b'26AVAILABLE ONTHE FIRST AND ONLY UNIFORM FORMULARY ORAL GLP-1 RAFor adults with type 2 diabetesTo learn more, visit RYBELSUSpro.comGLP-1 RA=glucagon-like peptide-1 receptor agonist.In separate head-to-head studies1,a,b No dosage adjustment recommended for 1 : Superior A1C reductions vs both Januviaand Jardiance26-WEEK PRIMARY ENDPOINT \x7f Patients aged 65 years No overall differences in safety or ef cacy were detected between these patients and younger patients, but greater RYBELSUS vs Januvia (P0.001 for both comparisons) RYBELSUS vs Jardiance (P0.001) sensitivity of some older individuals cannot be ruled out -1.3% -1.0% -0.8%-1.3%-0.9%\x7f Hepatic impairment In a study in subjects with different degrees of hepatic impairment, no clinically relevant change in semaglutide with RYBELSUS 14 mgwith RYBELSUS 7 mgwith Januvia 100 mgwith RYBELSUS 14 mg with Jardiance 25 mg pharmacokinetics (PK) was observed (Baseline: 8.3%)(Baseline: 8.4%) (Baseline: 8.3%)(Baseline: 8.1%)(Baseline: 8.1%) \x7f Renal impairmentStudy Designs In patients with renal impairment, including end-stage renal disease (ESRD), no clinically relevant change in semaglutide aPK was observedPIONEER 3: Head-to-head vs Januvia In a double-blind, double-dummy trial with a primary endpoint of mean change in A1C from baseline to 26 weeks, 1864 patients with type 2 diabetes on metformin alone or metformin with a sulfonylurea were randomized to RYBELSUS 3 mg (n=466),There have been postmarketing reports of acute kidney injury and worsening of chronic renal failure, which may sometimes RYBELSUS 7 mg (n=465), RYBELSUS 14 mg (n=465), or Januvia 100 mg (n=467), all once daily.1,2 require hemodialysis, in patients treated with GLP-1 receptor agonists, including semaglutide. Monitor renal function when b In an open-label trial with a primary endpoint of mean change in A1C from baseline to 26 weeks, 822initiating or escalating doses of RYBELSUS in patients reporting severe adverse gastrointestinal reactions. Please see Acute PIONEER 2: Head-to-head vs Jardiancepatients with type 2 diabetes on metformin were randomized to RYBELSUS 14 mg (n=411) or Jardiance 25 mg (n=410), both once daily.1,3 Kidney Injury warning below.Indications and Usage Contraindications Warnings and Precautions (continued)RYBELSUS delays gastric emptying and has the potential to impact the absorption RYBELSUS (semaglutide) tablets 7 mg or 14 mg is indicated as an adjunct to diet and RYBELSUS is contraindicated in patients with a personal or family history of medullary\x7f Hypoglycemia:The risk of hypoglycemia is increased when RYBELSUS is used inof other oral medications. Closely follow RYBELSUS administration instructions when exercise to improve glycemic control in adults with type 2 diabetes. thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndromecombination with insulin secretagogues (e.g., sulfonylureas) or insulin. Patients may require acoadministering with other oral medications and consider increased monitoring for type 2 (MEN 2), and in patients with known hypersensitivity to semaglutide or to anylower dose of the secretagogue or insulin to reduce the risk of hypoglycemia in this setting medications with a narrow therapeutic index, such as levothyroxineLimitations of Use \x7f RYBELSUS is not recommended as arst-line therapy for patients who haveof the components in RYBELSUS \x7f Acute Kidney Injury:There have been postmarketing reports of acute kidney injuryUse in Speci c Populationsinadequate glycemic control on diet and exercise because of the uncertain relevance ofWarnings and Precautions and worsening of chronic renal failure, which may sometimes require hemodialysis, Pregnancy: Available data with RYBELSUS are not suf cient to determine a drug-associated rodent C-cell tumorndings to humans \x7f Risk of Thyroid C-Cell Tumors: Patients should be further evaluated if serumin patients treated with GLP-1 receptor agonists, including semaglutide. Some ofrisk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Based on \x7fRYBELSUS has not been studied in patients with a history of pancreatitis. Considercalcitonin is measured and found to be elevated or thyroid nodules are noted onthese events have been reported in patients without known underlying renal disease.animal reproduction studies, there may be risks to the fetus from exposure to RYBELSUS. Use other antidiabetic therapies in patients with a history of pancreatitis physical examination or neck imaging A majority of the reported events occurred in patients who had experienced nausea,only if the potential bene t justi es the potential risk to the fetusvomiting, diarrhea, or dehydration. Monitor renal function when initiating or escalating Lactation: There are no data on the presence of semaglutide in human milk, the effects \x7fRYBELSUSis not indicated for use in patients with type 1 diabetes or for the\x7fPancreatitis: Has been reported in clinical trials. Observe patients carefully fortreatment of patients with diabetic ketoacidosis signs and symptoms of pancreatitis (including persistent severe abdominal pain,doses of RYBELSUSin patients reporting severe adverse gastrointestinal reactions on the breastfed infant, or the effects on milk production. Because of the unknown sometimes radiating to the back and which may or may not be accompanied by\x7fHypersensitivity:Serious hypersensitivity reactions (e.g., anaphylaxis, potential for serious adverse reactions in the breastfed infant due to the possible Important Safety Information vomiting). If pancreatitis is suspected, discontinue RYBELSUS and initiate appropriateangioedema) have been reported with GLP-1 receptor agonists, including semaglutide.accumulation of salcaprozate sodium (SNAC), an absorption enhancer in RYBELSUS, management; if con rmed, do not restart RYBELSUS If hypersensitivity reactions occur, discontinue use of RYBELSUS, treat promptly perfrom breastfeeding and because there are alternative formulations of semaglutide that WARNING: RISK OF THYROID C-CELL TUMORS \x7f Diabetic Retinopathy Complications: In a pooled analysis of glycemic controlstandard of care, and monitor until signs and symptoms resolve. Use caution in a patientcan be used during lactation, advise patients that breastfeeding is not recommended \x7fIn rodents, semaglutide causes dose-dependent and treatment- trials with RYBELSUS, patients reported diabetic retinopathy related adversewith a history of angioedema or anaphylaxis with another GLP-1 receptor agonist during treatment with RYBELSUSduration-dependent thyroid C-cell tumors at clinically relevant exposures.reactions during the trial (4.2% with RYBELSUS and 3.8% with comparator). In aAdverse ReactionsDiscontinue RYBELSUS in women at least 2 months before a planned pregnancy due to It is unknown whether RYBELSUS causes thyroid C-cell tumors, including2-year trial with semaglutide injection involving patients with type 2 diabetes and The most common adverse reactions, reported in 5% of patients treated with RYBELSUS the long washout period for semaglutidemedullary thyroid carcinoma (MTC), in humans as human relevance ofhigh cardiovascular risk, more events of diabetic retinopathy complications occurredare nausea, abdominal pain, diarrhea, decreased appetite, vomiting and constipationPediatric Use: Safety and ef cacy of RYBELSUS have not been established in pediatric semaglutide-induced rodent thyroid C-cell tumors has not been determined in patients treated with semaglutide injection (3.0%) compared to placebo (1.8%).Drug Interactions patients (younger than 18 years)\x7f R YBELSUS is contraindicated in patients with a personal or family historyThe absolute risk increase for diabetic retinopathy complications was larger among The risk of hypoglycemia may be lowered by a reduction in the dose of concomitantly of MTC and in patients with Multiple Endocrine Neoplasia syndrome typepatients with a history of diabetic retinopathy at baseline than among patients withoutadministered secretagogues or insulin Please see Brief Summary of Prescribing Information, 2 (MEN 2). Counsel patients regarding the potential risk for MTC with thea known history of diabetic retinopathy. including Boxed Warning, on next page.use of RYBELSUS and inform them of symptoms of thyroid tumors (e.g.Rapid improvement in glucose control has been associated with a temporary a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routineworsening of diabetic retinopathy. Patients with a history of diabetic retinopathyReferences: 1. RYBELSUS [package insert]. Plainsboro, NJ: Novo Nordisk Inc; January monitoring of serum calcitonin or using thyroid ultrasound is of uncertainshould be monitored for progression of diabetic retinopathy 2020. 2. Rosenstock J, Allison D, Birkenfeld AL, et al. Effect of additional oral semaglutide value for early detection of MTC in patients treated with RYBELSUSvs sitagliptin on glycated hemoglobin in adults with type 2 diabetes uncontrolled with RYBELSUSis a registered trademark of Novo Nordisk A/S. metformin alone or with sulfonylurea: the PIONEER 3 randomized clinical trial. JAMA. Novo Nordiskis a registered trademark of Novo Nordisk A/S. 2019;321(15):1466-1480. 3. Rodbard HW, Rosenstock J, Canani LH, et al. Oral semaglutide All other trademarks, registered or unregistered, are the property of their respective owners. versus empagli ozin in patients with type 2 diabetes uncontrolled on metformin: the2020 Novo NordiskPrinted in the U.S.A.US20RYB00334May 2020 PIONEER 2 trial. Diabetes Care. 2019;42(12):2272-2281.'