Episode 256 – How Peptides Work, Benefits, and FDA-Approved vs Off-Label Use Explained

Dr. Deb Muth What if the reason you’re not healing isn’t that you need another diagnosis? 0:08 It’s that your cells aren’t receiving the right signals. Because the body doesn’t run on diagnosis, it runs on 0:16 communication. And peptides are one of the most powerful, most misunderstood 0:21 tools we have for cellular signaling, immune balance, tissue repair, gut 0:27 lining support, metabolic control, brain signaling, sleep cycles, and even sexual 0:35 wellness. Today, I’m going to do what most people won’t. Define peptides in 0:41 plain English for you. break them into categories by what they’re best at and 0:47 tell you which ones are FDA approved on the list and which ones are commonly 0:53 used off label or investigational with the evidence that actually says these 1:00 work. This is going to be a powerful episode and if you’ve ever felt like you’re hearing hype without clarity, 1:07 this one’s for you. So, as usual, grab your cup of coffee or tea and settle in 1:13 as we talk about peptides that can fit into your healing journey. We’re going 1:19 to have a short word from our sponsor. You know, we got to do that. That’s how we stay on the air here. So, we will be 1:26 right back after this. Did you know sweating can literally heal your cells? 1:32I nfrared saunas don’t just relax you. They detox your body, balance hormones, 1:37 and boost mitochondrial energy. I’m obsessed with my health tech sauna. And 1:42 right now, you can save $500 with my code at healthtechalth.com/drmuthqen25. 1:54 All right, here we go, guys. I am excited to dive into peptides with you. 2:00 So understanding peptides is foundational, right? And I’ve been 2:06 studying peptides now for about nine years. Um, and I find that they are 2:13 incredible. Um, so I want to break down for you what peptides actually are, what 2:19 they do, and some of the top peptides that are available today, and how they 2:25 can be utilized. Because I think it’s really important. And I think it’s it’s there’s a lot of confusion out there about what these things actually are and 2:32 are they safe? Are they not? When do we use them? What’s the science behind them? So, we’re going to dive in and 2:38 we’re going to talk about all things peptides. So, let’s get ready here. Here we go. So, peptides are short chains of 2:45 amino acids and they typically range anywhere from 2 to 50 amino acids and 2:51 they’re linked by peptide bonds. So think of them as the superglue that holds the amino acids together. They sit 2:58 between the amino acids and they are full proteins in terms of their size and 3:04 their complex structure. And what makes peptides particularly interesting in 3:10 medicine is their role as signaling molecules. They’re essentially the 3:15 body’s text messages carrying specific instructions to cells and tissues. And 3:21 unlike our proteins which often serve as structural roles or act as enzymes, 3:28 peptides typically function as hormones, neurotransmitters and growth factors and 3:33 they bind to specific receptors on the cell’s surfaces or within the cells and 3:39 they trigger this effect. It’s like a cascade effect of a biochemical reaction 3:45 that ultimately changes the cellular behavior. So basically, it’s changing 3:50 the way the body’s cell structure acts. And this is why peptides can be so 3:56 incredibly powerful and therapeutic when you introduce the right peptide signal. 4:02 Now, you could theoretically redirect cellular processes toward healing, 4:07 towards metabolism, immune balance, tissue repair. Any of those things can 4:14 be manipulated to do a certain thing once we add the peptide. The challenge 4:19 in peptide medicine though lies in distinguishing between those peptides that have been rigorously studied, 4:26 proven safe and effective and approved by regulatory bodies like the FDA versus 4:31 those that exist in what we call the gray zone of a promising clinical data. 4:36 But they really lack human validation so far. And this distinction is critical because the presence of a plausible 4:43 mechanism does not guarantee safety or efficacy in living humans. So, this is 4:50 really important and we’re going to dive in and look at some of the research on all of these different peptides that are 4:56 available and I’m excited to say there’s some amazing peptides being studied right now that unfortunately are not 5:01 available. But I can’t wait to see them hit the market for us because it is going to be a gamecher as far as health 5:09 and longevity. So there is a quality control issue and there is a hidden 5:14 variable in peptide medicine with this and it’s one of the most underappreciated aspects of peptide 5:21 therapy particularly for non-FDA approved peptides. It’s quality control. 5:26 When we discuss pharmaceutical medicines, we take for granted that the pill contains what the label says. Not 5:32 always true depending on where it comes from. You guys, if you’ve heard my episodes before talk about how many of our medications are made in China and 5:41 have been contaminated with other things, you will realize that that is not always true. So, just because it has 5:48 the FDA stamp of approval on the medication, it still does not necessarily mean it’s safe and we still 5:54 need to do our homework on it. So, sorry for digressing on you guys, but you know, when we get a medication, we we 6:00 think that what the amount says is what is there, doesn’t have contaminants, it’s manufactured with good 6:06 manufacturing practices. You’ll see that listed as GMP on the bottle, and it’s been stored properly, it’s been 6:12 maintained stable, and with research peptides and compounded formulations, 6:17 none of this can be assumed. So, I will share a story with you. There was a gentleman that was purchasing these 6:24 peptides online from a research facility and um did not know that they were 6:30 coming from China and he was ordering a particular growth hormone peptide and 6:35 after a little while he had he had done fine for the few first few bottles. After a little while he started having 6:42 some complications. He started getting really irritable and angry and ragy and 6:47 he didn’t quite know what was going on. And so he decided to go get some testing done. He had some blood testing done and 6:53 his testosterone level was over 5,000. So for those of you who know what testosterone level should be for a guy, 7:00 they really shouldn’t be any higher than about 1,00200 would be absolute max that we’d want to see. Now he was taking 7:06 testosterone but not to that degree. And prior to adding this peptide, his 7:12 testosterone was very stable. What they ended up finding out was the peptide that he was getting, whoever was 7:18 manufacturing it added testosterone to the peptide. They felt like if if it had growth hormone, that was great, but if 7:25 it had growth hormone and tes testosterone, all the better. And he didn’t know that. And this is the 7:31 problem that we can have with peptides if you don’t source them properly. if you’re not working with somebody that 7:37 knows how to source them and can prove that they are what they say they are. Um, I’m sure there’s a whole bunch of 7:42 studies out there too of people getting these peptides and paying hundreds of thousands of dollars for them over their 7:48 lifetime and finding out they were nothing more than just sterile water. So, you really do need to be careful 7:53 with your quality control. Now, this kind of leads us right into the next topic that we’re going to talk about and that’s the manufacturing question, 8:00 right? The FDA approved peptides are manufactured in facilities subject to 8:05 the FDA inspection rules following our GMP regulations and these facilities 8:11 must validate their manufacturing process, demonstrate consistency batch to batch, test for purity and potency. 8:18 They need to test for bacterial endotoxins and sterility and they need to maintain detailed records. So, when a 8:25 pharmaceutical company submits a drug application, the FDA inspects the manufacturing facility as part of the 8:32 approval process. If you’re getting peptides from a different country, none of that is happening. And there are some 8:38 ways for us to determine if that is what you’re getting. Typically, the rule of thumb is if your peptides are coming 8:44 with a different colored top, every one of them has a different colored top. Those are typically being sourced out of 8:49 China. I wouldn’t say that’s 100% but that’s kind of the rule of thumb that people follow. So compoundingies these 8:56 are thearmacies that make our bio identical hormones. They can make medications in any dose or strength or 9:02 route. There are thousands of them in every not that not in every state but 9:08 there are thousands of them around the country right now. So these compoundingies are registered as 503A 9:15 facilities. They do traditional compounding for individual prescriptions, right? Like they can make 9:20 thyroid, they can make LDN, they can make estrogen. You can also have a 503b 9:27 facility, which is an outsourcing facility. And these companies produce larger batches of products. They’re they 9:34 have some oversight, but they’re less stringent than for FDA approved 9:40 manufacturers. And state boards of pharmacy regulate a 503A pharmacy. And 9:45 the FDA can inspect the 503b facility, but doesn’t preapprove any of their 9:52 compounding products. So, they can inspect it, but they don’t approve them. So, research chemicals and these 9:58 suppliers operate essentially with no oversight. They explicitly market products for research use only, not for 10:06 human consumption to avoid FDA regulation. If they put that on their 10:12 product, they don’t have to comply to what the FDA is saying. And there is no required manufacturing strategies or 10:19 standards, no required testing, no required sterility assurance, and no enforcement mechanisms if products are 10:26 mislabeled or contaminated. So basically, they don’t have the liability, but that doesn’t mean that 10:31 all of them are badies or bad suppliers. It just means they don’t have to comply 10:37 to the FDA rules. Now, there are many of these companies that I’ve seen and I’ve talked to that do do a lot of this. They 10:44 do test their product for sterility. They do test their product to make sure it is what it says it is. They don’t 10:51 have to, but they do. So, if you’re going to decide to use a company that 10:56 has research only, not for human consumption, at least ask for their 11:02 proof of testing so that you know that the product you’re getting is what it says it is and that it’s clean. Because 11:08 this is where we run into the problem is in purity. So in purity peptide 11:13 synthesis can produce not just the targeted peptide but also related 11:19 peptides with deletions, substitutions, truncations or truncations of amino 11:25 acids. Sorry. And this high performance liquid we call it uh chromatography can 11:30 separate these related impurities and quality and quantify the actual target 11:35 of the peptide content. So a certificate of analysis is what you want to ask these companies for. This shows the HPLC 11:44 the testing mechanism with greater than 95% or ideally 98% purity which 11:51 indicates a higher quality product. So this certificate of analysis can be fabricated may not represent the 11:57 specific batch being sold. It happens. We need to know not everybody is honest. Not everybody, you know, does what they 12:03 say and it does what’s right. But at least you at least they’re giving you something and you have some security. 12:10 and then choose a company that was referred to by someone else that has done some homework as well. In in 12:16 commercial research, there’s independent testing and they research peptides and this has been really shocking 12:23 variability that they’ve seen. Some products contain 50% or less of the 12:29 claimed peptide and some contained primarily degradation of the product or manufacturing impurities and some 12:36 contained bacterial endotoxins at levels that could cause fever and systemic 12:42 inflammation if it was truly injected. And I would also worry with some of those problems, you know, depending on 12:48 what impurity or bacterial endotoxin was there. If you’re using a product to boost your immune system and your immune 12:54 system is already compromised, these bacterial endotoxins can actually make you sicker instead of what you want it 13:02 to do, which is making you better. So, sterility is always an issue with anything that is manufactured, 13:08 especially things that we’re doing as an injection. Peptides are intended for injection. They must be sterile. They 13:16 must be kept safe. And pharmaceutical manufacturers conduct this sterility testing on every batch. 13:22 Compoundingarmacies should conduct sterility testing particularly for high-risisk compounded 13:28 sterile preparations and research chemical suppliers may or may not conduct any testing. So injecting 13:35 non-sterile material can cause local infections, abscesses at the injection 13:41 site and or if the bacteria enters the bloodstream could potentially be 13:46 life-threatening and you could have sepsis. Now, excuse me. We saw this 13:52 happen in a compounding pharmacy uh gosh, it’s probably been 10 years ago 13:57 now, I think. um they unfortunately had a strep uh contamination in their 14:03 product and they weren’t testing it. It was a large compounding pharmacy out of Florida and they were making products 14:08 that were being injected into the joints and um these people got very very sick 14:14 and some of them died and um some of them got very very injured by this uh 14:21 complication that happened. So it’s not like this doesn’t happen. It does, but it doesn’t happen often. And that’s what 14:28 we have to know about. And so, when we’re talking with you guys about storage and stability, it’s really 14:34 important to make sure you maintain your peptides well. So, many peptides are unstable at room temperature. They 14:41 require refrigeration or freezing. We tell everyone to make sure you’re refrigerating your peptides. That way, 14:48 there’s no question about it. when it stays cold um it prevents or slows down 14:54 the process of uh bacteria growing in it. So some of these peptides actually 14:59 degrade very rapidly in the solution and they must be reconstituted immediately before use and reconstitution of the 15:07 peptides really has limited stability often just days to weeks not months. So 15:13 improper storage, temperature, um changes during shipping or prolonged 15:19 storage of a reconstituted product can lead to degradation into inactivity or 15:25 potentially even a harmful breakdown of the product itself. So if you have a product that’s been sitting in your 15:30 refrigerator for a month or two months or 3 months or 6 months, just throw it away. It’s not going to be any good. 15:37 you’re not going to actually get the peptide and the uh potency that you’re looking for anyway out of it and the 15:44 potential of you introducing an endotoxin, a bacterial endotoxin is quite high at that point. So you just 15:50 really don’t want to take the risk, excuse me. So what practitioners, what 15:56 should we do and what should patients do? Well, for any peptide therapy, we 16:03 want to source our verification. know where the peptide product comes from. Is 16:08 it an FDA approved product? Is it a 503b compounding? A research chemical 16:14 supplier? Is there a certificate of analysis? Request and review this COA. 16:20 And you want it to show purity greater than 95% but ideally greater than 98%. 16:27 You want that identity be identity to be confirmed by mass spectromedy. Uh 16:33 sterility testing should be done. Bacterial endotoxin testing should be done. Batch number matching of the 16:39 product that you received should be done. Proper storage. You want to know that this has been refrigerated or 16:46 frozen as directed once it’s been mixed. Look at the expiration dates for reconstituting your peptides. Track that 16:53 reconstitution date and discarded accordingly like we just talked about. Monitor for your adverse effects. Even 17:01 with the perfect quality control, monitoring for adverse effects is essential with questionable quality and 17:08 vigilance is really critical here. I know it’s frustrating for a lot of patients when they have to get several 17:15 bottles and they only last a week or two. right here, you guys. This is why 17:21 they only last a short period of time because once they’re mixed, they start 17:26 to degrade and they won’t be good and you won’t get the benefit from it. So, 17:31 it’s really important with these research peptides specifically, practitioners should recognize that all 17:38 recommending products without quality assurance violates the fundamental medical principle of first do no harm. 17:45 If a patient is determined to use research peptides despite counseling, providing guidance on quality 17:52 verification, requesting those COAs, using pharmaceutical grade sources when available, proper testing, this all 17:59 reduces harm, but doesn’t constitute necessarily that recommendation. Now, 18:06 that being said, today it’s very difficult to find peptides by the compoundingies because of what the FDA 18:13 has done. So most of the peptides that are available to us have been labeled 18:18 not for human consumption, not because they’re not good products, but because 18:25 of what the FDA did. And this is how these companies have been able to 18:31 continue to provide peptides to the medical community. And if you know you 18:36 have a good company, then you’re, you know, you’re still taking the risk, right? But at the end of the day, the 18:42 reason they’re doing that is to protect themselves from the FDA, from liability. Um, so just kind of know that there is 18:50 some talk in the community with um Bobby Kennedy that this is going to change and 18:55 they are going to bring peptides back to the compounding pharmacies. Now, we don’t know which ones they’re going to 19:01 bring back. Uh, will it be all of them? Will it just be some of them? What’s going to happen here? Um, is it going to 19:07 go to the pharmaceutical companies like our GLP1s did? We don’t know what that’s going to look like quite yet. Um, but it 19:14 is coming and that is positive news. So, let’s talk now about FDA approved 19:21 peptide medications. So, this is the metabolic revolution, right? GLP1 19:28 and our dual increeting agonists. This is an exciting time. GLP-1s are amazing. 19:35 Um, a lot of people are skeptical, a lot of people love them, a lot of people hate them. Whichever side of the fence 19:42 that you’re on, I understand. But I want to talk about the science of it today 19:48 and what it actually means for people. So, the story of GLP1 glucagon like 19:54 peptide one represents one of the most significant advances in metabolic 19:59 medicine in the past several decades. GLP-1 is an accretin hormone. It’s 20:05 gutder derived peptide that potentiates insulin secretion in response to food 20:11 intake. And the body naturally produces GLP-1 in the intestinal L cells, but it 20:17 rapidly degraded by the enzyme DPP4 giving it a halflife of only about 2 20:24 minutes. So this rapid breakdown made in therapeutically impractical until 20:31 research was developed and modified the analoges that resist the enzyme degradation. So for those people who 20:39 never feel full when they’re eating, never feel satisfied when they’re done, this is because their body is either not 20:46 producing enough GLP1 or it’s not getting the signal right. And this is a 20:51 leptin issue. This is an insulin issue. It’s a GLP-1 issue. It’s a complicated 20:56 issue. This is not anything that the person is doing wrong. It’s what is happening to their body. And so GLP1s 21:03 have really revolutionized this. So one particular GLP-1 that we have is 21:09 semiglutide. And this GLP-1 agonist is what changed everything in the world of 21:16 metabolic medicine. Semiglutide is marketed as ompic for type 2 diabetes 21:23 and it’s marketed as WGOI for chronic weight management. It is a modified 21:29 GLP-1 analog with 95 or sorry 94% amino acid sequence uh homology to human 21:37 GLP-1. So it means that it’s it’s just like our own GLP-1 that we make. This 21:42 modification includes specific amino acid substitutions and the addition of C18 21:50 a fatty acid chain which allows the peptide to bind to albumin. Now this 21:56 albumin binding dramatically extends the half-life to approximately one week 22:01 enabling one weekly dosing which is a major advantage over the earlier GLP-1 22:07 agonists that require daily or twice daily injections. The mechanism by which 22:13 semiglutide works is multiaceted. At the pancreatin level, it binds to GLP-1 22:20 receptors on the pancreatic beta cells enhancing glucose depending sorry 22:27 enhancing glucose dependent insulin secretion. This glucose dependency is 22:33 crucial. It means the peptide only stimulates insulin release when blood glucose is elevated. This dramatically 22:41 reduces the hypoglycemic risk compared to insulin or even uh sulfuras. 22:47 Simultaneously semiglutide suppresses glucagon secretion from pancreatic alpha 22:53 cells further improving glycemic control. This is really amazing because 23:00 over the years when we’ve used insulin, which is also a peptide by the way, you 23:05 had to dose it just right because if you didn’t, you would produce so much insulin that it would crash the blood 23:12 sugar and then somebody would have too low of a blood sugar. They’d be hypoglycemic and they’d have to eat more 23:18 sugar and then they’d have to modify the insulin again and the person would be going up and down, up and down, up and 23:24 down all day long. And that created a lot of problems for people and so this 23:30 helps to stabilize that so it is not such an intense change. Now in the GI 23:36 tract semiglutide delays the gastric emptying particularly pronounced during 23:41 the initial weeks of therapy. This slowing of the gastric emptying contributes to the sensation of being 23:48 full and early satiety that patients often describe. However, this effect 23:54 tends to attend to weight over time as the body adapts through the appetite 24:00 suppressing effects generally persist through central mechanisms. So, when we 24:05 talk about what is actually happening, we’re slowing that digestive process down. That’s why people aren’t so 24:11 hungry. It’s why they’re not eating so much. This is why people can develop constipation with these products because 24:17 it’s slowing the body’s digestive tract down. Now some people will call this 24:22 gastroparesis. Um gastroparesis is actually different. 24:28 It is when we lose control over what’s happening in the in the colon like the 24:34 nerves and things like that just stop working. I have never seen that with the GLP1s that we prescribe in micro doing. 24:42 um it’s been documented. It can happen, but again it a lot of it is dosing and a 24:48 lot of it is staying on top of your client and what’s happening and what’s going on and what you’re doing and making sure that they do have good 24:54 motility still. So a lot of these things can be mitigated if you have problems 24:59 with them. Now one of the most profound effects of semiglutide occur in the 25:05 central nervous system. GLP-1 receptors are widely distributed in the brain 25:10 particularly in the hypothalamus and the brain stem area where we are involved in 25:15 appetite regulation. So when when wilding and colleagues published their 25:20 landmark step one trial in the New England Journal of Medicine in 2021, 25:25 they demonstrated that participants receiving 2.4 4 milligrams of semiglutide weekly achieved an average 25:32 weight loss of 14.9% of their body weight over 68 weeks. Now, I want you 25:39 guys to really understand this. We’re talking roughly 15% body weight loss 25:45 over a year, longer than a year. 52 weeks is a year, right? This is 68 25:50 weeks. So, it took longer for them to lose. We’re not talking about giving 25:55 somebody a dose to lose 15% of their body mass in a month or two. That that 26:01 is not healthy for any of us. That is not what we’re talking about doing here. Now, they compared this to placebo and 26:08 the placebo was only 2.4%. So, that is a significant difference. 26:14 And even beyond the numbers, patients reported something very qualitatively different, a reduction in what’s now 26:21 called food noise. Everybody knows what food noise is. We’ve talked about this long before GLP1. It’s that craving. 26:28 It’s that part of your brain that just keeps thinking about I want to eat something. You know, that was actually 26:34 reduced and they didn’t expect to see that happen. Now, this refers to the constant mental preoccupation with food, 26:42 the intrusive thoughts about eating, the difficulty in feeling satisfied. Semi-glutide appears to appears to 26:49 modulate reward pathways in the misolyic system reducing hedonic eating and food 26:57 cravings. Now there are also great cardiovascular effects of semiglutide 27:02 that extend beyond weight loss. Uh the sustained six and select trials 27:07 demonstrated significant reductions in major adverse cardiovascular events uh 27:14 mace in high-risisk populations. The select trial published in 2023 showed 27:20 that semiglutide reduced cardiovascular death, non-fatal myioardial inffection 27:25 and non-fatal stroke by 20% in adults with overweight or obesity and 27:31 established cardiovascular disease but without diabetes. So this suggests that 27:37 mechanisms beyond glucose control and weight loss possibly including 27:42 anti-inflammatory effects, improvements in endothelial function and favorable 27:47 changes to lipid profiles. Now I will tell you the clients that I work with that are on GLP1, 27:53 they will tell you that their inflammation has been significantly reduced. We are also seeing really 28:00 amazing results in lipid profiles. um part of its weight loss, but there is a 28:06 component to this that is lowering the triglyceride levels because it’s related to sugar and how the body’s processing 28:11 it. And we’re seeing better profiles, less need for statins as a result of 28:17 that. If if you want to listen to my episode on statins, I have one on that. Uh they are not my favorite medication. 28:24 I think it’s overprescribed and overused um and not really affecting or 28:29 addressing the problem. So these things can really be helpful. There’s also some 28:34 uh ramblings going on with GLP-1s saying that they may be able to help with 28:40 addiction in the future because of where they’re finding it affecting the brain and how it affects the food noise and 28:47 the cravings that we have for food and the addiction for food. Could it potentially help with other addictions 28:53 down the road? We’ll have to wait and see on that one. So semiglutide’s FDA prescribing information also includes a 29:00 box uh boxed warning about thyroid sea cell tumors. So in rodent studies 29:06 semiglutide caused dose dependent and treatment duration dependent sea cell 29:12 tumors at clinically relevant exposures. So while it’s unknown whether or not 29:17 semiglutide causes uh thyroid cancer tumors in humans and the rodent thyroid biology 29:26 differs significantly from humans, the drug is contraindicated in patients with a personal or family history of 29:33 medillary thyroid carcinoma or in patients with multiple endocrine neopl neoplasia syndrome type two. it is 29:42 uh contraindicated for safety effects with that. Um I have seen endocrinologists okay GLP1s to be used 29:50 in patients who’ve had other forms of thyroid cancer just not the meillary 29:55 thyroid cancer. So there is possibility there. Now the most common side effects 30:00 are gastrointestinal. It’s nausea affects about 20 to 44% of patients 30:06 depending on the formulation with diarrhea, vomiting, constipation, abdominal pain, and also frequently 30:13 reported in clinical trials. I see this in my clinic, too, especially dose dependent. Um, and it happens early on 30:20 when you’re first starting the medication, but seems to settle out over time. The one that I would add to this 30:26 that I don’t think they have on here is an increase in acid reflux. We also see that quite often uh especially in people 30:33 who suffer with acid reflux to begin with. Now these effects are typically most 30:40 pronounced during the escalation and they like I said often improve over time 30:45 but more serious but less common adverse effects include acute pancreatitis. 30:51 The medication needs to be discontinued immediately if this is confirmed. You can see some diabetic retinopathy 30:57 complications in patients with pre-existing retinopathy and acute kidney injury. Um, this usually happens 31:05 secondarily to dehydration from the GI effects. There are some gallbladder disease um that can occur and people who 31:13 have a sensitive gallbladder will describe uh discomfort with that. I’ve 31:18 even seen some people who’ve had their gallbladder out on GLP1s at the higher doses complain of similar pain that they 31:25 used to have when their gallbladder was in. So, really important to just kind of monitor these symptoms and work closely 31:32 with somebody that understands them and can be on top of them quite quickly if this happens. Excuse me. From an 31:39 integrative medicine perspective, semiglutide really represents a powerful tool, but it’s not a standalone 31:46 solution. Remember, the medication addresses one aspect of the metabolic dysfunction, the signaling systems 31:53 controlling appetite and glucose homeostasis, but it doesn’t address the root cause that led to the metabolic 32:00 disease in the first place. Patients who rely solely on the medication without addressing the ultrarocessed food 32:07 consumption, the ccadian disruptions, the chronic stress, the sleep apnea, or 32:12 underlying hormonal imbalances often experience weight regain when the medication is discontinued. 32:20 The drug is also not a substitute for addressing the emotional and psychological drivers of eating 32:26 behavior, including the unresolved trauma that may manifest as emotional eating. I think this is really important 32:33 because we don’t address the trauma issue enough with clients and we need to 32:38 be looking at that. There is a huge trauma effect out there these days that is I don’t want to say leading to or 32:45 causing but it is definitely contributing to chronic illness and it’s not being talked about enough. So we 32:52 really need to be talking about this and addressing this trauma aspect. Now the next GLP that one that I want to talk 32:59 about is trespathide. This is a dual agonist. It takes center stage. It is my 33:05 favorite GLP one. Trisepatide is marketed as Mangjaro for type 2 diabetes 33:11 and Zepbound for chronic weight management and it represents the next 33:16 evolution in increantbased therapy. This is a dual agonist a 39 amino acid 33:23 synthetic peptide structurally based on the human glucose dependent insulin tropic peptide so GIP sequence but 33:31 modified to activate both the GIP receptors and the GLP1 receptors. So the 33:37 addition of the GI GIP agonism to the GLP1 agonism appears to create this 33:46 synergistic effect that goes beyond simply adding the two mechanisms together. So the GIP like GLP-1 is an 33:55 increant hormone secreted by what is called the K cells in response to nutrient intake. It enhances glucose 34:02 dependent insulin secretion but it also effects on atapost tissue metabolism 34:09 potentially improving the insulin sensitivity in fat cells and influencing 34:14 how the body stores and metabolizes fat. So some research suggests that GIP may 34:20 also have effects on energy expenditure though this remains an area of 34:26 investigation. So basically what we’re saying is this drug may actually help 34:32 people who are insulin resistant or insulin sensitive, not just somebody who 34:38 has problems with glucose control. So, this is super exciting because it opens 34:43 up the door for all of these people for decades that we’ve been trying to manage with insulin resistance and trying to 34:50 prevent diabetes and honestly most of the time have been unsuccessful 34:56 unless you can keep your diet at 50 grams of carbs or less a day, which is extremely difficult. Um, and take some 35:04 supplements that may or may not work and or take some metformin that may or may not help. this drug actually really 35:11opens that up and helps in that capacity. So there was a clinical trial 35:17 called the surmount clinical trial which demonstrated that trespathide produces 35:22 even more substantial weight loss than semiglutide. In the surerount one trial published by uh J tree I might have said 35:31 that wrong. I apologize if I slaughtered your name and colleagues in the New York England Journal of Medicine in 2022. 35:38 Participants receiving the highest dose of trespide, which is 15 milligrams, achieved an average weight loss of 20.9% 35:47 of their body weight over 72 weeks, compared to 3.1% with placebo. This 35:54 level of weight loss approaches what’s typically only seen in beriatric surgery. So, this is amazing because if 36:02 this medication works and we don’t have to do beriatric surgery, stomach stapling basically, um, oh my gosh, it’s 36:11 amazing. There are so many complications and risks that go with stomach stapling and the different procedures that they 36:17 do these days. People don’t absorb their nutrients properly. They have to do liquid nutrients. It’s very complicated. 36:24 It’s very challenging. Many of these people gain their weight back. Um, and 36:30 this procedure is not fun to go through. So, if we could change that and change 36:35 the lives of people who’ve really been struggling, it is amazing. And I will tell you that I have seen this work. I 36:42 have seen people lose 100 150 pounds on these medications over a year or two 36:50 period of time. It is definitely slower than beriatric surgery on some standpoints, but that is okay. You don’t 36:56 want that rapid weight loss. It’s not good for you. It’s not healthy for you. It doesn’t look well. You know, we want 37:03 to do this safely and effectively in the best way that we can possibly do that for you. Now, the adverse effect profile 37:10 is similar to semiglutide. It’s dominated by gastrointestinal effects. 37:15 Nausea, diarrhea, decreased appetite, vomiting, constipation. These were all commonly reported in the surmount 37:22 trials. And like semiglutide, tricepide carries a blackbox warning regarding the 37:27 thyroid sea cell tumors based on the rodent data and it shares the same contra indications in patients with a 37:34 family history of thyroid cancer and men too. So the mechanism behind why 37:40 tepatide often produces more substantial weight loss than GLP-1. The agonism 37:45 alone remains under investigation, but it may relate to the complimentary effects on the different aspects of 37:51 energy homeostasis or to GIP’s effects on atapost tissue and potentially on 37:58 central central nervous system pathways that GLP1 alone doesn’t fully address. 38:03 Now patients often report even more profound reductions in food noise with tricepide compared to GLP1 and uh sorry 38:12 GLP1 the agonists through this is anecdotal and hasn’t been regularly 38:17 quantified in quality studies. So I’ve done both uh personally and in my 38:22 practice. I really like trespide better than semiglutide. For me I had too many side effects with semiglutide. uh I had 38:30 less side effects with trespathide. I also plateaued on semiglutide which I 38:35 didn’t really care for. And with Tresepide, I haven’t plateaued and I’ve been able 38:42 to lose about 25 pounds in um a year and a half and I’ve been able to maintain 38:49 that. Um and I continued to use it because I do have a strong family history of cardiovascular disease. And 38:56 if this could help me so that I don’t follow my family lineage with cardiovascular disease, I am all for 39:03 trying to do that. I’ve watched too many of my family members suffer from this. I’ve lost my dad at a very young age. I 39:09 lost my grandfather at a young age to it. All of their brothers to this. And I don’t want to be that same person. So 39:16 that is why I chose to do that. And I think it’s really important for us to take a look at that and understand that. 39:24 Now, I know this has been a really long podcast and I don’t typically do podcasts this long. I have a whole host 39:31 of information on additional peptides. So, I’m going to break this up for you 39:36 guys and I’m going to do another episode and we’re going to pick up where we left off here with these peptides so that we 39:43 can actually start to dive into different peptides as well. So, check 39:48 out my next podcast show when we’re going to dive into the peptides that 39:54 talk about sexual wellness, immune function, and all the other cool things 39:59 that we can do with peptides. So until then, remember to like, share, and 40:04 subscribe. It really helps us get out to other people and share our information, 40:10 and join us for our next episode as we continue the talk about peptides. 40:15 Welcome to Let’s Talk Wellness Now, where we bring expert insights directly to you. Please note that the views and 40:21 information shared by our guests are their own and do not necessarily reflect those of Let’s Talk Wellness Now, its 40:28 management, or our partners. Each affiliate, sponsor, and partner is an 40:34 independent entity with its own perspectives. Today’s content is provided forformational and educational 40:40 purposes only and should not be considered specific advice, whether financial, medical, or legal. While we 40:48 strive to present accurate and useful information, we cannot guarantee its completeness or relevance to your unique 40:56 circumstances. We encourage you to consult with a qualified professional to address your 41:01 individual needs. Your use of information from this broadcast is entirely at your own risk. By continuing 41:08 to listen, you agree to indemnify and hold Let’s Talk Wellness Now and its 41:14 associates harmless from any claims or damages arising from the use of this 41:20 content. We may update this disclaimer at any time and changes will take effect 41:26 immediately upon posting or broadcast. Thank you for tuning in. We hope you 41:31 find this episode both insightful and thought-provoking. Listener discretion 41:36 is advised.The post Episode 256 – How Peptides Work, Benefits, and FDA-Approved vs Off-Label Use Explained first appeared on Let's Talk Wellness Now.