b'Bleed Size: 16Trim Size: 15.75WEGOVY (semaglutide) injection cemia (defined as a plasma glucose less than 54 mg/dL) was reported in 6.2% oftreatment as a result of adverse reactions. The most common adverse reactionsdose-escalation, more patients treated with WEGOVY, compared with placebo, had Rx Only WEGOVY-treated patients versus 2.5% of placebo-treated patients. One episode ofleading to discontinuation were nausea (1.8% versus 0.2%), vomiting (1.2% versusmaximum changes from baseline at any visit of 10 to 19 bpm (41% versus 34%, severe hypoglycemia (requiring the assistance of another person) was reported in0%), and diarrhea (0.7% versus 0.1%) for WEGOVY and placebo, respectively.respectively) and 20 bpm or more (26% versus 16%, respectively). Hypotension BRIEF SUMMARY: Please consult package insert for full prescribingone WEGOVY-treated patient versus no placebo-treated patients. Patients withAdverse reactions reported in greater than or equal to 2% of WEGOVY-treatedand Syncope: Adverse reactions related to hypotension (hypotension, orthostatic information. type 2 diabetes mellitus taking WEGOVY in combination with an insulin secreta- patients and more frequently than in placebo-treated patients are shown in Table 3. hypotension, and decreased blood pressure) were reported in 1.3% of WEGOVY-WARNING: RISK OF THYROID C-CELL TUMORS: In rodents, semaglutidegogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia,Table 3. Adverse Reactions Occurring in2% of WEGOVY-treatedtreated patients versus 0.4% of placebo-treated patients and syncope was reported causes dose-dependent and treatment-duration-dependent thyroidincluding severe hypoglycemia [see Adverse Reactions]. Hypoglycemia has beenPatients and More Frequently than with Placebo in 0.8% of WEGOVY-treated patients versus 0.2% of placebo-treated patients. C-cell tumors at clinically relevant exposures. It is unknown whetherobserved in patients treated with semaglutide at doses of 0.5 and 1 mg in combina-Some reactions were related to gastrointestinal adverse reactions and volume loss WEGOVY causes thyroid C-cell tumors, including medullary thyroidtion with insulin. The addition of WEGOVY in patients treated with insulin has notPlacebo WEGOVYNassociated with WEGOVY. Hypotension and orthostatic hypotension were more carcinoma (MTC), in humans as human relevance of semaglutide- been evaluated. Inform patients of the risk of hypoglycemia and educate them on theN = 1261= 2116frequently seen in patients on concomitant antihypertensive therapy. Appendicitis: induced rodent thyroid C-cell tumors has not been determined [seesigns and symptoms of hypoglycemia. In patients with type 2 diabetes, monitor% % Appendicitis (including perforated appendicitis) occurred in 10 (0.5%) WEGOVY-Warnings and Precautions]. WEGOVY is contraindicated in patientsblood glucose prior to starting WEGOVY and during WEGOVY treatment. WhenNausea 16 44 treated patients and 2 (0.2%) patients receiving placebo. Gastrointestinal Adverse with a personal or family history of MTC or in patients with Multipleinitiating WEGOVY, consider reducing the dose of concomitantly administeredDiarrhea 16 30 Reactions: In clinical trials, 73% of WEGOVY-treated patients and 47% of patients Endocrine Neoplasia syndrome type 2 (MEN 2) [see Contraindica- insulin secretagogue (such as sulfonylureas) or insulin to reduce the risk of hypogly- receiving placebo reported gastrointestinal disorders. The most frequently reported tions]. Counsel patients regarding the potential risk for MTC with thecemia [see Drug Interactions]. Acute Kidney Injury: There have been postmarketingVomiting 6 24 reactions were nausea (44% vs. 16%), vomiting (25% vs. 6%), and diarrhea (30% use of WEGOVYand inform them of symptoms of thyroid tumors (e.g.reports of acute kidney injury and worsening of chronic renal failure, which have invs. 16%). Other common reactions that occurred at a higher incidence amongConstipation 11 24 a mass in the neck, dysphagia, dyspnea, persistent hoarseness).some cases required hemodialysis, in patients treated with semaglutide. PatientsWEGOVY -treatedpatientsincludeddyspepsia,abdominalpain,abdominal Routine monitoring of serum calcitonin or using thyroid ultrasound iswith renal impairment may be at greater risk of acute kidney injury, but some of theseAbdominal Pain a 10 20 distension, eructation, flatulence, gastroesophageal reflux disease, gastritis, and of uncertain value for early detection of MTC in patients treated withevents have been reported in patients without known underlying renal disease. AHeadache 10 14 hemorrhoids. These reactions increased during dose escalation. Permanent discon-WEGOVY [see Contraindications and Warnings and Precautions]. majority of the reported events occurred in patients who had experienced nausea,b tinuation of treatment as a result of a gastrointestinal adverse reaction occurred vomiting, or diarrhea, leading to volume depletion [see Adverse Reactions]. MonitorFatigue 5 11 in 4.3% of WEGOVY-treated patients versus 0.7% of placebo-treated patients. INDICATIONS AND USAGE: WEGOVY is indicated as an adjunct to a reducedrenal function when initiating or escalating doses of WEGOVY in patients reportingDyspepsia 3 9 Injection Site Reactions: In clinical trials, 1.4% of WEGOVY-treated patients and calorie diet and increased physical activity for chronic weight management in adultssevere adverse gastrointestinal reactions. Monitor renal function in patients with1.0% of patients receiving placebo experienced injection site reactions (including with an initial body mass index (BMI) of 30 kg/m 2or greater (obesity) or 27 kg/ renal impairment reporting any adverse reactions that could lead to volume depletion.Dizziness 4 8 injection site pruritus, erythema, inflammation, induration, and irritation). Labo-m 2or greater (overweight) in the presence of at least one weight-related comorbidHypersensitivity: Serious hypersensitivity reactions (e.g., anaphylaxis, angio- Abdominal Distension 5 7 ratory Abnormalities: Patients treated with WEGOVY had a mean increase from condition (e.g., hypertension, type 2 diabetes mellitus, or dyslipidemia) Limitationedema) have been reported with semaglutide. If hypersensitivity reactions occur,baseline in amylase of 16% and lipase of 39%. These changes were not observed of Use: WEGOVY contains semaglutide and should not be coadministered withdiscontinue use of WEGOVY, treat promptly per standard of care, and monitor untilEructation1 7 in the placebo group. The clinical significance of elevations in lipase or amylase other semaglutide-containing products or with any other GLP-1 receptor agonist.signs and symptoms resolve. Do not use in patients with a previous hypersensitivityHypoglycemia in T2DM c 2 6 with WEGOVY is unknown in the absence of other signs and symptoms of The safety and effectiveness of WEGOVY in combination with other productsto semaglutide or any of the excipients in WEGOVY [see Contraindications].Flatulence 4 6 pancreatitis. Immunogenicity: Consistent with the potentially immunogenic prop-intended for weight loss, including prescription drugs, over-the-counter drugs, andAnaphylaxisandangioedemahavebeenreportedwithotherGLP-1receptorerties of protein and peptide pharmaceuticals, patients treated with WEGOVY may herbal preparations, have not been established. WEGOVY has not been studied inagonists. Use caution in a patient with a history of anaphylaxis or angioedema withGastroenteritis 4 6 develop anti-semaglutide antibodies. The detection of antibody formation is highly patients with a history of pancreatitis [see Warnings and Precautions]. another GLP-1 receptor agonist because it is unknown whether such patients will beGastroesophageal Reflux Disease 3 5 dependent on the sensitivity and specificity of the assay. Additionally, the observed CONTRAINDICATIONS: WEGOVY is contraindicated in the following conditions:predisposed to these reactions with WEGOVY. Diabetic Retinopathy Compli- Gastritis d 1 4 incidence of antibody (including neutralizing antibody) positivity in an assay may be cations in Patients with Type 2 Diabetes: In a trial of patients with type 2influenced by several factors including assay methodology, sample handling, timing A personal or family history of medullary thyroid carcinoma (MTC) or in patients2diabetes and BMI greater than or equal to 27 kg/m, diabetic retinopathy was reportedGastroenteritis Viral 3 4 of sample collection, concomitant medications, and underlying disease. For these with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) [see Warnings andPrecautions]. A prior serious hypersensitivity reaction to semaglutide or to any ofby 4.0% of WEGOVY -treated patients and 2.7% placebo-treated patients. In aHair Loss 1 3 reasons, the incidence of antibodies to semaglutide in the studies described below the excipients in WEGOVY. Serious hypersensitivity reactions, including anaphy- 2-year trial with semaglutide 0.5 mg and 1 mg once-weekly injection in patients witha Includes abdominal pain, abdominal pain upper, abdominal pain lower, gastrointestinal pain, abdominalcannot be directly compared with the incidence of antibodies in other studies or laxis and angioedema, have been reported with semaglutide[see Warnings andtype 2 diabetes and high cardiovascular risk, diabetic retinopathy complicationstenderness, abdominal discomfort and epigastric discomfortto other products. Across the clinical trials with antibody assessments, 50 (2.9%) Precautions]. (which was a 4-component adjudicated endpoint) occurred in patients treated withbIncludes fatigue and asthenia WEGOVY-treated patients developed anti-drug antibodies (ADAs) to the active semaglutideinjection(3.0%)comparedtoplacebo(1.8%).TheabsoluteriskcDefined as blood glucose 54 mg/dL with or without symptoms of hypoglycemia or severe hypogly- ingredient in WEGOVY (i.e., semaglutide). Of the 50 semaglutide-treated patientsWARNINGS AND PRECAUTIONS: Risk of Thyroid C-Cell Tumors: In mice andincrease for diabetic retinopathy complications was larger among patients with acemia (requiring the assistance of another person) in patients with type 2 diabetes not on concomitantthat developed semaglutide ADAs, 28 patients (1.6% of the total WEGOVY-treated rats, semaglutide caused a dose-dependent and treatment-duration-dependenthistory of diabetic retinopathy at baseline (semaglutide injection 8.2%, placeboinsulin (Study 2, WEGOVY N=403, Placebo N=402). See text below for further information regardingstudy population) developed antibodies cross-reacting with native GLP-1. The increase in the incidence of thyroid C-cell tumors (adenomas and carcinomas) afterhypoglycemia in patients with and without type 2 diabetes. T2DM = type 2 diabetes mellitusBleed Size:Trim Size:lifetime exposure at clinically relevant plasma exposures. It is unknown whether5.2%) than among patients without a known history of diabetic retinopathy (sema- dIncludes chronic gastritis, gastritis, gastritis erosive, and reflux gastritis in vitro neutralizing activity of the antibodies is uncertain at this time. Postmar-glutide injection 0.7%, placebo 0.4%). Rapid improvement in glucose control hasketing Experience: The following adverse reactions have been reported during 11 10.75 WEGOVY causes thyroid C-cell tumors, including medullary thyroid carcinomaAcute Pancreatitis: In WEGOVY clinical trials, acute pancreatitis was confirmed(MTC), in humans, as human relevance of semaglutide-induced rodent thyroidbeen associated with a temporary worsening of diabetic retinopathy. The effect ofby adjudication in 4 WEGOVY-treated patients (0.2 cases per 100 patient years)post-approval use of semaglutide, the active ingredient of WEGOVY. Because these C-cell tumors has not been determined. Cases of MTC in patients treated with lira - long-term glycemic control with semaglutide on diabetic retinopathy complicationsversus 1 in placebo-treated patients (less than 0.1 cases per 100 patient years).reactions are reported voluntarily from a population of uncertain size, it is not always glutide, another GLP-1 receptor agonist, have been reported in the postmarketinghas not been studied. Patients with a history of diabetic retinopathy should beOne additional case of acute pancreatitis was confirmed in a patient treated withpossible to reliably estimate their frequency or establish a causal relationship to drug period; the data in these reports are insufficient to establish or exclude a causalmonitored for progression of diabetic retinopathy. Heart Rate Increase: MeanWEGOVY in another clinical trial. Acute Gallbladder Disease: In WEGOVY clinicalexposure. Gastrointestinal Disorders: acute pancreatitis and necrotizing pancreatitis,increases in resting heart rate of 1 to 4 beats per minute (bpm) were observed in sometimes resulting in death; Hypersensitivity: anaphylaxis, angioedema, rash, relationship between MTC and GLP-1 receptor agonist use in humans. WEGOVYis trials, cholelithiasis was reported by 1.6% of WEGOVY-treated patients and 0.7% of WEGOVY -treated patients compared to placebo in clinical trials. More patients urticaria; Renal and Urinary Disorders: acute kidney injurycontraindicated in patients with a personal or family history of MTC or in patientstreated with WEGOVY compared with placebo had maximum changes from baselineplacebo-treated patients. Cholecystitis was reported by 0.6% of WEGOVY -treatedDRUG INTERACTIONS: Concomitant Use with an Insulin Secretagogue with MEN 2. Counsel patients regarding the potential risk for MTC with the use ofpatients and 0.2% of placebo-treated patients. Hypoglycemia: Patients with Type at any visit of 10 to 19 bpm (41% versus 34%, respectively) and 20 bpm or more(e.g., Sulfonylurea) or Insulin: WEGOVYlowers blood glucose and can cause WEGOVYand inform them of symptoms of thyroid tumors (e.g. a mass in the neck,2 Diabetes: In a trial of patients with type 2 diabetes and BMI greater than or equaldysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin(26% versus 16%, respectively). Monitor heart rate at regular intervals consistentto 27 kg/m 2 , clinically significant hypoglycemia (defined as a plasma glucose lesshypoglycemia. The risk of hypoglycemia is increased when WEGOVYis used in with usual clinical practice. Instruct patients to inform their healthcare providers of combination with insulin secretagogues (e.g., sulfonylureas) or insulin. The addition or using thyroid ultrasound is of uncertain value for early detection of MTC in than 54 mg/dL) was reported in 6.2% of WEGOVY -treated patients versus 2.5% palpitationsorfeelingsofaracingheartbeatwhileatrestduringWEGOVY of WEGOVYin patients treated with insulin has not been evaluated. When initiating patients treated with WEGOVY . Such monitoring may increase the risk of unneces- of placebo-treated patients. A higher rate of clinically significant hypoglycemictreatment. If patients experience a sustained increase in resting heart rate, discon-WEGOVY , consider reducing the dose of concomitantly administered insulin secre-sary procedures, due to the low test specificity for serum calcitonin and a hightinueWEGOVY.SuicidalBehaviorandIdeation:Suicidalbehaviorandepisodes was reported with WEGOVY(semaglutide 2.4 mg) versus semaglutide 1tagogue (such as sulfonylureas) or insulin to reduce the risk of hypoglycemia [see background incidence of thyroid disease. Significantly elevated serum calcitoninideation have been reported in clinical trials with other weight management products.mg (10.7 vs. 7.2 episodes per 100 patient years of exposure, respectively); the rateWarnings and Precautions and Adverse Reactions]. Oral Medications: WEGOVY value may indicate MTC and patients with MTC usually have calcitonin valuesMonitor patients treated with WEGOVY for the emergence or worsening of depres- in the placebo-treated group was 3.2 episodes per 100 patient years of exposure. Incauses a delay of gastric emptying and thereby has the potential to impact the greater than 50 ng/L. If serum calcitonin is measured and found to be elevated, theaddition, one episode of severe hypoglycemia requiring intravenous glucose was sion, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. absorption of concomitantly administered oral medications. In clinical pharma-patient should be further evaluated. Patients with thyroid nodules noted on physical reported in a WEGOVY -treated patient versus none in placebo-treated patients. The Discontinue WEGOVYin patients who experience suicidal thoughts or behaviors. cology trials with semaglutide 1 mg, semaglutide did not affect the absorption of examination or neck imaging should also be further evaluated. Acute pancre- Avoid WEGOVY in patients with a history of suicidal attempts or active suicidalrisk of hypoglycemia was increased when WEGOVYwas used with a sulfonylurea.orally administered medications. Nonetheless, monitor the effects of oral medica-atitis: Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizingPatients without Type 2 Diabetes: Episodes of hypoglycemia have been reported withpancreatitis, has been observed in patients treated with GLP-1 receptor agonists,ideation. GLP-1 receptor agonists in patients without type 2 diabetes mellitus. In WEGOVYtions concomitantly administered with WEGOVY .including semaglutide. Acute pancreatitis was observed in patients treated withADVERSE REACTIONS: The following serious adverse reactions are describedclinical trials in patients without type 2 diabetes mellitus, there was no systematicUSE IN SPECIFIC POPULATIONS: Pregnancy: Pregnancy Exposure Registry: WEGOVY in clinical trials [see Adverse Reactions]. After initiation of WEGOVY,below or elsewhere in the prescribing information: Risk of Thyroid C-Cell Tumorscapturing or reporting of hypoglycemia. Acute Kidney Injury: Acute kidney injuryThere will be a pregnancy exposure registry that monitors pregnancy outcomes in observe patients carefully for signs and symptoms of acute pancreatitis (including[see Warnings and Precautions]; Acute Pancreatitis [see Warnings and Precautions];occurred in clinical trials in 7 patients (0.4 cases per 100 patient years) receivingwomen exposed to semaglutide during pregnancy. Pregnant women exposed to persistent severe abdominal pain, sometimes radiating to the back, and which may orAcute Gallbladder Disease [see Warnings and Precautions]; Hypoglycemia [seeWEGOVY versus 4 patients (0.2 cases per 100 patient years of exposure) receivingWEGOVY and healthcare providers are encouraged to contact Novo Nordisk at may not be accompanied by vomiting). If acute pancreatitis is suspected, WEGOVY Warnings and Precautions]; Acute Kidney Injury [see Warnings and Precautions];placebo. Some of these adverse reactions occurred in association with gastrointes- 1-800-727-6500. Risk Summary: Based on animal reproduction studies, there may should promptly be discontinued and appropriate management should be initiated. IfHypersensitivity [see Warnings and Precautions]; Diabetic Retinopathy Complica- tinal adverse reactions or dehydration. In addition, 2 patients treated with WEGOVYbe potential risks to the fetus from exposure to semaglutide during pregnancy. Addi-acute pancreatitis is confirmed, WEGOVY should not be restarted. WEGOVY hastions in Patients with Type 2 Diabetes [see Warnings and Precautions]; Heart Ratehad acute kidney injury with dehydration in other clinical trials. The risk of renaltionally, weight loss offers no benefit to a pregnant patient and may cause fetal harm. not been studied in patients with a history of pancreatitis. It is unknown if patientsIncrease [see Warnings and Precautions]; Suicidal Behavior and Ideation[seeadverse reactions with WEGOVY was increased in patients with a history of renalWhen a pregnancy is recognized, advise the pregnant patient of the risk to a fetus, with a history of pancreatitis are at higher risk for development of pancreatitis onWarnings and Precautions]. Clinical Trials Experience: Because clinical trialsimpairment (trials included 65 patients with a history of moderate or severe renaland discontinue WEGOVY (see Clinical Considerations). Available pharmacovigi-WEGOVY. Acute Gallbladder Disease: In WEGOVY randomized clinical trials,are conducted under widely varying conditions, adverse reaction rates observed inimpairment at baseline), and occurred more frequently during dose titration. Retinallance data and data from clinical trials with WEGOVY use in pregnant patients are cholelithiasis was reported by 1.6% of WEGOVY-treated patients and 0.7% ofthe clinical trials of a drug cannot be directly compared to rates in the clinical studiesDisorders in Patients with Type 2 Diabetes: In a trial of patients with type 2 diabetesinsufficient to establish a drug-associated risk of major birth defects, miscarriage placebo-treated patients. Cholecystitis was reported by 0.6% of WEGOVY-treatedof another drug and may not reflect the rates observed in practice. WEGOVY wasand BMI greater than or equal to 27 kg/m, retinal disorders were reported by 6.9% ofor adverse maternal or fetal outcomes. In pregnant rats administered semaglutide 2patients and 0.2% of placebo-treated patients. Substantial or rapid weight loss canevaluated for safety in 3 randomized, double-blind, placebo-controlled trials thatpatients treated with WEGOVY (semaglutide 2.4 mg), 6.2% of patients treated withduring organogenesis, embryofetal mortality, structural abnormalities and altera-increase the risk of cholelithiasis; however, the incidence of acute gallbladderincluded 2116 patients with overweight or obesity treated with WEGOVY for up tosemaglutide 1 mg, and 4.2% of patients treated with placebo. The majority of eventstions to growth occurred at maternal exposures below the maximum recommended disease was greater in WEGOVY-treated patients than in placebo-treated patients,68 weeks and a 7 week off drug follow-up period. Baseline characteristics includedwere reported as diabetic retinopathy (4.0%, 2.7%, and 2.7%, respectively) andhuman dose (MRHD) based on AUC. In rabbits and cynomolgus monkeys admin-even after accounting for the degree of weight loss. If cholelithiasis is suspected,a mean age of 48 years, 71% women, 72% White, 42% with hypertension, 19%non-proliferative retinopathy (0.7%, 0%, and 0%, respectively). Increase in Heartistered semaglutide during organogenesis, early pregnancy losses and structural gallbladder studies and appropriate clinical follow-up are indicated. Hypogly- with type 2 diabetes, 43% with dyslipidemia, 28% with a BMI greater than 40 kg/ Rate: Mean increases in resting heart rate of 1 to 4 beats per minute (bpm) wereabnormalities were observed at below the MRHD (rabbit) and greater than or equal to cemia: WEGOVY lowers blood glucose and can cause hypoglycemia. In a trial ofm 2 , and 4% with cardiovascular disease. In clinical trials, 6.8% of patients treatedobserved with routine clinical monitoring in WEGOVY-treated patients compared2-fold the MRHD (monkey). These findings coincided with a marked maternal body patients with type 2 diabetes and BMI greater than or equal to 27 kg/m 2 , hypogly- with WEGOVY and 3.2% of patients treated with placebo permanently discontinuedto placebo in clinical trials. In trials in which patients were randomized prior toweight loss in both animal species (see Data). The estimated background risk of'