Scientists toil and strive to develop medicines, unknown to the masses, while celebrities instantly make

products widely known. Do you know what Semaglutide is? But you surely know that the billionaire Elon

Musk injected an appetite suppressant and showcased a rapidly slimmed-down physique – that’s

Semaglutide, whose market name is Wegovy or Ozempic. With Musk's demonstration in the forefront,

an increasing number of people are eager to follow suit, hoping to rescue their own obesity through

medication.

Obese individuals normally have abnormal hormone responses to nutrient intake, which results in

metabolic dysfunction. Consequently, their cells become less responsive to insulin’s actions, their

glucose and fatty acid refuse to break down, their “hunger hormones” keep them over-eating all the

time, their fat cells are easier to accumulate around their belly, and they are easier to develop diseases

such as diabetes and hypertension. In a nutshell, obesity is a kind of chronic disease which is not easy to

cure by mere diet or working out.

There are three important hormones that are abnormally regulated in obese individuals: glucagon-like

peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon (GCG), the three

Gs. The main actions of GLP-1 is like a “sugar reducer”. It can stimulate insulin secretion and inhibit

glucagon secretion, thereby helping to control the spikes in blood sugar after eating. GCG works like a

"sugar booster" and it does the opposite of insulin, making your blood sugar go up instead of down. GIP

functions as a “fat manager”. It affects how your body deals with fats by stopping the breakdown of fats

and encouraging the creation of new fats, sounding like a nightmare for obese, but it also stimulates

satiety and makes you have less appetite in eating.

Semaglutide, the renowned worldwide chemical thanks to Musk, can activate GLP-1 receptors, helping

the body to release more insulin when needed, stopping the release of GCG (the sugar booster), and

decreasing the production of sugar by the liver. In conclusion, Semaglutide can effectively reduce blood

glucose levels before and after meals. Semaglutide is already in phase 3 trials now and really a blessing

for the obese. Another peptide molecule in phase 3 trial is Tirzepatide, whose brand name is Mounjaro,

acts as a “dual helper” on both GLP-1 and GIP receptors. It makes the body's natural sugar-regulating

system work better and acts on certain regions of the brain to suppress food intake. NBA icon Charles

Barkley is among the celebrities who openly acknowledged their utilization of Tirzepatide, leading to a

remarkable weight loss of over 60 pounds.

In fact, Musk could wait for a while before losing weight with Semaglutide. The new rising star in

combating obesity, Retatrutide, might outperform the effects of Semaglutide! Retatrutide is a peptide

that can activate all three G receptors (GLP-1, GIP , and GCG). The working mechanism of Retatrutide

sounds a little strange: what is the point to stimulate the “sugar reducer”，the “sugar booster”, and the

“fat manager” at the same time? However, it works more efficiently when three Gs are activated than

only one or two Gs are activated. Retatrutide is much more potent at activating the “sugar reducer”

than the “sugar booster”. Other scientists have also proved on animal experiments that when the “sugar

reducer” was fully activated, adding some stimulation of the “sugar booster” will help to burn the body

fat better.

The exciting results from Jastreboff etc, was published on N ENGL J MED 389;6 nejm.org August 10,

2023, titled "Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial". In this

research, Retatrutide or placebo in different doses was injected under the participants‘skins once every

week. After 24 weeks, Retatrutide was found to substantially reduce the body weight of obese

individuals by 7.2% to 17.5%. With trial time extended to 48 weeks, the efficacy of Retatrutide worked

even better that the body weight of the attended individuals decreased 8.7% to 24.2%. The reduction

was dose related. The higher the dose, the better the weight-losing effects. The body weights of the

placebo group only reduced 1.6% and 2.1%, at 24 and 48 weeks, respectively.

The adverse events associated with Retatrutide were generally mild to moderate, primarily as

gastrointestinal symptoms such as nausea, diarrhea, vomiting, and constipation. These effects were

observed to be dose-dependent. Additionally, a minority of participants experienced elevated heart

rates at 24 weeks; however, the heart rates reverted to normal levels as the medication application

continued through the 36- and 48-week periods.

Given the marked success of the phase 2 trial involving Retatrutide, there is a prospective advancement

into the upcoming Phase 3 stage. This pivotal phase will involve a larger and more diverse population

encompassing a wider range of racial and geographic backgrounds. Notably, the phase 2 trial

predominantly enrolled individuals of white ethnicity. The Phase 3 trial aims to comprehensively assess

the optimal dosage, treatment duration, and long-term safety profile of Retatrutide.

As a potential future beneficiary of this medication, you might be a bit curious whether it's necessary for

you to use it for weight loss. Below are the selection criteria for participants in the Phase 2 clinical trial:

1. Age between 18 to 75 years.

2. Body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) of 30

to 50.

3. 27< BMI < 30 in addition to at least one weight-related condition: waist circumference > 100 cm,

prediabetes, hypertension, or dyslipidemia.

If you fail to meet the criteria, congratulations! Largely, you don’t need to worry about your chubby face

or somewhat plump figure. Just eat less and move more!