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. 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. The molecular formula is C 187 H 291 N 45 O 59 and the molecular weight is 4113.58 g/mol. Structural formula: Semaglutide is a white to almost white hygroscopic powder. RYBELSUS tablets contain 3 mg, 7 mg or 14 mg of semaglutide and the following inactive ingredients: magnesium stearate, microcrystalline cellulose, povidone and salcaprozate sodium (SNAC). OZEMPIC tablets contain 1.5 mg, 4 mg or 9 mg of semaglutide and the following inactive ingredients: magnesium stearate and SNAC. structural_formula

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.

RYBELSUS (semaglutide) tablets are available as: • 3 mg: white to light yellow, oval shaped debossed with “3” on one side and “novo” on the other side. • 7 mg: white to light yellow, oval shaped debossed with “7” on one side and “novo” on the other side. • 14 mg: white to light yellow, oval shaped debossed with “14” on one side and “novo” on the other side. OZEMPIC (semaglutide) tablets are available as: • 1.5 mg: white to light yellow, round shaped debossed with “1.5” on one side and “novo” on the other side. • 4 mg: white to light yellow, round shaped debossed with “4” on one side and “novo” on the other side. • 9 mg: white to light yellow, round shaped debossed with “9” on one side and “novo” on the other side. • RYBELSUS tablets: 3 mg, 7 mg and 14 mg • OZEMPIC tablets: 1.5 mg, 4 mg and 9 mg

• 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 • Day 1 to 30: Recommended starting dosage is 3 mg orally once daily for 30 days (this dosage is not effective for glycemic control) • Days 31 to 60: Increase the dosage to 7 mg orally once daily. • On Day 61 or thereafter, if: o No additional glycemic control is needed, maintain the dosage at 7 mg orally once daily. o Additional glycemic control is needed, increase the dosage to 14 mg orally once daily. OZEMPIC Tablets • Day 1 to 30: Recommended starting dosage is 1.5 mg orally once daily for 30 days (this dosage is not effective for glycemic control). • Days 31 to 60: Increase the dosage to 4 mg orally once daily. • On Day 61 or thereafter, if: o No additional glycemic control is needed, maintain the dosage at 4 mg orally once daily. o Additional glycemic control is needed, increase the dosage to 9 mg orally once daily

Important Administration Instructions • RYBELSUS and OZEMPIC tablets are not substitutable on a mg-to-mg basis. • Take one RYBELSUS or OZEMPIC tablet orally once daily on an empty stomach in the morning with water (up to 4 ounces of water). Do not take RYBELSUS or OZEMPIC tablets with other liquids besides water . • Do not take more than one tablet per day. • 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 . • If a dose is missed, skip the missed dose and take the next dose the following day

Recommended Starting, Escalation and Maintenance Dosage of RYBELSUS and OZEMPIC Tablets RYBELSUS: Recommended Dosage Follow the RYBELSUS starting, escalation, and maintenance dosage described below to reduce the risk of gastrointestinal (GI) adverse reactions : • Starting Dosage (Initiation Phase) (Days 1 to 30) : The recommended starting dosage is 3 mg orally once daily (this dosage is not effective for glycemic control). • Escalation and Maintenance Dosage (Days 31 and beyond) : o Days 31 to 60: Increase the dosage to 7 mg orally once daily. o On Day 61 or thereafter, if: ▪ No additional glycemic control is needed, maintain the dosage at 7 mg orally once daily. ▪ Additional glycemic control is needed, increase the dosage to 14 mg orally once daily. OZEMPIC Tablets: Recommended Dosage Follow the OZEMPIC tablets starting, escalation, and maintenance dosage described below to reduce the risk of GI adverse reactions : • Starting Dosage (Initiation Phase) (Days 1 through 30) : The recommended starting dosage is 1.5 mg orally once daily (this dosage is not effective for glycemic control). • Escalation and Maintenance Dosage (Days 31 and beyond) : o Days 31 to 60: Increase the dosage to 4 mg orally once daily. o On Day 61 or thereafter, if: ▪ No additional glycemic control is needed, maintain the dosage at 4 mg orally once daily. ▪ Additional glycemic control is needed, increase the dosage to 9 mg orally once daily

Switching Between RYBELSUS and OZEMPIC Tablets • Do not switch between RYBELSUS and OZEMPIC tablets during the initiation phase (Days 1 to 30) . • After 30 days of RYBELSUS or OZEMPIC tablet treatment (after the initiation phase) , patients may switch between RYBELSUS and OZEMPIC tablet products . • When switching between RYBELSUS and OZEMPIC tablets, initiate the other semaglutide tablet product the day after discontinuing the previous semaglutide tablet product. Table 1. Switching Between Escalation or Maintenance Dosage of RYBELSUS and OZEMPIC Tablets RYBELSUS OZEMPIC Tablets 7 mg orally once daily 4 mg orally once daily 14 mg orally once daily 9 mg orally once daily 2.4 Switching from OZEMPIC Injection to RYBELSUS or OZEMPIC Tablets Switching from OZEMPIC Injection to RYBELSUS Tablets • Patients taking the 0.5 mg dose of OZEMPIC injection may switch to RYBELSUS tablets. • One week after discontinuing 0.5 mg of subcutaneous OZEMPIC injection, start 7 mg or 14 mg of RYBELSUS orally once daily. Switching from OZEMPIC Injection to OZEMPIC Tablets • Patients taking the 0.5 mg dose of OZEMPIC injection may switch to OZEMPIC tablets. • One week after discontinuing 0.5 mg of subcutaneous OZEMPIC injection, start 4 mg or 9 mg of OZEMPIC tablets orally once daily.

• 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. • Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin : May increase the risk of hypoglycemia, including severe hypoglycemia. Reducing the dosage of insulin secretagogue or insulin may be necessary. • Acute Kidney Injury Due to Volume Depletion : Monitor renal function in patients reporting adverse reactions that could lead to volume depletion. • Severe Gastrointestinal Adverse Reactions : Use of RYBELSUS or OZEMPIC tablets has been associated with gastrointestinal adverse reactions, sometimes severe. RYBELSUS and OZEMPIC tablets are not recommended in patients with severe gastroparesis. • Hypersensitivity Reactions : Serious hypersensitivity reactions (e.g., anaphylaxis and angioedema) have been reported. Discontinue RYBELSUS or OZEMPIC tablets if hypersensitivity reactions occur and monitor until signs and symptoms resolve. • Acute Gallbladder Disease : If cholelithiasis or cholecystitis are suspected, gallbladder studies are indicated. • Pulmonary Aspiration During General Anesthesia or Deep Sedation : Has been reported in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures. Instruct patients to inform healthcare providers of any planned surgeries or procedures. 5.1 Risk of Thyroid C-Cell Tumors In mice and rats, semaglutide caused a dose-dependent and treatment-duration-dependent increase in the incidence of thyroid C-cell tumors (adenomas and carcinomas) after lifetime exposure at clinically relevant plasma 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. Cases of MTC in patients treated with liraglutide, another GLP-1 receptor agonist, have been reported in the postmarketing period; the data in these reports are insufficient to establish or exclude a causal relationship between MTC and GLP-1 receptor agonist use in humans. RYBELSUS and OZEMPIC tablets are contraindicated in patients with a personal or family history of MTC or in patients with MEN 2. Counsel patients regarding the potential risk for MTC with the use of RYBELSUS or OZEMPIC tablets and inform them of symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with RYBELSUS or OZEMPIC tablets. Such monitoring may increase the risk of unnecessary procedures, due to the low-test specificity for serum calcitonin and a high background incidence of thyroid disease. Significantly elevated serum calcitonin value may indicate MTC and patients with MTC usually have calcitonin values >50 ng/L. If serum calcitonin is measured and found to be elevated, the patient should be further evaluated. Patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated

Acute Pancreatitis Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, including semaglutide tablets . After initiation of RYBELSUS or OZEMPIC tablets, observe patients carefully for signs and symptoms of acute pancreatitis, which may include persistent or severe abdominal pain (sometimes radiating to the back), and which may or may not be accompanied by nausea or vomiting. If pancreatitis is suspected, discontinue RYBELSUS or OZEMPIC tablets and initiate appropriate management

Diabetic Retinopathy Complications In a pooled analysis of glycemic control trials, patients reported diabetic retinopathy related adverse reactions during the trial (4.2% with semaglutide tablets and 3.8% with comparator) . In a 2-year CV outcomes trial with semaglutide injection involving patients with type 2 diabetes mellitus and high CV risk, diabetic retinopathy complications (which was a 4-component adjudicated endpoint) occurred in patients treated with semaglutide injection (3%) compared to placebo (1.8%). The absolute risk increase for diabetic retinopathy complications was larger among patients with a history of diabetic retinopathy at baseline (semaglutide injection 8.2%, placebo 5.2%) than among patients without a known history of diabetic retinopathy (semaglutide injection 0.7%, placebo 0.4%). Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy. The effect of long-term glycemic control with RYBELSUS and OZEMPIC tablets on diabetic retinopathy complications has not been studied. Patients with a history of diabetic retinopathy should be monitored for progression of diabetic retinopathy

Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin Patients receiving RYBELSUS or OZEMPIC tablets in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia . The risk of hypoglycemia may be lowered by a reduction in the dosage of sulfonylurea (or other concomitantly administered insulin secretagogue) or insulin. Inform patients using these concomitant medications of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia

Acute Kidney Injury Due to Volume Depletion There have been postmarketing reports of acute kidney injury in some cases requiring hemodialysis, in patients treated with semaglutide. The majority of the reported events occurred in patients who experienced gastrointestinal reactions leading to dehydration such as nausea, vomiting, or diarrhea . Monitor renal function in patients reporting adverse reactions to RYBELSUS or OZEMPIC tablets that could lead to volume depletion, especially during dosage initiation and escalation of RYBELSUS or OZEMPIC tablets

Severe Gastrointestinal Adverse Reactions Use of semaglutide tablets has been associated with gastrointestinal adverse reactions, sometimes severe . In clinical trials, severe gastrointestinal adverse reactions were reported more frequently among patients who received semaglutide tablets (7 mg 0.6%, 14 mg 2%) than placebo (0.3%). Severe gastrointestinal adverse reactions have also been reported postmarketing with GLP-1 receptor agonists. RYBELSUS and OZEMPIC tablets are not recommended in patients with severe gastroparesis

Hypersensitivity Reactions Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) have been reported in patients treated with semaglutide tablets. If hypersensitivity reactions occur, discontinue use of RYBELSUS or OZEMPIC tablets; treat promptly per standard of care and monitor until signs and symptoms resolve. RYBELSUS and OZEMPIC tablets are contraindicated in patients with a prior serious hypersensitivity reaction to semaglutide or to any of the excipients in RYBELSUS or OZEMPIC tablets . Anaphylaxis and angioedema have been reported with GLP-1 receptor agonists. Use caution in a patient with a history of angioedema or anaphylaxis with another GLP-1 receptor agonist because it is unknown whether such patients will be predisposed to anaphylaxis with RYBELSUS or OZEMPIC tablets

Acute Gallbladder Disease Acute events of gallbladder disease such as cholelithiasis or cholecystitis have been reported in GLP-1 receptor agonist trials and postmarketing. In placebo-controlled trials to improve glycemic control, cholelithiasis was reported in 1% of patients treated with semaglutide tablets (7 mg once daily). In a 4-year CV outcomes trial (Trial 7), cholelithiasis was reported in 1.1% of patients treated with semaglutide tablets (14 mg once daily) and in 0.9% of placebo-treated patients. In Trial 7, cholecystitis was reported in 1.1% of patients treated with semaglutide tablets (14 mg once daily) and in 0.7% of placebo-treated patients . If cholelithiasis or cholecystitis is suspected, gallbladder studies and appropriate clinical follow-up are indicated

Pulmonary Aspiration During General Anesthesia or Deep Sedation RYBELSUS and OZEMPIC tablets delay gastric emptying . There have been rare postmarketing reports of pulmonary aspiration in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation who had residual gastric contents despite reported adherence to preoperative fasting recommendations. Available data are insufficient to inform recommendations to mitigate the risk of pulmonary aspiration during general anesthesia or deep sedation in patients taking RYBELSUS or OZEMPIC tablets, including whether modifying preoperative fasting recommendations or temporarily discontinuing RYBELSUS or OZEMPIC tablets could reduce the incidence of retained gastric contents. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking RYBELSUS or OZEMPIC tablets.

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

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., sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia. When initiating RYBELSUS or OZEMPIC tablets, consider reducing the dosage of concomitantly administered insulin secretagogue (such as sulfonylureas) or insulin to reduce the risk of hypoglycemia

Other Oral Drugs Semaglutide cause a delay of gastric emptying and thereby has the potential to impact the absorption of other oral drugs. Levothyroxine exposure was increased 33% (90% CI: 1.25 to 1.42) when administered with semaglutide tablets in a drug interaction study . When using RYBELSUS or OZEMPIC tablets concomitantly with other oral drugs that have a narrow therapeutic index or that require clinical monitoring, consider increased clinical or laboratory monitoring .