Semaglutide

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. • 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 who are at high risk for these events.

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.

• 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. • Swallow tablets whole. Do not split, crush, chew or dissolve in any solution. • After taking RYBELSUS or OZEMPIC tablets, wait at least 30 minutes before eating food, drinking beverages or taking other oral medications. • See the Full Prescribing Information for instructions on switching between RYBELSUS and OZEMPIC tablets and from OZEMPIC injections to RYBELSUS or OZEMPIC tablets. Recommended Starting, Escalation and Maintenance Dosage of RYBELSUS and OZEMPIC Tablets. RYBELSUS.

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). • 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. • Personal or family history of MTC or in patients with MEN 2 syndrome type 2. • Prior serious hypersensitivity reaction to semaglutide or any of the excipients in OZEMPIC

Boxed 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. • Acute Pancreatitis: Has been observed in patients treated with GLP-1 receptor agonists, including RYBELSUS or OZEMPIC tablets. Discontinue if pancreatitis is suspected. • Diabetic Retinopathy Complications: Has been reported in a cardiovascular outcomes trial with semaglutide injection. Patients with a history of diabetic retinopathy should be monitored.

The following serious adverse reactions are described below or elsewhere in the prescribing information: • Risk of Thyroid C-cell Tumors • Acute Pancreatitis • Diabetic Retinopathy Complications • Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin • Acute Kidney Injury Due to Volume Depletion • Severe Gastrointestinal Adverse Reactions • Hypersensitivity Reactions • Acute Gallbladder Disease • Pulmonary Aspiration During General Anesthesia or Deep Sedation Most common adverse reactions (incidence ≥5%) are nausea, abdominal pain, diarrhea, decreased appetite, vomiting and constipation.

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.

Store RYBELSUS and OZEMPIC tablets at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F). Store and dispense in the original bottle. Store tablets in the original bottle until use to protect tablets from moisture. Store product in a dry place away from moisture.