Retatrutide

What Is Retatrutide?

Retatrutide is, what’s called, a GGG tri-agonist. What this means is that 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.

Retatrutide Mechanism Of Action and Weight Loss

As we already said, retatrutide peptide is a GGG tri-agonist, and its wide spectrum of activity allows it to act on:

• Gastric inhibitor receptors - this receptor plays an important role in the bodily mechanisms that affect hunger and send “fullness” signals to the brain.
• Glucagon-like receptors - these receptors slow down gastric emptying which, in turn, singlas the brain to reduce food intake. 
• Glucagon receptor - when a peptide binds to these receptors, the body is stimulated to break down stored forms of energy such as fat.

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. 

Retatrutide and Diabetes

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 carries oxygen around. And when it becomes chemically linked to sugar, we call in glycated hemoglobin. And high levels of glycated hemoglobin are caused by chronically high blood sugar levels and linked to diabetes.

So, retatrutude 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 to diabetes treatment.

Retatrutide and Cardiovascular and Heart Health

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.