Retatrutide- Upcoming Revolution in Obesity Treatment

Retatrutide is still in the development stages. However, it is pretty likely to be soon approved for managing obesity. When approved, it will become the first-ever drug belonging to the new class of drugs that are GLP-1, GIP, and Glucagon receptor agonists. It would be the first drug that acts on all these three receptors. Hence, it is expected to be one of the most potent weight loss drugs ever introduced by science. Drugs acting on these receptors are known to be safe, and hence, Retatrutide appears to be safe for prolonged use.

It would be somewhat right to call Retatrutide an evolution. This drug has been developed through years of research that shows the right way to treat obesity. Over the years, studies have shown how to counter obesity and what receptors to stimulate or suppress. Hundreds of previous studies have shown that boosting incretins by stimulating GLP-1 and GIP receptors is the best way to reduce body weight.

However, all previous drugs that were GLP-1 and GIP receptor stimulants or agonists were first approved for managing diabetes. This is because stimulating these receptors increases insulin production and promotes insulin sensitivity. Later, these drugs were repurposed for managing obesity, as they were equally good for weight loss. The two most potent weight loss drugs, semaglutide, and tirzepatide, are examples of these newly approved weight loss drugs that were initially approved for managing diabetes.

However, using anti-diabetes drugs has some drawbacks. They still stimulate insulin production and reduce blood glucose a bit, something that is not needed for obese patients. Hence, researchers have started thinking, why not develop a drug similar to semaglutide and tirzepatide yet created explicitly for weight loss? It appears that they have finally found the right drug, which is the form of Retatrutide.

This article will explain in detail what makes Retatrutide unique and what differentiates it from blockbuster weight loss drugs like semaglutide/Ozempic and tirzepatide. We will discuss how this drug is safer and better, and it is expected to revolutionize obesity treatment forever.

How Retatrutide Works?

Over the years, researchers have developed a better understanding of obesity,  and they have understood that it is a multi-faceted disease. Till the 20^th century, obesity was viewed merely as a behavioral disorder characterized by excessive food consumption by prosperous people. However, now researchers have understood that obesity is also about hormonal disorders, brain changes, and more. Moreover, obesity is now recognized as a disease that must be treated.(1)

The US has become the first nation to classify obesity as a disease and not merely a risk factor for other health conditions. Experts reached this conclusion through decades of research. Obesity kills and causes disability in hundreds of ways. It increases the risk of heart attack, stroke, diabetes, cancer, and most ailments, and it also causes much disability by harming joints and causing mental distress.

It is evident that obesity is no longer a problem for a few people. More than 70% of people in the US are either obese or overweight, making it the fattest nation in the world. However, the trend is similar in the EU and even in the developing countries. Thus, the only way to control non-infectious diseases is to start treating obesity. Hence, the discovery of drugs like Retatrutide cannot be understated.

Now, let’s see how Retatrutide works and what makes it unique and the most effective weight loss drug to date.

Understanding Incretins

In the late 19^th century and early 20^th century, researchers realized that the human gut secretes many hormones and is a powerful endocrinal organ. Many hormones are secreted in response to food intake. These hormones prepare the body for further food processing. Thus, incretins are released by the gut to increase insulin production. These hormones also slow down gastric emptying to promote digestion and increase satiety – signaling the brain not to consume too much food. Hence, these hormones or incretins play an important role in appetite regulation and metabolism.(2)

Over the years, researchers have realized that excessive eating and faulty lifestyle choices affect production of gut hormones like incretins. These changes/dysregulation in incretin production cause obesity, diabetes, and various other metabolic disorders. These findings prove that obesity is a complex disease, and it also explains why measures like exercise and diet frequently fail to help.(2)

Science has now understood that two peptides (large protein molecules) that are GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1), secreted by the gut are two of the most potent incretins playing a vital role in energy metabolism. Thus, these hormones have become the target of many modern treatment approaches.(2)

However, the more we learn, the more we discover. It seems that the human gut produces tens of hormones or peptides. Science is still exploring its role in health and well-being. Thus, we might see more drug therapies targeting different gut peptides in the future.(3)

GLP-1 & GIP Hormones and Incretins Mimetics

Some of the latest blockbuster anti-obesity/weight loss drugs target two of the most potent incretins, that is GLP-1 and GIP. Thus, semaglutide/Ozempic/Wegovy targets GLP-1. However, more potent drugs like Retatrutide target both GLP-1 and GIP hormones. Both these incretins have similarities, but they also have some differences.

Thus, Retatrutide is incretin mimetic, meaning it increases the production of incretins like GLP-1 and GIP. It does this by acting on specific gut receptors.

Both the GLP-1 and GIP slow down gastric emptying, and they reduce appetite. This is the primary way in which Retatrutide works, helping with weight loss. It reduces appetite in two ways: slowing down gut movement and influencing the part of the brain that regulates appetite.

Retatrutide also increases insulin and beta-cell production; thus, it is also good for those with diabetes.

GLP-1 and GIP agonists like Retatrutide also improve memory and brain health, promoting nerve growth. These hormones are generally quite good for heart health, too. Thus, using them also boosts cardiovascular health. It means that treatment with Retatrutide is bound to reduce heart attack and stroke risk.

However, there are also minute differences in GLP-1 and GIP. GIP hormone also produces an accumulation of excessive energy into fat cells – this may be counterproductive if one does not use dietary measures when taking the drug. GIP also increases glucagon a bit, thus helping prevent a significant decline in blood glucose levels. Additionally, GIP is excellent for bone health. Overall, using a drug that acts on both GLP-1 and GIP has many added health benefits.(4)

Glucagon & Health

Retatrutide is unique in one way. It is the first drug in its class that not only boosts GLP-1 and GIP production by the gut but also glucagon receptors, significantly boosting its production. Thus, it is a triple receptor agonist (GLP-1, GIP, and Glucagon). This makes this drug unique in many ways from pre-existing medication.(5)

Semaglutide is a GLP-1 agonist, and tirzepatide is GLP-1 and GIP agonist. However, Retatrutide is a step forward, and it is a tri-receptor agonist, thus acting on GLP-1, GIP, and glucagon.

As one can see, what makes retatrutide drug different from other anti-obesity drugs is its impact on glucagon receptors. This effect on glucagon receptors has both its pros and cons. Any drug-increasing glucagon is not suitable for managing diabetes. It means that, unlike semaglutide or tirzepatide, it is mainly for managing obesity. Increased glucagon is suitable for managing in many ways.

In the human body, everything is balanced. If there are excitatory molecules, then there are inhibitory molecules, and the balance of the two molecules ensures the balance in the body or homeostasis.

Hence, if there is an insulin that boosts glucose use by cells and reduces blood glucose levels, then there is a glucagon that increases blood glucose. Together, these two hormones are responsible for maintaining the balance inside the body.(6)

Glucagon is not good for people with diabetes. However, for obese patients without diabetes, it has many benefits. It increases weight loss as it promotes the burning of calories. It is also known to promote the burning of fat tissues significantly. It increases the burning of fats in the liver. Simply put, it overcomes some of the negatives of the increased insulin production caused by GLP-1 and GIP hormones. Hence, acting on all three receptors results in even more potent weight loss action. However, it does not result in any significant increase in blood glucose levels due to increased insulin production. Stimulating all three receptors together (GLP-1, GIP, and Glucagon) results in a powerful boost in metabolic rate.(6)

In short, Retatrutide builds on what was already known to science. It also tries to overcome some of the deficiencies of drugs that increase only GLP-1 or GIP. Moreover, what sets this drug apart from all previous incretin mimetics (drugs that increase incretins) is that it is specifically made for weight loss in non-diabetics. This is unlike the older drugs that were first created to manage diabetes and then repurposed. This drug is already in the final stages of its approval for managing obesity.

Of course, this does not mean that this drug is not for people with diabetes. It is also good for managing diabetes, as it increases insulin production. Any drug that boosts metabolic rate is good for managing diabetes. However, its triple action makes it unique, and there are real possibilities that the FDA will soon approve it for controlling the range of metabolic health issues.

What Does the Science Says?

Retatrutide has already gone through various clinical trials, and the results of most of those studies were as expected. The studies show that it is the most potent anti-obesity drug ever discovered by science. Not only does it result in much greater weight loss, but also in a much shorter time.

Thus, for example, semaglutide, the most popular drug, can help lose, on average, 15% of body weight in about one and a half years, whereas tirzepatide helps lose almost 20% of body weight at the same time. However, studies show that Retatrutide may help lose 17.5% of body weight in just six months and as much as 24.4% or even more body weight in merely 48 weeks or about 11 months.(5,7)

What we are seeing is the emergence of the most effective weight loss drug ever created by science. What is good about Retatrutide is that it is not just potent but works much faster. Most people may achieve their weight loss target within six months if they combine it with dietary measures and exercise. However, almost all patients can expect to have significant weight loss within less than one year.

Retatrutide is comfortable to use like all other incretin mimetics. It means that the drug is given subcutaneously or below the skin on a weekly basis. Doctors would generally start with a lower dose and increase its dosage gradually every few weeks, depending on the results and how well one tolerates the drug.

Here, one more thing is worth noticing: 24.5% is the average weight loss of participants in one of the clinical studies.(5) It means that even greater weight loss is possible if the drug is combined with extensive lifestyle interventions. This means that perhaps most people who follow lifestyle recommendations can expect to get rid of obesity in six to eleven months by using this drug weekly. This is an excellent report, as for the first time, there is real hope that obesity can be treated with the help of medications without using any surgical interventions.

There is one more important thing to know about this drug. This drug is expected to be approved immediately for managing diabetes. This means that it will help lower blood sugar levels in those living with diabetes. However, it will not lower blood sugar levels in healthy adults.(5)

But, perhaps even more important news is that this drug is expected to be approved for managing non-alcoholic fatty liver disease (NAFLD). NAFLD is the leading cause of liver cancer. NAFLD is associated with chronic inflammation, immune dysregulation, and many other health issues. Retatrutide can help reduce fat accumulation in the liver.(5)

It also means that Retatrutide is good for burning resistant fat accumulation. Hence, it will be quite good for those living with central obesity. That is, individuals with fat accumulation on the tummy. Such people often find it hard to get rid of their problem, and central obesity may persist even after the weight loss.

The studies have many other encouraging findings. Retatrutide may not only help lower body weight and blood glucose levels. It can significantly help lower bad cholesterol levels. It reduces total cholesterol, triglycerides, and LDL cholesterol levels but does not affect good cholesterol or HDL cholesterol levels. Even more incredible are the findings that it can even help lower blood pressure.(8)

So, we are seeing the emergence of a drug that not only helps with weight loss but also boosts metabolism. It would be correct to say that this drug is a treatment for metabolic disorders. Hence, it would improve the full spectrum of metabolic changes that occur secondary to obesity. Thus, it reduces body weight and accelerates the reversal of changes that occur secondary to chronic obesity in the body. The expectations from this drug are really high, and it is possible that it would help get rid of a range of health issues, including lowering the risk of osteoarthritis and obstructive sleep apnea, preventing type 2 diabetes, enhancing memory, and boosting brain function.(5)

When it comes to safety, its side effects are similar to other drugs affecting incretins, though they appear to be milder. Hence, despite being more potent than any of the existing drugs, it also seems to be safer. What more can people living with obesity ask for? Thus, it causes mild nausea, vomiting, and diarrhea or constipation when starting the drug therapy. However, these side effects are transient, and people soon get used to the medication.

The Bottom Line

The introduction of retatrutide is going to change the treatment of obesity forever. It is the most potent weight loss drug ever discovered by the science. This drug’s mechanism of action makes it unique, as it is GLP-1, GIP, and Glucagon agonist. This makes this drug not just one of the most effective weight loss drugs but also a highly safe drug with numerous health benefits.

This drug is good for managing a range of metabolic health issues. It helps with weight loss much faster than existing drugs, and most people using this drug can expect to achieve their targets in just six to twelve months. This drug has a range of other benefits, such as its effectiveness in almost 100% of cases when used regularly. It can also reverse central obesity and diabetes, help eliminate non-alcoholic fatty liver disease, reduce bad cholesterol, and lower blood pressure. So, it could be seen as a medication that can cure metabolic syndrome.

This drug will likely change obesity treatment forever. Till now, grossly overweight individuals have only one effective way of weight loss, which is surgical treatment. However, this drug is suitable for a vast range of patients, from mildly to grossly obese. It is even suitable for overweight individuals with signs of metabolic disorders.

References

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3. Rehfeld JF. The Origin and Understanding of the Incretin Concept. Front Endocrinol (Lausanne). 2018 Jul 16;9:387.
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