Retatrutide Appetite Supressionn And Increased Fat Loss, Endogenous GLP-1, GIP, & Glucagon

追加: 2026-05-09

[00:00:00]If the situation is favorable for lipolysis, then activating the GLP-1 receptors on adipose tissue actually helps with the fatty acid removal out of adipose tissue, stimulating overall fat loss.

[00:00:16]Vigorous Steve here. Before we get into the retatrutide deep dive, please understand that all studies performed on retatrutides were published from September 2022 onwards. And that means none of them are available as full publications through Science Hub.

[00:00:31]Science Hub goes back regarding their full publications up until 2021, give or take. And I honestly felt a little bit handicapped preparing for this retatrutide deep dive because normally I have access to all full publications through Science Hub, so I can read everything I want to know on a particular compound that I make a deep dive on. For this deep dive, I didn't purchase a single study as the total value of studies locked behind the paywall was $1,645, give or take. Luckily, I was able to read a few of these publications for free through my friends who have the right credentials to access these studies you otherwise have to pay for.

[00:01:06]Now, obviously, I can't show those studies on screen. I'm sure you guys understand. And if you want me to do additional research, send $1,645 and I'll gladly pay for all of those studies and review the entire um deep dive all over again to see if there's any additional information that I left out because again, otherwise I would have to spend a buttload of my own money. And I feel that the time investment that took place regarding the review of the studies that were available for free was already extensive enough and most of the studies which are published for free contain all of the relevant information that you would like to know about the clinical trials which are otherwise locked behind the paywall or some of the other studies which are locked behind the paywall, right? A lot of the conclusions from those studies behind the paywall are copied into the studies that are available for free. So, I think I was thorough enough and it doesn't warrant throwing uh $645 into this deep dive to purchase all the studies and then make a follow-up addendum video for you guys. And you guys really want to see it, then we'll start a GoFundMe. Then well, I'll gladly do it all over again.

[00:02:06]Retatrutide, also known as LY3437942, which is the name it generally goes by in the clinical trials. Don't you worry, I've linked all of them down below in the YouTube description section and the comment section in case you want to give them a read for yourself. Retatrutide is a novel triple action glucagon-like peptide-1 receptor agonist as well as glucose-dependent insulinotropic polypeptide receptor or uh also known as gastric inhibitory polypeptide receptor agonist and glucagon receptor agonist peptide medication, which is currently undergoing clinical trials for potential treatment in obesity and type 2 diabetes mellitus. It was originally developed by Eli Lilly. I'm sure their stock will get a nice boost in overall total valuation a couple years from now when retatrutide is finally introduced into the medical field as an FDA-approved medication. But for now, the only way to get retatrutide are through the Chinese generic peptide resellers. And that means you can try retatrutide well before it hits the market. And um you can probably get it a lot cheaper compared to liraglutide, dulaglutide, semaglutide, tirzepatide, exenatide, or some of the other glucagon-like peptide-1 receptor agonist type medications. And it seems that everybody in the fitness community already got the memo and made the pivot to retatrutide after a couple years of self-experimentation with either liraglutide, dulaglutide, semaglutide, or tirzepatide, which became increasingly popular because it's a dual action GLP-1 and GIP receptor agonist.

[00:03:36]So again, whether you experiment with pharmaceutical lira, dula, sema, or tirzepatide or Chinese generic peptides, um nowadays everybody seems to make the pivot to retatrutide and they said they get a much more pronounced effect for the same amount of appetite suppression because you get additional fat loss through this glucose-dependent insulinotropic polypeptide receptor agonism and glucagon receptor agonism.

[00:04:00]For now, I'm going to have to conclude that retatrutide is the superior compound in this class of medications until that is until NA93 hits the market, which is a quadruple action GLP-1, GIP, glucagon, and IGF-1 receptor agonist. It probably goes by the name bilaglutide. As soon as NA931 bilaglutide will hit the markets, you know I'll make a deep dive on it. And then everybody can pivot from retatrutide to bilaglutide for all the right reasons, uh fingers crossed, potentially. So, let's start this deep dive off with a little bit of a visualization on how these peptide hormones look and how they interact with their relevant receptors. This study was performed by Lee et al. published on July 2024, so it's less than a year old, titled structural insights into the triple agonism of GLP-1 receptor, GIP receptor, and glucagon receptor manifested by retatrutide. You see here the structural similarities between the various incretin medications and how retatrutide interacts with the glucagon-like peptide-1 receptor, glucose-dependent insulinotropic receptor, and glucagon receptors. As you can see, it can bind to all three of these receptors, albeit with different affinities and strengths compared to endogenously produced GLP-1, GIP, or glucagon. From an endogenously produced hormone perspective, GLP-1 enhances glucose-dependent insulin secretion from the beta cells of the pancreas, contributing to glucose homeostasis in the bloodstream. GLP-1 also inhibits glucagon secretion, reducing hepatic gluconeogenesis, and keeping blood glucose levels in range through this pathway. GLP-1 slows gastric emptying and inhibits gastric motility, promoting satiation and reducing overall food intake. And GLP-1 prevents beta cell apoptosis, promotes neurogenesis, and replenishes insulin stores. GIP also stimulates insulin secretion. Unlike GLP-1, GIP actually contributes to glucagon secretion. GIP interacts with insulin to increase lipoprotein lipase activity, contributing to the breakdown of triglycerides in the bloodstream and lipogenesis in adipose tissue, meaning that if you stimulate the GIP receptor on adipose tissue and fat is going into adipose tissue, that you're literally telling it to be stored. Now, if serum insulin and serum glucagon are favorable and serum glucose levels and serum triglyceride levels are favorable and you stimulate the adipose tissue with beta-2 adrenergic receptors or hormone-sensitive lipase being increased by growth hormone or another lipolytic agent, if the situation is favorable for lipolysis, then activating the GLP-1 receptors on adipose tissue actually helps with the fatty acid removal out of adipose tissue, stimulating overall fat loss. GIP promotes growth and survival of beta cells in the pancreas. And experimental studies suggest that GIP may have an effect on bone metabolism.

[00:07:03]And when it comes to glucagon, it mediates hepatic glucose production coming either from glycogenolysis or gluconeogenesis.

[00:07:10]With glycogenolysis, glucagon helps with the breakdown of stored glycogen within the liver and thus keeping serum glucose levels in range throughout the night predominantly when serum insulin levels are low and a dietary carbohydrate intake is basically nonexistent because you're not eating while you're sleeping.

[00:07:28]And with a gluconeogenesis, that's the breakdown of amino acids or glycerol into glucose, keeping serum glucose levels in range that way. And whether the protein is coming from um skeletal muscle leaking out of it during strenuous workouts, especially when cortisol starts to go up, then you get some gluconeogenesis. Or this dietary protein is being consumed, obviously, converting into glucose through gluconeogenesis. Or glycerol coming from adipose tissue, which is stored as the backbone alongside three triglyceride molecules. When glucagon stimulates the glucagon receptors in adipose tissue, it causes lipolysis. So, these three triglyceride molecules and one backbone in form of glycerol is being released into the bloodstream. You can um burn the triglycerides away in the mitochondria. And this glycerol backbone gets converted into glucose through gluconeogenesis, which glucagon stimulates in the liver. So, you get lipolysis, glucose homeostasis, and the preventing blood glucose levels from dropping too severely during fasting, in between meals, or fasting throughout the night. So, by activating all three of these receptors, albeit with different levels of affinity, retatrutide promotes satiation by reducing gastric emptying, reducing your appetite overall, and taking away the food noise, so you can have a better control over your diet and overall caloric intake. It promotes glucose homeostasis in the bloodstream, regulating blood glucose levels by promoting or contributing to the secretion of insulin and glucagon. And in a caloric deficit, which is very easy on retatrutide as your caloric intake comes down, you can control your diet a lot better on retatrutide. As the calories come down, it actually promotes lipolysis through the glucagon and GIP receptor, and thus your fat loss journey is significantly easier. And this makes retatrutide almost the ideal fat loss agent. And compounds like clenbuterol or sibutramine or tesofensine or other stimulatory fat burning agents are probably not required.