Retatrutide: Understanding the mechanism of action
July 7. 2023
In June 2023, Eli Lilly pharmaceutical company released the latest results from a novel drug called retatrutide. While this drug is still in development, the unprecedented weight loss results from clinical trials have everyones’ eyes on it. Every individual trying to achieve weight loss wants to learn the retatrutide mechanism of action, how beneficial this medication is, and when it will be available.
Retatrutide has the potential to become one of the most efficient weight loss and type 2 diabetes medications. Type 2 diabetes mellitus drugs to treat high blood sugar levels have proven to have a bodyweight reduction side effect. You probably have heard about Weogvy or Ozempic weight loss. Retatrutide is on its way to becoming one of that type of medication – potentially the most efficient one.
Even though this novel drug has not been released yet, if you are on a weight loss journey, you will be interested in knowing more about it. In this article, our weight loss clinic in Chicago will unravel the retatrutide mechanism of action. So if you want to understand how this new drug works and how it can boost your weight loss efforts, continue reading.
What is retatrutide?
Retatrutide (LY-3437943) is a developing drug for treating obesity and type 2 diabetes mellitus. This active compound activates receptor agonists in our bodies that help with blood sugar control and body weight loss management. Just like Ozempic or Wegovy (semaglutide), retatrutide is a glucagon-like peptide-1 (GLP-1) agonist. And in the same way as Mounjaro, this new drug also acts as another hormone called glucose-dependent insulinotropic polypeptide (GIP). Both hormones combined do wonders in promoting weight loss. But retatrutide takes the game one step further; this drug also acts as a third hormone: glucagon.
If one or dual receptor agonist medicines are already effective, this triple-agonist, or triagonist, new molecular entity promises to deliver even greater results. That will be very helpful for individuals struggling with obesity or, for example, those who are not losing weight on Ozempic.
What are receptor agonists?
To understand the retatrutide mechanism of action, you must first know what receptor agonists are. Let’s start by quickly defining receptors; they are protein molecules present at the surface of our wells. These receptors receive signals from outside the cells; the signal can come from neurotransmitters, hormones, or drugs. These substances can bind to the receptors and pass information to our cells. When our cells receive the information, they activate and act. For example, appetite-related hormones, such as ghrelin or leptin hormones, stimulate our appetite or let our cells know we are full after a meal respectively. Without the receptors, our cells couldn’t receive that information.
Receptor agonists are drugs or chemical agents that work by binding to receptors in the cells and producing a response. These agonists can be natural or synthetic; hormones and neurotransmitters are examples of natural agonists. GLP-1 is a naturally occurring hormone, but it is synthetically manufactured for drugs such as Ozempic or Wegovy.
How do retatrutide receptor agonists work?
Different receptor agonists have different roles in our bodies, depending on which cell receptors they bind to. As mentioned, retatrutide activates three receptor agonists: GLP-1, GIP, and glucagon. To have a better understanding of retatrutide mechanism of action, you must learn a little about these receptor agonists. Here we will explain how each one works in our bodies and why they aid with weight loss:
Glucagon-like peptide-1 (GLP-1) is an intestinal peptide hormone our body produces after we eat. This hormone plays many roles, but it is mainly known for its part in regulating food intake and hunger. After we have a meal or a snack, our blood glucose levels start to rise. That is when our body releases GLP-1; this peptide stimulates insulin secretion from the pancreas.
Insulin is another crucial hormone our body produces; it allows glucose from our food intake to get into the cells. Our cells use glucose as their primary source of full to perform all vital functions. Insulin plays a crucial role in blood sugar control and weight gain. Without insulin, sugar can’t enter the cells; besides your body not absorbing nutrients, glucose would remain in the bloodstream, leading to high blood glucose levels. Your body stores the excess glucose as fat, which causes weight gain.
GLP-1 promotes insulin secretion from the pancreas and decreases glucose release from the liver. Apart from lowering blood sugar levels, GLP-1 also produces slow gastric emptying. Food will travel slower through your digestive system, remaining in your stomach for longer. That will make you full faster when you eat, and you will stay satisfied for longer as well. GLP-1 also targets your brain’s hunger center, decreasing your appetite. These two GLP-1 actions make you feel less hungry, like appetite suppressants, such as Phentermine for weight loss, do.
Glucose-dependent insulinotropic polypeptide
Just like GLP-1, glucose-dependent insulinotropic polypeptide (GIP) is part of a family of hormones known as incretins. Therefore, both peptide hormones act very similarly. This hormone is produced in the small intestine after we eat; it targets beta cells in the pancreas, making them release insulin. This effect helps lower blood sugar levels after food intake. After being released into our system, GIP doesn’t last very long; this hormone is broken down in about 7 minutes. GIP receptor agonist drugs, such as Mounjaro, help maintain higher levels of GIP in our bloodstream for longer. This hormone produces slow gastric emptying and appetite reduction. It targets the brain as well as your digestive system. That is why the stomach is one of the best place to inject Mounjaro for weight loss.
Glucagon is another hormone that plays a crucial role in blood sugar management. Just like GLP-1 and GIP, it is produced in the pancreas but by another type of cell known as alpha cells. Glucagon works towards blood glucose control and weight management in a totally inverse way compared to the previously mentioned hormones. When our blood sugar levels start to drop because we are not eating or we are sleeping, glucagon converts glycogen (the stored form of sugar) into glucose so our body can use it as fuel. Insulin and glucagon have opposite effects, but both work together to maintain normal sugar levels. While insulin converts sugar into glycogen, glucagon does the opposite.
How does glucagon help with weight loss? Our body stores excess glucose from the food we eat as glycogen and fat. When we go several hours without carbohydrate intake, glucagon will get to work to try to generate glucose. That can happen when we are sleeping, on a low-calorie diet, or practicing fasting benefits by hour. First, glucagon will break down glycogen, but after those stores are depleted, it will break down our fat stores to turn them into fuel.
Besides that, glucagon combined with GLP-1 and GIP created an increased energy expenditure. Your total energy expenditure is the number of calories you burn throughout the day – while performing any type of physical activity and the work your body does to perform vital functions such as breathing or digestion. Higher levels of energy expenditure mean your body will burn more fat.
What makes retatrutide stand out from other drugs?
Retatrutide may still be in development, but the results from clinical trials show how promising this new drug is for weight management. Retatrutide comes to raise the bar of this type of weight loss medication by delivering a larger percentage of body weight loss.
While on the highest dose of Wegovy (the weight loss version of Ozempic), individuals lose up to 15% of body weight in about 68 weeks. Mounjaro came to enhance the game by promoting 22% of body weight loss in around 72 weeks. In Eli Lilly’s latest clinical trials, retatrutide’s highest dose helped patients lose 24,2% body weight in only 48 weeks. Not only retatrutide promotes more significant weight loss, but it also does it in an incredibly shorter period of time; it beats how long does Ozempic take to work.
Another good news is that by the time the study was over, participants never reached a weight loss plateau. That means if individuals kept using the drug, they could have lost even more weight in the following weeks.
What makes retatrutide more efficient than other medications? The answer is this drug’s triple receptor agonist effect. GLP-1, GIP, and glucagon combined lead to more efficient weight loss.
Can I switch from Ozempic to retatrutide?
With retatrutide outstanding weight loss results from the trials, it is likely many people will want to change medications. The same happened when Mounjaro was launched. There are many reasons beyond effectivity why a person may decide to switch treatments. All these medications come with adverse effects, which can make it difficult for some patients to tolerate them. The most common side effects of Ozempic and Mounjaro include dizziness, nausea, vomiting, stomach upset, constipation, and diarrhea. Individuals are likely to develop these symptoms when their doctor increases the dosage or when they have their weekly shot. However, there are Mounjaro foods to avoid to manage the side effects. Retatrutide appears to cause the same mild side effects, and they are also only temporary.
While there is still not enough information about what the retatrutide weight loss program will be like, it will likely be similar to the Ozempic or Wegovy ones. That means that if you are uncomfortable or getting the expected results a few weeks into the treatment, you could try another drug. Retatrutide has a similar mechanism of action to Ozempic, so the transition should be smooth. Both drugs are applied weekly through subcutaneous injections as well. Nevertheless, just like when switching from Ozempic to Mounjaro, you must consult with your healthcare prover before switching from your current medication to retatrutide.
Now you know the retatrutide mechanism of action in detail and how this drug promotes outstanding weight loss. While this triagonist drug shows promising results, the Food and Drugs Administration (FDA) and the American Diabetes Association have still not granted their approval. Retatrutide still needs to undergo a few more studies and trials before becoming an official weight management medication. In the meantime, there are other drugs of this kind you can take advantage of to boost your weight loss journey. Schedule a call with our team to learn more about your medical weight loss options.
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