Hey, I Daram, I sent you a Substack message a couple weeks ago. Uh, check your Substack messages. Uh, good to see you here, buddy. Glad glad that you're able to jump in for a few minutes. Uh, Jay Neb has lost 30.7% of her body weight. Debbie has lost 36% of her body weight on Tirzepatide. 46%. Uh, MVO has lost on tepetide. Uh, 31. George has lost. Katie's lost 30%. Uh, these are amazing incredible numbers. Um, so when we talk about the postmarketing data, we're talking about an aggregation of numbers, but anecdotally, you're always able to find people who beat the clinical trial data numbers and people like me who underperform the clinical trial data numbers. And there's a thousand factors, but one of the things that I really appreciated um yesterday we shared there's a an interview that Oprah did with Serena Williams uh over on the Oprah podcast and they were talking about, you know, the reason that we need different drugs, stronger drugs, is because there isn't just one kind of obesity. There are many kinds of obesity. There is a spectrum of metabolic disease. And so some people you have you're way over here, you know, just a little bit of metabolic disease and over here you got people who are completely jacked up, you know, type two diabetes, fatty liver or liver disease, um, all sorts of, you know, things going haywire that that the drugs have to address before they're ever going to address the weight on a person's body. So one of the things my doctor said was, you don't get healthy and then lose weight, or you don't get you don't lose weight and then get healthy. You get healthy and then your body loses weight.
I like that.
48% body weight, 19% body weight, 38% body weight. Uh, Darian says down 9 to 10% on Mounjaro. Uh, Darian, what is the period of time on that, buddy? Uh, just amazing numbers there. I appreciate everybody sharing that in the comments. Well, we go live for an hour on every Monday, Wednesday, Friday here on YouTube. If you enjoyed this conversation, let me know in the comments of this video. Um, Incret Science, I see you over there too. I see some some comments from you. I hope you're doing well today. Um, I hope that you'll hit the subscribe button. Uh, if you enjoyed it, I hope you'll hit the thumbs up button. So, we have one person at 24%. I think that was the closest that we've seen to the 23% Tirzepatide number, right? Um, so very few people actually hit that number. Most people are a spectrum. Um, and the number sort of falls in the middle, right? 62%. That's incredible. Wow.
Is there anything left, Turbo Gal?
That's amazing. That's amazing. What an incredible story. Um, but, uh, yeah, every Monday, Wednesday, Friday, we go live. Uh, my ask of you all about 99 weeks. Uh, it's crazy that it's that you're saying it was March of 2024 and that you're saying that that was 99 weeks ago. How fast time
Oh, man.
flies. Woody, what's up, buddy?
A meme that was like, "COVID wasn't three years ago, it was seven years ago."
I was like, what?
Yeah, that's wild.
It's so wild.
Um, wasn't it six years ago?
I mean, I guess like the um the beginning of it and maybe it said six. Maybe.
Well, it depends on where you were in the world, I guess. Um, so Monday, Wednesday, Friday, 12:00 p.m. Eastern. We're live here every Monday, Wednesday, Friday. So, hope you'll hit subscribe on the YouTubes. If you are into getting a weekly rundown on your drive to work, please download our podcast wherever you get podcasts. Just type in on the pen, GLP1 News, into your podcast platform of choice. And while you're there, if you just do us a favor, leave us a five-star rating and review. It helps train the Al Gore rhythm to push this out. And and one of the coolest things that it does is it puts us on this list. So when we when you go into your podcast app and you click on a category, there's all these categories here. I got to cover my face here. See that? Medicine's a category. I'm going to tap on that category and then it shows all the popular shows for medicine, right? Sorry, I have to cover my face. So these are the popular ones. If you click on that and you scroll down a little ways, you're going to see that. See how we scroll? And that's on the main Apple podcast page. The only reason that we're there is because you all take a moment to go in there and give us a five-star rating and review and then you download the podcast. Those are the two things that affect our ability to show up there. The higher we go, the more people we can reach. I just talked to you yesterday about how the amazing thing about Oprah's story is that with one video, Oprah can put it out and she hits 50 million people. We hit 16 million last year. We hit 16 million people last year with our message. Oprah with one video hits, you know, five times that amount of people. That's the power of this getting into the mainstream. And so we've been working and we were and I said, like, it's crazy to hear Oprah saying the same things we've been saying on TikTok lives and YouTube lives for three years.
Food noise gone, uh, slow responder, super responder, all these things we have been talking about and some of the phrases that even our community gave names to. To hear Oprah talking about that is amazing. And so um, we want to continue to grow what we're doing here because we believe what we're doing is important. We've given our life's work to building this here at On the Pen. So, I hope that you'll just take a moment, download the podcast, um, give it a bump with a five-star review. We're at 388 reviews right now. I'd love to be at 400 when I wake up tomorrow. So, if you just go to Apple Podcast, find the podcast, scroll down, hit five stars, that's helps us out tremendously. So, thank you for doing that. Thank you all for being the best part of what you do. Gan, you got anything before we go?
No. Uh, I really don't. I'm just excited to be here, guys. It's It's fun.
Yeah. Uh, great conversation today. Thank you for for putting together those questions. Uh, we'll do it again on Friday at 12:00 p.m. Eastern. I hope you'll join us. Hit that like, hit that bell, hit that sub. Until next time, we will catch you on the next one.