Semaglutide

Brand Names: Ozempic

Drug Class: GLP-1 Receptor Agonist

Overview

11 DESCRIPTION OZEMPIC (semaglutide) injection, for subcutaneous use, contains semaglutide, a human GLP-1 receptor agonist (or GLP-1 analog). 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 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. Limitations of Use • OZEMPIC has not been studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis [see Warnings and Precautions ( 5.2 )] .

Common Doses

  • 0.25 mg
  • 0.5 mg
  • 1 mg
  • 2 mg

Dosage

2 DOSAGE AND ADMINISTRATION • Administer once weekly at any time of day, with or without meals ( 2.1 ). • Start at 0.25 mg once weekly. After 4 weeks, increase the dosage to 0.5 mg once weekly ( 2.2 ). • If additional glycemic control is needed, increase the dosage to 1 mg once weekly after at least 4 weeks on the 0.5 mg dose ( 2.2 ). • If additional glycemic control is needed, increase the dosage to 2 mg once weekly after at least 4 weeks on the 1 mg dosage ( 2.2 ). • If a dose is missed administer within 5 days of missed dose ( 2.2 ).

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 OZEMPIC causes 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 ) and Nonclinical Toxicology ( 13.1 )] .

Contraindications

  • 4 CONTRAINDICATIONS OZEMPIC is contraindicated in patients with: • A personal or family history of MTC or in patients with MEN 2 [see Warnings and Precautions ( 5.1 )] . • A serious hypersensitivity reaction to semaglutide or to any of the excipients in OZEMPIC. Serious hypersensitivity reactions including anaphylaxis and angioedema have been reported with OZEMPIC [see Warnings and Precautions ( 5.7 )] . • Personal or family history of MTC or in patients with MEN 2 ( 4 ). • Serious hypersensitivity reaction to semaglutide or any of the excipients in OZEMPIC ( 4 ).

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 )] • 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 ( 5.5 )] • Acute Kidney Injury [see Warnings and Precautions ( 5.6 )] • Hypersensitivity [see Warnings and Precautions ( 5.

Interactions

  • 7 DRUG INTERACTIONS Oral Medications : OZEMPIC delays gastric emptying. May impact absorption of concomitantly administered oral medications. Use with caution ( 7.2 ). 7.1 Concomitant Use with an Insulin Secretagogue (e.g., Sulfonylurea) or with Insulin OZEMPIC stimulates insulin release in the presence of elevated blood glucose concentrations. Patients receiving OZEMPIC in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia.