Semaglutide Mechanism of action: Ozempic, Rybelsus, and Wegovy

Semaglutide Mechanism of action as a weight loss and anti-diabetic drug is discussed here. It is available in three different formulations as Wegovy, Ozempic, and Rybelsus.

Wegovy is the injectable formulation of Semaglutide. It is administered as a 2.4 mg once-weekly injection.

Ozempic is another once-weekly formulation of Semaglutide, however, it is administered in a dose of 0.5 mg and 1 mg once weekly compared to 2.4 mg Semaglutide.

Another formulation of Semaglutide is the oral tablet, Rybelsus, administered in a dose of 3 mg, 7 mg, and 14 mg once daily.

Semaglutide Mechanism of Action:

Semaglutide is a GLP-1 analog. It is 94% identical to the endogenous GLP-1 present in the human body.

It has a very long half-life and the drug stays in the blood for about five weeks when administered subcutaneously in contrast to the endogenous GLP-1 which has a very short half-life.

Among the three formulations of Semaglutide, Wegovy is FDA approved for weight loss in overweight and obese individuals with or without diabetes, and Ozempic and Rybelsus are only approved for the management of Diabetes.

GLP-1 (Glucagon-like peptide 1) is a peptide hormone that is released by the gut in response to a meal. GLP-1 and GIP (Glucose-dependent insulinotropic peptide, previously called gastric inhibitory peptide) are also called incretins.

The first time incretins were discovered was when scientists noticed that the administration of oral glucose resulted in a greater release of insulin compared to the intravenous administration of glucose. The term “incretins” (INtestinal seCRETion of INsulin) was suggested.

The first Incretin, Exenatide, was produced from the saliva of the GILA monster. Later, other GLP-1 analogs were discovered including Dulaglutide, Liraglutide, albiglutide, and Semaglutide.

Semaglutide Mechanism of Action as an anti-Diabetic Drug:

All three formulations of Semaglutide (Rybelsus as oral tablets, Ozempic, and Wegovy as subcutaneous insulin) are indicated for the treatment of Diabetes Mellitus Type 2. However, Wegovy is the only formulation approved for obesity even without diabetes.

Semaglutide activates the incretin receptors, resulting in the release of insulin in a glucose-dependent manner. It also suppresses the release of glucagon, thereby, inhibiting hepatic glucose output via inhibiting gluconeogenesis and glycogenolysis.

Semaglutide is thought to preserve the beta-cells of the pancreas, unlike most other anti-diabetic drugs. It inhibits the apoptosis of Beta-cells slowing Beta-cell loss.

It also causes the suppression of appetite and inhibits gastric emptying, hence, reducing postprandial hyperglycemia.

Indirectly, it suppresses the appetite center of the brain via direct stimulation of the satiety centers in the hypothalamus and also as a result of stomach stretch.

Thus, it reduces food cravings, especially for fatty meals and diets rich in carbohydrates. Semaglutide causes the slow release of food into the intestine and reduces the glucose spike which is the primary stimulus for insulin and weight gain.

Recently, it has been observed that Semaglutide and Tirzepatide inhibit cravings for alcohol and people do not have the desire to drink.

Semaglutide Mechanism of Action for Weight Loss:

Semaglutide mode of action as a weight-losing drug is thought to be its direct and indirect effects on the appetite. When used as an antidiabetic drug, it causes the release of insulin only when the blood glucose is elevated.

Thus, it does not cause significant hypoglycemia which is the main reason for increased appetite in diabetic patients.

It also causes the inhibition of gastric motility. Thus, individuals feel full all the time. Inhibition of gastric motility results in postprandial fullness.

A stretch of the stomach wall stimulates the afferent nerve endings. These nerve endings suppress the appetite by stimulating the appetite center in the hypothalamus.

The suppression of satiety via the stimulation of the appetite center in the hypothalamus is common with all GLP-1 analogs.

However, compared to other GLP-1 analogs, Semalgutide causes more weight loss. This disproportionate weight loss is thought to be a direct appetite suppression of the satiety centers by the Semaglutide [Ref].

Semaglutide suppresses hunger, and food cravings especially for fatty diets, alcohol, and foods with high glycemic indices, and better controls eating.

It also may induce vomiting and inhibits the absorption of nutrients resulting in weight loss.