b'WEGOVY (semaglutide) injection a trial of patients with type 2 diabetes and BMI greater than or equal to 27 kg/m 2 ,WEGOVY and 3.2% of patients treated with placebo permanently discontinuedcompared to placebo in clinical trials. In trials in which patients were randomized prior Rx Only hypoglycemia (defined as a plasma glucose less than 54 mg/dL) was reported intreatment as a result of adverse reactions. The most common adverse reactionsto dose-escalation, more patients treated with WEGOVY, compared with placebo, BRIEF SUMMARY: Please consult package insert for full prescribing6.2% of WEGOVY-treated patients versus 2.5% of placebo-treated patients. Oneleading to discontinuation were nausea (1.8% versus 0.2%), vomiting (1.2% versushad maximum changes from baseline at any visit of 10 to 19 bpm (41% versus 34%, information. episode of severe hypoglycemia (requiring the assistance of another person) was0%), and diarrhea (0.7% versus 0.1%) for WEGOVY and placebo, respectively.respectively) and 20 bpm or more (26% versus 16%, respectively). Hypotension reported in one WEGOVY-treated patient versus no placebo-treated patients.Adverse reactions reported in greater than or equal to 2% of WEGOVY-treatedand Syncope: Adverse reactions related to hypotension (hypotension, orthostatic WARNING: RISK OF THYROID C-CELL TUMORS: In rodents, semaglu- Patients with type 2 diabetes mellitus taking WEGOVY in combination with anpatients 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-tidecausesdose-dependentandtreatment-duration-dependentinsulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk ofTable 3. Adverse Reactions Occurring in2% of WEGOVY-treatedtreated patients versus 0.4% of placebo-treated patients and syncope was reported thyroid C-cell tumors at clinically relevant exposures. It is unknownhypoglycemia, including severe hypoglycemia [see Adverse Reactions]. Hypogly- Patients and More Frequently than with Placebo in 0.8% of WEGOVY-treated patients versus 0.2% of placebo-treated patients. whetherWEGOVYcausesthyroidC-celltumors,includingcemia has been observed in patients treated with semaglutide at doses of 0.5 and 1Some reactions were related to gastrointestinal adverse reactions and volume loss medullary thyroid carcinoma (MTC), in humans as human relevancemg in combination with insulin. The addition of WEGOVY in patients treated withPlacebo WEGOVYassociated with WEGOVY. Hypotension and orthostatic hypotension were more of semaglutide-induced rodent thyroid C-cell tumors has not beeninsulin has not been evaluated. Inform patients of the risk of hypoglycemia andN = 1261N = 2116frequently seen in patients on concomitant antihypertensive therapy. Appendicitis: determined [see Warnings and Precautions]. WEGOVY is contra- educate them on the signs and symptoms of hypoglycemia. In patients with type 2% % Appendicitis (including perforated appendicitis) occurred in 10 (0.5%) WEGOVY-indicated in patients with a personal or family history of MTC or indiabetes, monitor blood glucose prior to starting WEGOVY and during WEGOVYNausea 16 44 treated patients and 2 (0.2%) patients receiving placebo. Gastrointestinal Adverse patients with Multiple Endocrine Neoplasia syndrome type 2 (MENtreatment. When initiating WEGOVY, consider reducing the dose of concomitantlyDiarrhea 16 30 Reactions: In clinical trials, 73% of WEGOVY-treated patients and 47% of patients 2) [see Contraindications]. Counsel patients regarding the potentialadministered insulin secretagogue (such as sulfonylureas) or insulin to reduce thereceiving placebo reported gastrointestinal disorders. The most frequently reported risk for MTC with the use of WEGOVY and inform them of symptomsrisk of hypoglycemia [see Drug Interactions]. Acute Kidney Injury: There haveVomiting 6 24 reactions were nausea (44% vs. 16%), vomiting (25% vs. 6%), and diarrhea (30% of thyroid tumors (e.g. a mass in the neck, dysphagia, dyspnea,been postmarketing reports of acute kidney injury and worsening of chronic renalConstipation 11 24 vs. 16%). Other common reactions that occurred at a higher incidence among persistent hoarseness). Routine monitoring of serum calcitonin orfailure, which have in some cases required hemodialysis, in patients treated withWEGOVY-treatedpatientsincludeddyspepsia,abdominalpain,abdominal using thyroid ultrasound is of uncertain value for early detection ofsemaglutide. Patients with renal impairment may be at greater risk of acute kidneyAbdominal Pain a 10 20 distension, eructation, flatulence, gastroesophageal reflux disease, gastritis, and MTC in patients treated with WEGOVY [see Contraindications andinjury, but some of these events have been reported in patients without known unde-r Headache 10 14 hemorrhoids. These reactions increased during dose escalation. Permanent discon-Warnings and Precautions]. lying renal disease. A majority of the reported events occurred in patients who hadFatigue b 5 11 tinuation of treatment as a result of a gastrointestinal adverse reaction occurred experienced nausea, vomiting, or diarrhea, leading to volume depletion [see Adversein 4.3% of WEGOVY-treated patients versus 0.7% of placebo-treated patients. INDICATIONS AND USAGE: WEGOVY is indicated as an adjunct to a reducedReactions]. Monitor renal function when initiating or escalating doses of WEGOVYDyspepsia 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 adultsinpatientsreportingsevereadversegastrointestinalreactions.Monitorrenal1.0% 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/ function in patients with renal impairment reporting any adverse reactions that couldDizziness 4 8 injection site pruritus, erythema, inflammation, induration, and irritation).Labora-m 2or greater (overweight) in the presence of at least one weight-related comorbidlead to volume depletion. Hypersensitivity: Serious hypersensitivity reactionsAbdominal Distension 5 7 tory Abnormalities: Patients treated with WEGOVY had a mean increase from condition (e.g., hypertension, type 2 diabetes mellitus, or dyslipidemia) Limitation(e.g., anaphylaxis, angioedema) have been reported with semaglutide. If hypersens-i Eructation1 7 baseline in amylase of 16% and lipase of 39%. These changes were not observed of Use: WEGOVY contains semaglutide and should not be coadministered withtivity reactions occur, discontinue use of WEGOVY, treat promptly per standard ofHypoglycemia in T2DM c 2 6 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.care, and monitor until signs and symptoms resolve. Do not use in patients with awith WEGOVY is unknown in the absence of other signs and symptoms of The safety and effectiveness of WEGOVY in combination with other productsprevious hypersensitivity to semaglutide or any of the excipients in WEGOVY [seeFlatulence 4 6 pancreatitis. Immunogenicity: Consistent with the potentially immunogenic prop-intended for weight loss, including prescription drugs, over-the-counter drugs, andContraindications]. Anaphylaxis and angioedema have been reported with otherGastroenteritis 4 6 erties of protein and peptide pharmaceuticals, patients treated with WEGOVY may herbal preparations, have not been established. WEGOVY has not been studied inGLP-1 receptor agonists. Use caution in a patient with a history of anaphylaxis ordevelop anti-semaglutide antibodies. The detection of antibody formation is highly patients with a history of pancreatitis [see Warnings and Precautions]. angioedema with another GLP-1 receptor agonist because it is unknown whetherGastroesophageal Reflux Disease 3 5 dependent on the sensitivity and specificity of the assay. Additionally, the observed CONTRAINDICATIONS: WEGOVY is contraindicated in the following conditions:such patients will be predisposed to these reactions with WEGOVY. DiabeticGastritis d 1 4 incidence of antibody (including neutralizing antibody) positivity in an assay may be A personal or family history of medullary thyroid carcinoma (MTC) or in patientsRetinopathy Complications in Patients with Type 2 Diabetes: In a trial ofinfluenced by several factors including assay methodology, sample handling, timing with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) [see Warnings andpatients with type 2 diabetes and BMI greater than or equal to 27 kg/m 2 , diabeticGastroenteritis Viral 3 4 of sample collection, concomitant medications, and underlying disease. For these Precautions]. A prior serious hypersensitivity reaction to semaglutide or to any ofretinopathy was reported by 4.0% of WEGOVY-treated patients and 2.7% placebo- Hair Loss 1 3 reasons, the incidence of antibodies to semaglutide in the studies described below treated patients. In a 2-year trial with semaglutide 0.5 mg and 1 mg once-weeklyacannot be directly compared with the incidence of antibodies in other studies or the excipients in WEGOVY. Serious hypersensitivity reactions, including anaphy- Includes abdominal pain, abdominal pain upper, abdominal pain lower, gastrointestinal pain, abdominal laxis and angioedema, have been reported with semaglutide[see Warnings andinjection in patients with type 2 diabetes and high cardiovascular risk, diabetic reti- tenderness, abdominal discomfort and epigastric discomfortto other products. Across the clinical trials with antibody assessments, 50 (2.9%) Precautions]. nopathy complications (which was a 4-component adjudicated endpoint) occurredb Includes fatigue and asthenia WEGOVY-treated patients developed anti-drug antibodies (ADAs) to the active in patients treated with semaglutide injection (3.0%) compared to placebo (1.8%).c Defined 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 andThe absolute risk increase for diabetic retinopathy complications was larger amongcemia (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-dependentpatients with a history of diabetic retinopathy at baseline (semaglutide injectioninsulin (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 in increase in the incidence of thyroid C-cell tumors (adenomas and carcinomas) after8.2%, placebo 5.2%) than among patients without a known history of diabetic reti- d hypoglycemia in patients with and without type 2 diabetes. T2DM = type 2 diabetes mellitus vitro neutralizing activity of the antibodies is uncertain at this time. Postmarketing lifetime exposure at clinically relevant plasma exposures. It is unknown whethernopathy (semaglutide injection 0.7%, placebo 0.4%). Rapid improvement in glucoseIncludes chronic gastritis, gastritis, gastritis erosive, and reflux gastritis Experience: The following adverse reactions have been reported during post-WEGOVY causes thyroid C-cell tumors, including medullary thyroid carcinomacontrol has been associated with a temporary worsening of diabetic retinopathy. TheAcute Pancreatitis: In WEGOVY clinical trials, acute pancreatitis was confirmedapproval use of semaglutide, the active ingredient of WEGOVY. Because these (MTC), in humans, as human relevance of semaglutide-induced rodent thyroideffectoflong-termglycemiccontrolwithsemaglutideondiabeticretinopathyby adjudication in 4 WEGOVY-treated patients (0.2 cases per 100 patient years)reactions are reported voluntarily from a population of uncertain size, it is not always C-cell tumors has not been determined. Cases of MTC in patients treated with lira - complications has not been studied. Patients with a history of diabetic retinopathyversus 1 in placebo-treated patients (less than 0.1 cases per 100 patient years).possible to reliably estimate their frequency or establish a causal relationship to drug glutide, another GLP-1 receptor agonist, have been reported in the postmarketingshould be monitored for progression of diabetic retinopathy. Heart Rate Increase:One additional case of acute pancreatitis was confirmed in a patient treated withexposure. Gastrointestinal Disorders: acute pancreatitis and necrotizing pancreatitis, period; the data in these reports are insufficient to establish or exclude a causalMean increases in resting heart rate of 1 to 4 beats per minute (bpm) were observedWEGOVY in another clinical trial. Acute Gallbladder Disease: In WEGOVY clinicalsometimes resulting in death; Hypersensitivity: anaphylaxis, angioedema, rash, relationship between MTC and GLP-1 receptor agonist use in humans. WEGOVYin WEGOVY-treated patients compared to placebo in clinical trials. More patientstrials, cholelithiasis was reported by 1.6% of WEGOVY-treated patients and 0.7%urticaria; Renal and Urinary Disorders: acute kidney injuryis contraindicated in patients with a personal or family history of MTC or in patientstreatedwithWEGOVYcomparedwithplacebohadmaximumchangesfromof placebo-treated patients. Cholecystitis was reported by 0.6% of WEGOVY- DRUG INTERACTIONS: Concomitant Use with an Insulin Secretagogue with MEN 2. Counsel patients regarding the potential risk for MTC with the use ofbaseline at any visit of 10 to 19 bpm (41% versus 34%, respectively) and 20 bpm ortreated patients and 0.2% of placebo-treated patients. Hypoglycemia: Patients with(e.g., Sulfonylurea) or Insulin: WEGOVY lowers blood glucose and can cause WEGOVY and inform them of symptoms of thyroid tumors (e.g. a mass in the neck,Type 2 Diabetes: In a trial of patients with type 2 diabetes and BMI greater than or dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitoninmore (26% versus 16%, respectively). Monitor heart rate at regular intervals consis- equal to 27 kg/m 2 , clinically significant hypoglycemia (defined as a plasma glucosehypoglycemia. The risk of hypoglycemia is increased when WEGOVY is used in or using thyroid ultrasound is of uncertain value for early detection of MTC intent with usual clinical practice. Instruct patients to inform their healthcare providersless than 54 mg/dL) was reported in 6.2% of WEGOVY-treated patients versuscombination with insulin secretagogues (e.g., sulfonylureas) or insulin. The addition patients treated with WEGOVY. Such monitoring may increase the risk of unneces- of palpitations or feelings of a racing heartbeat while at rest during WEGOVY2.5% of placebo-treated patients. A higher rate of clinically significant hypoglycemicof WEGOVY in patients treated with insulin has not been evaluated. When initi-sary procedures, due to the low test specificity for serum calcitonin and a hightreatment. If patients experience a sustained increase in resting heart rate, discon- episodes was reported with WEGOVY (semaglutide 2.4 mg) versus semaglutide 1ating WEGOVY, consider reducing the dose of concomitantly administered insulin background incidence of thyroid disease. Significantly elevated serum calcitonintinueWEGOVY. SuicidalBehaviorandIdeation:Suicidalbehaviorandmg (10.7 vs. 7.2 episodes per 100 patient years of exposure, respectively); the ratesecretagogue (such as sulfonylureas) or insulin to reduce the risk of hypoglycemia value may indicate MTC and patients with MTC usually have calcitonin valuesideation have been reported in clinical trials with other weight management products.in the placebo-treated group was 3.2 episodes per 100 patient years of exposure. In[seeWarningsandPrecautionsandAdverseReactions].OralMedications: greater than 50 ng/L. If serum calcitonin is measured and found to be elevated, theMonitor patients treated with WEGOVY for the emergence or worsening of depres- addition, one episode of severe hypoglycemia requiring intravenous glucose wasWEGOVY causes a delay of gastric emptying and thereby has the potential to patient should be further evaluated. Patients with thyroid nodules noted on physicalsion, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.reported in a WEGOVY-treated patient versus none in placebo-treated patients.impact the absorption of concomitantly administered oral medications. In clinical examination or neck imaging should also be further evaluated. Acute pancre- Discontinue WEGOVY in patients who experience suicidal thoughts or behaviors.The risk of hypoglycemia was increased when WEGOVY was used with a sulfo- pharmacology trials with semaglutide 1 mg, semaglutide did not affect the absorp-atitis: Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizingAvoid WEGOVY in patients with a history of suicidal attempts or active suicidalnylurea. Patients without Type 2 Diabetes: Episodes of hypoglycemia have beention of orally administered medications. Nonetheless, monitor the effects of oral pancreatitis, has been observed in patients treated with GLP-1 receptor agonists,ideation. reported with GLP-1 receptor agonists in patients without type 2 diabetes mellitus.medications concomitantly administered with WEGOVY.including semaglutide. Acute pancreatitis was observed in patients treated withADVERSE REACTIONS: The following serious adverse reactions are describedIn WEGOVY clinical trials in patients without type 2 diabetes mellitus, there wasUSE 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 Tumorsno systematic capturing or reporting of hypoglycemia. Acute Kidney Injury: AcuteThere 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];kidney injury occurred in clinical trials in 7 patients (0.4 cases per 100 patient years)women 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 [seereceiving WEGOVY versus 4 patients (0.2 cases per 100 patient years of exposure)WEGOVY and healthcare providers are encouraged to contact Novo Nordisk at may not be accompanied by vomiting). If acute pancreatitis is suspected, WEGOVYWarnings and Precautions]; Acute Kidney Injury [see Warnings and Precautions];receiving placebo. Some of these adverse reactions occurred in association with1-800-727-6500. 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- gastrointestinal adverse reactions or dehydration. In addition, 2 patients treatedbe 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 Ratewith WEGOVY had acute kidney injury with dehydration in other clinical trials.tionally, 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[seeWarningsandPrecautions]; SuicidalBehaviorandIdeation[seeThe risk of renal adverse reactions with WEGOVY was increased in patients withWhen 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 trialsa history of renal impairment (trials included 65 patients with a history of moderateand discontinue WEGOVY (see Clinical Considerations). Available pharmacovigi-WEGOVY. Acute Gallbladder Disease: In WEGOVY randomized clinicalare conducted under widely varying conditions, adverse reaction rates observed inor severe renal impairment at baseline), and occurred more frequently during doselance data and data from clinical trials with WEGOVY use in pregnant patients are trials, cholelithiasis was reported by 1.6% of WEGOVY-treated patients and 0.7%the clinical trials of a drug cannot be directly compared to rates in the clinical studiestitration. Retinal Disorders in Patients with Type 2 Diabetes: In a trial of patients withinsufficient to establish a drug-associated risk of major birth defects, miscarriage of placebo-treated patients. Cholecystitis was reported by 0.6% of WEGOVY- of another drug and may not reflect the rates observed in practice. WEGOVY wastype 2 diabetes and BMI greater than or equal to 27 kg/m 2 , retinal disorders wereor adverse maternal or fetal outcomes. In pregnant rats administered semaglutide treated patients and 0.2% of placebo-treated patients. Substantial or rapid weightevaluated for safety in 3 randomized, double-blind, placebo-controlled trials thatreported by 6.9% of patients treated with WEGOVY (semaglutide 2.4 mg), 6.2% ofduring organogenesis, embryofetal mortality, structural abnormalities and altera-loss can increase the risk of cholelithiasis; however, the incidence of acute gall- included 2116 patients with overweight or obesity treated with WEGOVY for up topatients treated with semaglutide 1 mg, and 4.2% of patients treated with placebo.tions to growth occurred at maternal exposures below the maximum recommended bladder disease was greater in WEGOVY-treated patients than in placebo-treated68 weeks and a 7 week off drug follow-up period. Baseline characteristics includedThe majority of events were reported as diabetic retinopathy (4.0%, 2.7%, and 2.7%,human dose (MRHD) based on AUC. In rabbits and cynomolgus monkeys admin-patients, even after accounting for the degree of weight loss. If cholelithiasis isa mean age of 48 years, 71% women, 72% White, 42% with hypertension, 19% withrespectively) and non-proliferative retinopathy (0.7%, 0%, and 0%, respectively).istered semaglutide during organogenesis, early pregnancy losses and structural suspected, gallbladder studies and appropriate clinical follow-up are indicated.type 2 diabetes, 43% with dyslipidemia, 28% with a BMI greater than 40 kg/m 2 ,Increase in Heart Rate: Mean increases in resting heart rate of 1 to 4 beats per minuteabnormalities were observed at below the MRHD (rabbit) and greater than or equal to Hypoglycemia: WEGOVY lowers blood glucose and can cause hypoglycemia. Inand 4% with cardiovascular disease. In clinical trials, 6.8% of patients treated with(bpm) were observed with routine clinical monitoring in WEGOVY-treated patients2-fold the MRHD (monkey). These findings coincided with a marked maternal body'