Oral Semaglutide

Brand Names: Ozempic, Rybelsus

Drug Class: GLP-1 Receptor Agonist

Overview

11 DESCRIPTION RYBELSUS and OZEMPIC tablets, for oral use, contain semaglutide, a GLP-1 receptor agonist. The peptide 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.

Mechanism of Action

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 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.

Indications

  • 1 INDICATIONS AND USAGE RYBELSUS and OZEMPIC tablets are 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 (CV) events (CV death, non-fatal myocardial infarction or non-fatal stroke) in adults with type 2 diabetes mellitus who are at high risk for these events. RYBELSUS and OZEMPIC tablets are glucagon-like peptide-1 (GLP-1) receptor agonists indicated: • as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Common Doses

  • 3 mg
  • 7 mg
  • 14 mg
  • 1.5 mg

Dosage

2 DOSAGE AND ADMINISTRATION • RYBELSUS and OZEMPIC tablets are not substitutable on a mg-to-mg basis. • Take RYBELSUS or OZEMPIC tablets orally once daily on an empty stomach in the morning with water (up to 4 ounces of water); do not take with other liquids besides water. ( 2.1 ) • Swallow tablets whole. Do not split, crush, chew or dissolve in any solution. ( 2.1 ) • After taking RYBELSUS or OZEMPIC tablets, wait at least 30 minutes before eating food, drinking beverages or taking other oral medications. ( 2.

Black Box Warning

WARNING: RISK OF THYROID C-CELL TUMORS • In rodents, semaglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether RYBELSUS and OZEMPIC tablets cause thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined [see Warnings and Precautions ( 5.1 ), Nonclinical Toxicology ( 13.1 )] .

Contraindications

  • 4 CONTRAINDICATIONS RYBELSUS and OZEMPIC tablets are contraindicated in patients with: • A personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) [see Warnings and Precautions ( 5.1 )] . • A prior serious hypersensitivity reaction to semaglutide or to any of the excipients in RYBELSUS or OZEMPIC tablets. Serious hypersensitivity reactions including anaphylaxis and angioedema have been reported with semaglutide tablets [see Warnings and Precautions ( 5.7 )] .

Side Effects

  • 6 ADVERSE REACTIONS The following serious adverse reactions are described below or elsewhere in the prescribing information: • Risk of Thyroid C-cell Tumors [see Warnings and Precautions ( 5.1 )] • Acute Pancreatitis [see Warnings and Precautions ( 5.2 )] • Diabetic Retinopathy Complications [see Warnings and Precautions ( 5.3 )] • Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin [see Warnings and Precautions ( 5.4 )] • Acute Kidney Injury Due to Volume Depletion [see Warnings and Precautions ( 5.

Interactions

  • 7 DRUG INTERACTIONS Other Oral Drugs : RYBELSUS and OZEMPIC tablets delay gastric emptying. Consider increased clinical or laboratory monitoring when co-administered with other oral medications that have a narrow therapeutic index or that require clinical monitoring. ( 7.2 ) 7.1 Concomitant Use with an Insulin Secretagogue (e.g., Sulfonylurea) or with Insulin Semaglutide stimulates insulin release in the presence of elevated blood glucose concentrations. Patients receiving RYBELSUS or OZEMPIC tablets in combination with an insulin secretagogue (e.g.