*THESE STATEMENTS HAVE NOT BEEN EVALUATED BY THE FOOD AND DRUG ADMINISTRATION. THIS PRODUCT IS NOT INTENDED TO DIAGNOSE, TREAT, CURE OR PREVENT ANY DISEASE.
Retatrutide, also known as LY3437943, is a glucagon-like peptide 1 agonist; what separates this peptide from the others is it also targets gastric inhibitory polypeptide receptor (GIPR) and glucagon receptors (GCGR), making it a triagonist.
In the lab settings, Retatrutide mimics the natural glucagon and glucose production within the hepatocytes, while inducing lipolysis in the adipocytes.
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Retatrutide is, what’s called, a GGG tri-agonist, which means it works at GLP-1, GIP and glucagon receptors. The significance of its tri-agonist action is huge since researchers believe Retatrutide might just be the most effective weight loss peptide ever developed and tested in an in-vitro environment.
Studies in obese mice showed that most prolific test subjects lost an astounding 24% of their total body weight! It’s believed that such significant weight loss was achieved through its dual action of both increasing energy expenditure and decreasing energy consumption.
The peptide itself was based off of GIP, which was further modified to allow it to bind to albumin in the bloodstream. And, since albumin is the most abundant blood’s protein, this modification allowed Retatrutide to spread out quickly and remain in the bloodstream much longer. This increased half-life reduced the dosage frequency to as little as once weekly.
As we already said, Retatrutide peptide is a GGG tri-agonist, and its wide spectrum of activity allows it to act on:
It’s important to note these were all findings from the in vivo studies, done on actual human test subjects. The study showed Retatrutide as being a far superior peptide (compared to others) with regards to weight loss over time. Scientists believe this is, in part, due to its ability to slow down gastric emptying, signaling the brain to reduce food intake. This allows for better hunger control, more energy from less food and a gradual weight loss reduction with incredible results.
Though these findings were extrapolated from human studies, this peptide still needs a lot of development to be used as a viable weight loss drug, for the time being, its use is only experimental.
Studies on rats, on the other hand, showed incredible weight loss results in overweight rodents. In a 10-day study, its effectiveness was measured against Semaglutide. The results showed that, when administered in the same dosages, Retatrutide leads to far superior weight loss. This is why this peptide became so interesting to researchers since it can be administered in lower dosages and help those patients who’ve developed a resistance to semaglutide.
In one of the phase 2 studies involving diabetes, we saw this peptide leading to a significant reduction in glycated hemoglobin. For those of you that don’t know, hemoglobin is a substance found in the blood which transports oxygen. And when it becomes chemically linked to sugar, we call it glycated hemoglobin. And high levels of glycated hemoglobin are caused by chronically high blood sugar levels and linked to diabetes.
So, Retatrutide did not only prove itself in the weight loss arena, but there are strong indications it can help people struggling with diabetes. Furthermore, it requires lower dosage when compared to Semaglutide, leading scientists to speculate it might be a safer alternative for this form of diabetes treatment.
The effects of Retatrutide have not yet been tested in humans, sadly, but we’ve seen some on cynomolgus macaques. These primates are used in clinical trials because of their genetic and physiological similarity to humans.
This study showed that Retatrutide caused increased heart rate while simultaneously reduced blood pressure. This was a rather interesting find which confirmed what we already knew about the effects of glucagon - which is also used in patients who’ve suffered from heart failure, to augment the heart rate and increase cardiac contractility.
Research also showed that incretins (hormones, members of the glucagon superfamily), have a beneficial effect on the heart by reducing blood pressure, improving ventricular functions and vasodilatation. Being that Retatrutide affects glucagon receptors, it's reasonable to believe it will lead to positive cardiovascular outcomes but these claims still need further testing.
Due to its high metabolic activity, liver tissue can also play a crucial role in overall metabolism and homeostasis. Research showed that the Retatrutide peptide may increase this activity by aiming GCG receptors in hepatic cells, which potentially leads to an increased metabolic rate and enhanced fat breakdown within the liver. Furthermore, by stimulating these receptors in the liver, Retatrutide may initiate metabolic processes that induce weight loss. However, more research is still needed to fully understand this connection.
Studies hypothesized that Retatrutide might interact with the central nervous system, GLP-1 and GIP receptors in particular, by which it may potentially have an effect on energy regulation and appetite. Such stimulation may further indirectly activate neurons within the hypothalamic arcuate nucleus, leading to the production of amphetamine-regulated transcript. Furthermore, research also showed that this action may suppress the secretion of hunger-promoting peptides - neuropeptide Y (NPY) and agouti-related peptide (AgRP).
In addition, researchers believe that Retatrutide might activate GIP receptors in other brain parts, potentially increasing the signal that promotes feeling of fullness.
To sum up, as science is constantly developing and there are new advancements, researchers will continue to uncover new insights and potential benefits of peptides, with Retatrutide standing out as an exceptional example.
Its distinctive tri-agonist activity on GIP, GLP-1, and glucagon receptors opens the door for new, innovative research into diabetes regulation, weight loss, and cardiovascular health. While the findings so far sound promising, further research is still necessary to fully understand its effects and ensure safety.
It’s important to know that Retatrutide is not approved for human use and is currently used for research purposes only. However, as the researchers continue to work on new discoveries, the future studies may reveal additional proven benefits of this peptide, providing new hope for medical use and application.
Resources:
World Obesity Federation. World obesity atlas 2023. March 2023 (https://data.worldobesity.org/publications/?cat=19).
Rosen CJ, Ingelfinger JR. Shifting tides offer new hope for obesity. N Engl J Med 2022;387:271-273.
Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med 2022;387:205-216.
Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med 2021;384:989-1002.
Day JW, Ottaway N, Patterson JT, et al. A new glucagon and GLP-1 co-agonist eliminates obesity in rodents. Nat Chem Biol 2009;5:749-757.
Finan B, Yang B, Ottaway N, et al. A rationally designed monomeric peptide triagonist corrects obesity and diabetes in rodents. Nat Med 2015;21:27-36.
The power of three: Retatrutide's role in modern obesity and diabetes therapy -
Toufik Abdul-Rahman Poulami Roy, Fatma Kamal Ahmed, Jann Ludwig Mueller-Gomez, Sarmistha Sarkar, Neil Garg, Victor Oluwafemi Femi-Lawal, Andrew Awuah Wireko, Hala Ibrahim Thaalibi, Muhammad Usman Hashmi, Andrew Sefenu Dzebu, Sewar Basheer Banimusa, Aayushi Sood
Retatrutide
retatrutide 3 5mg
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