OZEMPIC is indicated:
- • as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
- • to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease.
WEGOVY is indicated as an adjunct to a reduced calorie diet and increased physical activity for chronic weight management in:
- • adults with an initial body mass index (BMI) of:
- o 30 kg/m2 or greater (obesity) or
- o 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbid condition (e.g., hypertension, type 2 diabetes mellitus, or dyslipidemia)
- • pediatric patients aged 12 years and older with an initial BMI at the 95th percentile or greater standardized for age and sex (obesity)
- RYBELSUS is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
- API Properties
- Semaglutide is a white to almost white hygroscopic powder, it has the following structure:
Semaglutide's backbone is produced by yeast fermentation. The main protraction mechanism of semaglutide is albumin binding, facilitated by modification of position 26 lysine with a hydrophilic spacer and a C18 fatty di-acid. Furthermore, semaglutide is modified in position 8 to provide stabilization against degradation by the enzyme dipeptidyl-peptidase 4 (DPP-4). A minor modification was made in position 34 to ensure the attachment of only one fatty di-acid.Semaglutide is a GLP-1 analogue with 94% sequence homology to human GLP-1. Semaglutide acts as a GLP-1 receptor agonist that selectively binds to and activates the GLP-1 receptor, the target for native GLP-1. GLP-1 is a physiological hormone that has multiple actions on glucose, mediated by the GLP-1 receptors.
The principal mechanism of protraction resulting in the long half-life of semaglutide is albumin binding, which results in decreased renal clearance and protection from metabolic degradation. Furthermore, semaglutide is stabilized against degradation by the DPP-4 enzyme.
Semaglutide reduces blood glucose through a mechanism where it stimulates insulin secretion and lowers glucagon secretion, both in a glucose-dependent manner. Thus, when blood glucose is high, insulin secretion is stimulated and glucagon secretion is inhibited. The mechanism of blood glucose lowering also involves a minor delay in gastric emptying in the early postprandial phase.
PK of RYBELSUS, The Oral Tablet
Semaglutide is co-formulated with salcaprozate sodium which facilitates the absorption of semaglutide after oral administration. The absorption of semaglutide predominantly occurs in the stomach. Following oral administration, maximum concentration of semaglutide is reached 1-hour post-dose. Steady-state exposure is achieved following 4-5 weeks administration. The estimated absolute bioavailability of semaglutide is about 0.4%-1%, following oral administration. However, semaglutide is extensively bound to plasma albumin (>99%). Thus, its elimination half-life is long, about 1 week, and semaglutide is present in the circulation for about 5 weeks after the last dose. Approximately 3% of the absorbed dose is excreted in the urine as intact semaglutide.
Each tablet of RYBELSUS contains 3 mg, 7 mg or 14 mg of semaglutide and the following inactive ingredients: magnesium stearate, microcrystalline cellulose, povidone and salcaprozate sodium (SNAC). Salcaprozate sodium, also known as SNAC or sodium N-[8-(2-hydroxybenzoyl)amino] caprylate, is a synthetic N-acetylated amino-acid derivative of salicylic acid. It is a weak acid that displays amphiphilicity and surface activity. SNAC is one of the most widely used small molecules as a penetration enhancer for peptide delivery. (Orange Book Patent: 9278123, Expires on 12/16/2031)
Subcutaneous Administration
Absolute bioavailability of semaglutide is 89%. Maximum concentration of semaglutide is reached 1 to 3 days post dose. Similar exposure was achieved with subcutaneous administration of semaglutide in the abdomen, thigh, or upper arm.
The steady state exposure of WEGOVY increased proportionally with doses up to 2.4 mg once weekly.
With an elimination half-life of approximately 1 week, semaglutide will be present in the circulation for about 5 to 7 weeks after the last dose of 2.4 mg. The primary excretion routes of semaglutide-related material are via the urine and feces. Approximately 3% of the dose is excreted in the urine as intact semaglutide.
Each 1 mL of WEGOVY contains the following inactive ingredients: disodium phosphate dihydrate, 1.42 mg; sodium chloride, 8.25 mg; and water for injection. WEGOVY has a pH of approximately 7.4. Hydrochloric acid or sodium hydroxide may be added to adjust pH.
Each 1 mL of OZEMPIC solution also contains the following inactive ingredients: disodium phosphate dihydrate, 1.42 mg; propylene glycol, 14.0 mg; phenol, 5.50 mg; and water for injections. OZEMPIC has a pH of approximately 7.4. Hydrochloric acid or sodium hydroxide may be added to adjust pH.
