How Much Does Semaglutide Cost in Mexico vs the USA?

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 )

• 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 Switching Between RYBELSUS and OZEMPIC Tablets • Do not switch between RYBELSUS and OZEMPIC tablets during the initiation phase (Days 1 to 30) [see Dosage and Administration ( 2.2 )] . • After 30 days of RYBELSUS or OZEMPIC tablet treatment (after the initiation phase) [see Dosage and Administration ( 2.2 )] , patients may switch between RYBELSUS and OZEMPIC tablet products (see Table 1 ). • 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.

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 )

• Acute Pancreatitis : Has been observed in patients treated with GLP-1 receptor agonists, including RYBELSUS or OZEMPIC tablets. Discontinue if pancreatitis is suspected. ( 5.2 ) • Diabetic Retinopathy Complications : Has been reported in a cardiovascular outcomes trial with semaglutide injection. Patients with a history of diabetic retinopathy should be monitored. ( 5.3 ) • 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. ( 5.4 ) • Acute Kidney Injury Due to Volume Depletion : Monitor renal function in patients reporting adverse reactions that could lead to volume depletion. ( 5.5 ) • 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. ( 5.6 ) • 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. ( 5.7 ) • Acute Gallbladder Disease : If cholelithiasis or cholecystitis are suspected, gallbladder studies are indicated. ( 5.8 ) • 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. ( 5.9 ) 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 [see Nonclinical Toxicology ( 13.1 )] . 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. 5.2 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 [see Adverse Reactions ( 6 )] . 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. 5.3 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) [see Adverse Reactions ( 6.1 )] . 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. 5.4 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 [see Adverse Reactions ( 6.1 ), Drug Interactions ( 7 )] . 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. 5.5 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 [see Adverse Reactions ( 6 )] . 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. 5.6 Severe Gastrointestinal Adverse Reactions Use of semaglutide tablets has been associated with gastrointestinal adverse reactions, sometimes severe [see Adverse Reactions ( 6.1 )] . 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. 5.7 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 [see Adverse Reactions ( 6.2 )] . 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. 5.8 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 [see Adverse Reactions ( 6.1 )] . If cholelithiasis or cholecystitis is suspected, gallbladder studies and appropriate clinical follow-up are indicated [see Adverse Reactions ( 6.2 )] . 5.9 Pulmonary Aspiration During General Anesthesia or Deep Sedation RYBELSUS and OZEMPIC tablets delay gastric emptying [see Clinical Pharmacology ( 12.2 )] . 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. ( 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 )] .

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/1.73m 2 ) in 5.4% of the patients. Common Adverse Reactions Table 2 shows common adverse reactions, excluding hypoglycemia, associated with the use of semaglutide tablets in adult patients with type 2 diabetes mellitus in the pool of placebo-controlled trials. These adverse reactions occurred more commonly on semaglutide tablets than on placebo and occurred in at least 5% of patients treated with semaglutide tablets. Table 2. Adverse Reactions in Placebo-Controlled Trials Reported in ≥5% of Semaglutide Tablets-Treated Patients with Type 2 Diabetes Mellitus Adverse Reaction Placebo (N=362) % Semaglutide Tablets 7 mg (N=356) % Semaglutide Tablets 14 mg (N=356) % Nausea 6 11 20 Abdominal Pain 4 10 11 Diarrhea 4 9 10 Decreased appetite 1 6 9 Vomiting 3 6 8 Constipation 2 6 5 In the pool of placebo- and active-controlled trials, the types and frequency of common adverse reactions, excluding hypoglycemia, were similar to those listed in Table 2 . In a 4-year CV outcomes trial (Trial 7), 4,825 patients were randomized to semaglutide tablets for a median follow-up of 49.6 months and 4,825 patients were randomized to placebo for a median follow-up of 49.4 months [see Clinical Studies ( 14.4 )] . Safety data collection was limited to serious adverse events (including death), adverse events leading to discontinuation, and adverse events of special interest. Study drug was permanently discontinued due to an adverse event in 15.5% of semaglutide tablets-treated patients and 11.6% of placebo-treated patients. Additional information from this trial is included in subsequent sections below, when relevant. Gastrointestinal Adverse Reactions In the pool of placebo-controlled trials, gastrointestinal adverse reactions occurred more frequently among patients who received semaglutide tablets than placebo: semaglutide tablets 14 mg once daily (41%), semaglutide tablets 7 mg once daily (32%) and placebo (21%), including severe reactions (semaglutide tablets 14 mg 2.0%, semaglutide tablets 7 mg 0.6%, placebo 0.3%). The majority of reports of nausea, vomiting and/or diarrhea occurred during dose escalation. A greater percentage of patients who received semaglutide tablets 14 mg once daily (8%) and semaglutide tablets 7 mg once daily (4%) discontinued treatment due to gastrointestinal adverse reactions than patients who received placebo (1%). In addition to the reactions in Table 2 , the following gastrointestinal adverse reactions with a frequency of <5% occurred in semaglutide tablets -treated patients (frequencies listed, respectively, as 14 mg once daily, 7 mg once daily and placebo): abdominal distension (3%, 2% and 1%), dyspepsia (0.6%, 3%, 0.6%), eructation (2%, 0.6%, 0%,), flatulence (1%, 2%, 0%), gastroesophageal reflux disease (2%, 2%, 0.3%) and gastritis (2%, 2%, 0.8%). Other Adverse Reactions Pancreatitis : In the pool of placebo- and active-controlled trials with semaglutide tablets, pancreatitis was reported as a serious adverse event in 6 semaglutide tablets -treated patients (0.1 events per 100 patient years) versus 1 in comparator-treated patients (<0.1 events per 100 patient years). Diabetic Retinopathy Complications : In the pool of placebo- and active-controlled trials with semaglutide tablets, patients reported diabetic retinopathy related adverse reactions during the trial (4.2% with semaglutide tablets and 3.8% with comparator). Hypoglycemia : Table 3 summarizes the incidence of hypoglycemia by various definitions in the placebo-controlled trials. Table 3. Hypoglycemia Adverse Reactions in Placebo-Controlled Trials in Patients with Type 2 Diabetes Mellitus Placebo Semaglutide Tablets 7 mg Semaglutide Tablets 14 mg Monotherapy (26 weeks) N=178 N=175 N=175 Severe* 0% 1% 0% Plasma glucose <54 mg/dL 1% 0% 0% Add-on to metformin and/or sulfonylurea, basal insulin alone or metformin in combination with basal insulin in patients with moderate renal impairment (26 weeks) N=161 - N=163 Severe* 0% - 0% Plasma glucose <54 mg/dL 3% - 6% Add-on to insulin with or without metformin (52 weeks) N=184 N=181 N=181 Severe* 1% 0% 1% Plasma glucose <54 mg/dL 32% 26% 30% * “Severe” hypoglycemia adverse reactions are episodes requiring the assistance of another person. Hypoglycemia was more frequent when semaglutide tablets were used in combination with insulin secretagogues (e.g., sulfonylureas) or insulin. Increases in Amylase and Lipase : In placebo-controlled trials, patients exposed to semaglutide tablets 7 mg and 14 mg tablets had a mean increase from baseline in amylase of 10% and 13%, respectively and lipase of 30% and 34%, respectively. These changes were not observed in placebo-treated patients. Cholelithiasis : In placebo-controlled trials to improve glycemic control, cholelithiasis was reported in 1% of patients treated with semaglutide tablets 7 mg. In a 4-year CV outcomes trial (Trial 7), cholelithiasis was reported in 1.1% of patients treated with semaglutide 14 mg tablets and in 0.9% of placebo-treated patients. In Trial 7, cholecystitis was reported in 1.1% of patients treated with semaglutide14 mg tablets and in 0.7% of placebo-treated patients. Increases in Heart Rate : In placebo-controlled trials, semaglutide tablets 7 mg and 14 mg tablets resulted in a mean increase in heart rate of 1 to 3 beats per minute. There was no change in heart rate in placebo-treated patients. 6.2 Postmarketing Experience The following adverse reactions have been reported during post-approval use of semaglutide, the active ingredient in RYBELSUS and OZEMPIC tablets. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. • Gastrointestinal : acute pancreatitis and necrotizing pancreatitis, sometimes resulting in death; ileus, intestinal obstruction, severe constipation including fecal impaction • Hypersensitivity : anaphylaxis, angioedema, rash, urticaria • Hepatobiliary : cholecystitis, cholelithiasis requiring cholecystectomy • Nervous system disorders : dizziness, dysesthesia, dysgeusia, headache • Pulmonary : Pulmonary aspiration has occurred in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation • Renal : acute kidney injury • Skin and Subcutaneous Tissue : alopecia

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, subcutaneous doses of 0.015, 0.075 and 0.15 mg/kg twice weekly (1.3-, 6.4- and 14-fold the MRHD) were administered from Gestation Day 16 to 140. Pharmacologically mediated marked initial maternal body weight loss and reductions in body weight gain and food consumption coincided with an increase in early pregnancy losses and led to delivery of slightly smaller offspring at ≥0.075 mg/kg twice weekly (≥6X human exposure). Salcaprozate sodium (SNAC), an absorption enhancer in RYBELSUS and OZEMPIC tablets, crosses the placenta and reaches fetal tissues in rats. In a pre- and postnatal development study in pregnant Sprague Dawley rats, SNAC was administered orally at 1,000 mg/kg/day (exposure levels were not measured) on Gestation Day 7 through Lactation Day 20. An increase in gestation length, an increase in the number of stillbirths and a decrease in pup viability were observed.