OZEMPIC

Indications and Usage ( 1 ) ................................................10/2025 Dosage and Administration ( 2 )...........................................12/2025 Warnings and Precautions Acute Pancreatitis ( 5.2 )...............................................10/2025 Acute Kidney Injury Due to Volume Depletion ( 5.5 ) ...........10/2025 Severe Gastrointestinal Adverse Reactions ( 5.6 ) .................10/2025 Acute Gallbladder Disease ( 5.8 ).....................................10/2025

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. ( 1 ) • 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. ( 1 )

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. ( 2.1 ) • See the Full Prescribing Information for instructions on switching between RYBELSUS and OZEMPIC tablets ( 2.3 ) and from OZEMPIC injections to RYBELSUS or OZEMPIC tablets. ( 2.4 ) Recommended Starting, Escalation and Maintenance Dosage of RYBELSUS and OZEMPIC Tablets ( 2.2 ) RYBELSUS ( 2.2 ) • 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: ( 2.2 ) 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 ( 2.2 ) • 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: ( 2.2 ) 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. 2.1 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 [see Clinical Pharmacology ( 12.3 )] . • 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 [see Clinical Pharmacology ( 12.3 )] . • If a dose is missed, skip the missed dose and take the next dose the following day. 2.2 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 [see Warnings and Precautions ( 5.6 ), Adverse Reactions ( 6.1 )] : • 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 [see Warnings and Precautions ( 5.6 ), Adverse Reactions ( 6.1 )] : • 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. 2.3 Switc …

3 DOSAGE FORMS AND STRENGTHS 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 ( 3 ) • OZEMPIC tablets: 1.5 mg, 4 mg and 9 mg ( 3 )

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 )] . • Personal or family history of MTC or in patients with MEN 2 syndrome type 2 ( 4 ) • Prior serious hypersensitivity reaction to semaglutide or any of the excipients in OZEMPIC ( 4 )

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 ( 5.5 )] • Severe Gastrointestinal Adverse Reactions [see Warnings and Precautions ( 5.6 )] • Hypersensitivity Reactions [see Warnings and Precautions ( 5.7 )] • Acute Gallbladder Disease [see Warnings and Precautions ( 5.8 )] • Pulmonary Aspiration During General Anesthesia or Deep Sedation [see Warnings and Precautions ( 5.9 )] Most common adverse reactions (incidence ≥5%) are nausea, abdominal pain, diarrhea, decreased appetite, vomiting and constipation. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novo Nordisk Inc., at 1-833-457-7455 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of OZEMPIC tablets (1.5 mg, 4 mg and 9 mg strengths) [see Dosage and Administration ( 2.2 )] and RYBELSUS (3 mg, 7, mg and 14 mg strengths) [see Dosage and Administration ( 2.2 )] has been established as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus based on adequate and well-controlled studies of RYBELSUS in adult patients with type 2 diabetes mellitus [see Clinical Pharmacology ( 12.3 ), Clinical Studies ( 14 )] . Below is a display of the safety results of the adequate and well-controlled studies of RYBELSUS (referred to below as semaglutide tablets) in adult patients with type 2 diabetes mellitus. Pool of Placebo-Controlled Trials The data in Table 2 are derived from 2 placebo-controlled trials in adult patients with type 2 diabetes mellitus [see Clinical Studies ( 14 )] . These data reflect exposure of 1,071 patients to semaglutide tablets (3 mg, 7, mg or 14 mg orally once daily) with a mean duration of exposure of 41.8 weeks. The mean age of patients was 58 years, 3.9% were 75 years or older and 52% were male. In these trials, 63% were White, 6% were Black or African American and 27% were Asian; 19% identified as Hispanic or Latino ethnicity. At baseline, patients had type 2 mellitus diabetes for an average of 9.4 years and had a mean HbA 1c of 8.1%. At baseline, 20.1% of the population reported retinopathy. Baseline estimated renal function was normal (eGFR ≥90 mL/min/1.73m 2 ) in 66.2%, mildly impaired (eGFR 60 to 90 mL/min/1.73m 2 ) in 32.4% and moderately impaired (eGFR 30 to 60 mL/min/1.73m 2 ) in 1.4% of patients. Pool of Placebo- and Active-Controlled Trials The occurrence of adverse reactions was also evaluated in a larger pool of adult patients with type 2 diabetes mellitus participating in 9 placebo- and active-controlled trials [see Clinical Studies ( 14 )] . In this pool, 4,116 patients with type 2 diabetes mellitus were treated with semaglutide tablets for a mean duration of 59.8 weeks. The mean age of patients was 58 years, 5% were 75 years or older and 55% were male. In these trials, 65% were White, 6% were Black or African American and 24% were Asian; 15% identified as Hispanic or Latino ethnicity. At baseline, patients had type 2 diabetes mellitus for an average of 8.8 years and had a mean HbA 1c of 8.2%. At baseline, 16.6% of the population reported retinopathy. Baseline estimated renal function was normal (eGFR ≥90 mL/min/1.73m 2 ) in 65.9%, mildly impaired (eGFR 60 to 90 mL/min/1.73m 2 ) in 28.5% and moderately impaired (eGFR 30 to 60 mL/min/1.73 …

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., 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 [see Warnings and Precautions ( 5.4 ), Adverse Reactions ( 6.1 )] . 7.2 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 [see Clinical Pharmacology ( 12.3 )] . 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 [see Dosage and Administration ( 2 )] .

8 USE IN SPECIFIC POPULATIONS • Pregnancy : See Pregnancy subsection. ( 8.1 ) • Lactation : Breastfeeding not recommended. ( 8.2 ) • Females and Males of Reproductive Potential : Discontinue RYBELSUS or OZEMPIC tablets in women at least 2 months before a planned pregnancy due to the long washout period for semaglutide. ( 8.3 ) 8.1 Pregnancy Risk Summary Available data with semaglutide use in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. There are clinical considerations regarding the risks of poorly controlled diabetes in pregnancy (see Clinical Considerations ). Based on animal reproduction studies, there may be potential risks to the fetus from exposure to semaglutide during pregnancy. RYBELSUS or OZEMPIC tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. In pregnant rats administered semaglutide during organogenesis, embryofetal mortality, structural abnormalities and alterations to growth occurred at maternal exposures below the maximum recommended human dose (MRHD) based on AUC. In rabbits and cynomolgus monkeys administered semaglutide during organogenesis, early pregnancy losses and structural abnormalities were observed at exposure below the MRHD (rabbit) and ≥10-fold the MRHD (monkey). These findings coincided with a marked maternal body weight loss in both animal species (see Data ). The estimated background risk of major birth defects is 6% to 10% in women with pre-gestational diabetes with an HbA 1c >7 and has been reported to be as high as 20% to 25% in women with an HbA 1c >10. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease Associated Maternal and Fetal Risk : Poorly controlled diabetes during pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth and macrosomia related morbidity. Data Animal Data : In a combined fertility and embryofetal development study in rats, subcutaneous doses of 0.01, 0.03 and 0.09 mg/kg/day (0.2-, 0.7- and 2.1-fold the MRHD) were administered to males for 4 weeks prior to and throughout mating and to females for 2 weeks prior to mating, and throughout organogenesis to Gestation Day 17. In parental animals, pharmacologically mediated reductions in body weight gain and food consumption were observed at all dose levels. In the offspring, reduced growth and fetuses with visceral (heart blood vessels) and skeletal (cranial bones, vertebra, ribs) abnormalities were observed at the human exposure. In an embryofetal development study in pregnant rabbits, subcutaneous doses of 0.0010, 0.0025 or 0.0075 mg/kg/day (0.06-, 0.6- and 4.4-fold the MRHD) were administered throughout organogenesis from Gestation Day 6 to 19. Pharmacologically mediated reductions in maternal body weight gain and food consumption were observed at all dose levels. Early pregnancy losses and increased incidences of minor visceral (kidney, liver) and skeletal (sternebra) fetal abnormalities were observed at ≥0.0025 mg/kg/day, at clinically relevant exposures. In an embryofetal development study in pregnant cynomolgus monkeys, subcutaneous doses of 0.015, 0.075 and 0.15 mg/kg twice weekly (1.9-, 9.9- and 29-fold the MRHD) were administered throughout organogenesis, from Gestation Day 16 to 50. Pharmacologically mediated, marked initial maternal body weight loss and reductions in body weight gain and food consumption coincided with the occurrence of sporadic abnormalities (vertebra, sternebra, ribs) at ≥0.075 mg/kg twice weekly (≥9X human exposure). In a pre- and postnatal development study in pregnant cynomolgus monkeys, sub …

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. 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.

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. 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

10 OVERDOSAGE In the event of overdose, appropriate supportive treatment should be initiated according to the patient’s clinical signs and symptoms. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations. A prolonged period of observation and treatment for these symptoms may be necessary, taking into account the long half-life of semaglutide of approximately 1 week.

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied RYBELSUS strengths are available as follows: Tablet Strength Description Package Configuration NDC Number 3 mg White to light yellow, oval shaped debossed with “3” on one side and “novo” on the other side Bottle of 30 tablets 0169-4303-30 7 mg White to light yellow, oval shaped debossed with “7” on one side and “novo” on the other side Bottle of 30 tablets 0169-4307-30 14 mg White to light yellow, oval shaped debossed with “14” on one side and “novo” on the other side Bottle of 30 tablets 0169-4314-30 OZEMPIC tablet strengths are available as follows: Tablet Strength Description Package Configuration NDC Number 1.5 mg White to light yellow, round shaped debossed with “1.5” on one side and “novo” on the other side Bottle of 30 tablets 0169-1715-30 4 mg White to light yellow, round shaped debossed with “4” on one side and “novo” on the other side Bottle of 30 tablets 0169-1704-30 9 mg White to light yellow, round shaped debossed with “9” on one side and “novo” on the other side Bottle of 30 tablets 0169-1709-30 Storage and Handling 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) [see USP Controlled Room Temperature]. 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.