HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the informationneeded to use WEGOVY® safely and effectively. See
full prescribing information for WEGOVY®.
WEGOVY® (semaglutide) injection, for subcutaneoususe
Initial U.S. Approval: 2017
WARNING: RISK OF THYROID C−CELL TUMORS
See full prescribing information for complete
boxed warning.
• In rodents, semaglutide causes thyroid C-celltumors at clinically relevant exposures. It is
unknown whether WEGOVY® causes thyroid C-celltumors, including medullary thyroid carcinoma(MTC), in humans as the human relevance ofsemaglutide-induced rodent thyroid C-cell tumors
has not been determined (5.1, 13.1).
• WEGOVY® is contraindicated in patients with apersonal or family history of MTC or in patientswith Multiple Endocrine Neoplasia syndrome
type 2 (MEN 2). Counsel patients regarding thepotential risk of MTC and symptoms of thyroid
tumors (4, 5.1).
——— RECENT MAJOR CHANGES ———Indications and Usage (1).................................................03/2024
Dosing and Administration (2.2)...................................... 07/2023
Warnings and Precaution, Hypoglycemia (5.4)...............03/2024——— INDICATIONS AND USAGE ———WEGOVY® is a glucagon-like peptide-1 (GLP-1) receptor
agonist indicated in combination with a reduced calorie diet andincreased physical activity:• to reduce the risk of major adverse cardiovascular events(cardiovascular death, non-fatal myocardial infarction, or
non-fatal stroke) in adults with established cardiovasculardisease and either obesity or overweight (1).
• to reduce excess body weight and maintain weight reduction
long term in:• Adults and pediatric patients aged 12 years and older withobesity• Adults with overweight in the presence of at least one
weight-related comorbid condition (1).

FULL PRESCRIBING INFORMATION: CONTENTS*
WARNING: RISK OF THYROID C−CELL TUMORS
1
INDICATIONS AND USAGE
2
DOSAGE AND ADMINISTRATION
2.1	Important Monitoring and Administration
Instructions
2.2 Recommended Dosage in Adults
2.3	Recommended Dosage in Pediatric Patients Aged
12 Years and Older
2.4 Recommendations Regarding Missed Dose3
DOSAGE FORMS AND STRENGTHS
4CONTRAINDICATIONS5WARNINGS AND PRECAUTIONS
5.1 Risk of Thyroid C-Cell Tumors
5.2 Acute Pancreatitis
5.3	Acute Gallbladder Disease
5.4	Hypoglycemia
5.5	Acute Kidney Injury
5.6	Hypersensitivity Reactions
5.7	Diabetic Retinopathy Complications in Patients withType 2 Diabetes

Limitations of Use:• Coadministration with other semaglutide-containing products
or with any other GLP-1 receptor agonist is not recommended(1).
——— DOSAGE AND ADMINISTRATION ———• Administer WEGOVY® once weekly as an adjunct to diet andincreased physical activity, on the same day each week, at any
time of day, with or without meals (2.1).
• Inject subcutaneously in the abdomen, thigh or upper arm(2.1).
• In patients with type 2 diabetes, monitor blood glucose prior
to starting and during WEGOVY® treatment (2.1).
• Initiate at 0.25 mg once weekly for 4 weeks. Then follow the
dosage escalation schedule, titrating every 4 weeks to achieve
the maintenance dosage (2.2, 2.3).
• The maintenance dosage of WEGOVY® in adults is either 2.4
mg (recommended) or 1.7 mg once weekly (2.2).
• The maintenance dosage of WEGOVY® in pediatric patients
aged 12 years and older is 2.4 mg once weekly (2.3).
——— DOSAGE FORMS AND STRENGTHS ———Injection: pre-filled, single-dose pen that delivers doses of0.25 mg, 0.5 mg, 1 mg, 1.7 mg or 2.4 mg (3).
——— CONTRAINDICATIONS ———• Personal or family history of MTC or in patients with MEN2
(4).
• Known hypersensitivity to semaglutide or any of the excipientsin WEGOVY® (4).
——— WARNINGS AND PRECAUTIONS ———• Acute Pancreatitis: Has occurred in clinical trials. Discontinue
promptly if pancreatitis is suspected. Do not restart if
pancreatitis is confirmed (5.2).
• Acute Gallbladder Disease: Has occurred in clinical trials. Ifcholelithiasis is suspected, gallbladder studies and clinicalfollow-up are indicated (5.3).
• Hypoglycemia: Concomitant use with insulin or an insulin
secretagogue may increase the risk of hypoglycemia,
including severe hypoglycemia. Reducing the dose of insulin
or insulin secretagogue may be necessary. Inform all patientsof the risk of hypoglycemia and educate them on the signs andsymptoms of hypoglycemia (5.4).

6

7

8

10
11

5.8	Heart Rate Increase
5.9	Suicidal Behavior and Ideation
ADVERSE REACTIONS
6.1	Clinical Trials Experience
6.2 Postmarketing Experience
DRUG INTERACTIONS
7.1	Concomitant Use with Insulin or an Insulin
Secretagogue (e.g., Sulfonylurea)
7.2	Oral Medications
USE IN SPECIFIC POPULATIONS
8.1	Pregnancy
8.2	Lactation
8.3	Females and Males of Reproductive Potential
8.4	Pediatric Use
8.5	Geriatric Use
8.6	Renal Impairment
8.7	Hepatic Impairment
OVERDOSAGEDESCRIPTION

1• Acute Kidney Injury: Has occurred. Monitor renal function
when initiating or escalating doses of WEGOVY® in patients
reporting severe adverse gastrointestinal reactions orin those with renal impairment reporting severe adverse
gastrointestinal reactions (5.5).
• Hypersensitivity Reactions: Anaphylactic reactions andangioedema have been reported postmarketing. Discontinue
WEGOVY® if suspected and promptly seek medical advice(5.6).
• Diabetic Retinopathy Complications in Patients with Type
2 Diabetes: Has been reported in trials with semaglutide.
Patients with a history of diabetic retinopathy should bemonitored (5.7).
• Heart Rate Increase: Monitor heart rate at regular intervals(5.8).
• Suicidal Behavior and Ideation: Monitor for depression or
suicidal thoughts. Discontinue WEGOVY® if symptoms
develop (5.9).
——— ADVERSE REACTIONS ———Most common adverse reactions (incidence ≥ 5%) in adults
or pediatric patients aged 12 years and older are: nausea,
diarrhea, vomiting, constipation, abdominal pain, headache,fatigue, dyspepsia, dizziness, abdominal distension, eructation,
hypoglycemia in patients with type 2 diabetes, flatulence,
gastroenteritis, gastroesophageal reflux disease, andnasopharyngitis (6.1).
To report SUSPECTED ADVERSE REACTIONS, contact
Novo Nordisk Inc., at 1-833-934-6891 or FDA at 1-800FDA-1088 or www.fda.gov/medwatch.
——— DRUG INTERACTIONS ———WEGOVY® delays gastric emptying. May impact absorption of
concomitantly administered oral medications. Use with caution(7.2).
——— USE IN SPECIFIC POPULATIONS ———• Pregnancy: May cause fetal harm. When pregnancy isrecognized, discontinue WEGOVY® (8.1).
• Females and Males of Reproductive Potential: Discontinue
WEGOVY® at least 2 months before a planned pregnancy
because of the long half-life of semaglutide (8.3).
See 17 for PATIENT COUNSELING INFORMATION and
Medication Guide.
Revised: 03/2024

12

13

14

16
17

CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
12.6	Immunogenicity
NONCLINICAL TOXICOLOGY
13.1	Carcinogenesis, Mutagenesis, Impairment of
Fertility
CLINICAL STUDIES
14.1	Cardiovascular Outcomes Trial in Adult Patientswith Cardiovascular Disease and Either Obesity or
Overweight
14.2	Weight Reduction and Long-term MaintenanceStudies in Adults with Obesity or Overweight
14.3	Weight Reduction and Long-Term MaintenanceStudy in Pediatric Patients Aged 12 Years and Olderwith Obesity
HOW SUPPLIED/STORAGE AND HANDLINGPATIENT COUNSELING INFORMATION*Sections or subsections omitted from the full prescribing
information are not listed.

Wegovy ® (semaglutide) injection 2.4 mg
FULL PRESCRIBING INFORMATIONWARNING: RISK OF THYROID C−CELL TUMORS• In rodents, semaglutide causes dose-dependentand treatment-duration-dependent thyroid C-celltumors at clinically relevant exposures. It is
unknown whether WEGOVY® causes thyroid
C-cell tumors, including medullary thyroid
carcinoma (MTC), in humans as human relevanceof semaglutide-induced rodent thyroid C-celltumors has not been determined [see Warnings
and Precautions (5.1) and Nonclinical Toxicology(13.1)].
• WEGOVY® is contraindicated in patients with apersonal or family history of MTC or in patientswith Multiple Endocrine Neoplasia syndrome type2 (MEN 2) [see Contraindications (4)]. Counsel
patients regarding the potential risk for MTC withthe use of WEGOVY® and inform them of symptomsof 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 forearly detection of MTC in patients treated with
WEGOVY® [see Contraindications (4) and Warnings
and Precautions (5.1)].
1
INDICATIONS AND USAGEWEGOVY® is indicated in combination with a reduced calorie dietand increased physical activity:• to reduce the risk of major adverse cardiovascular events(cardiovascular death, non-fatal myocardial infarction, or
non-fatal stroke) in adults with established cardiovasculardisease and either obesity or overweight.
• to reduce excess body weight and maintain weight reduction
long term in:• Adults and pediatric patients aged 12 years and older withobesity• Adults with overweight in the presence of at least one
weight-related comorbid condition.
Limitations of Use• WEGOVY® contains semaglutide. Coadministration with othersemaglutide-containing products or with any other GLP-1
receptor agonist is not recommended.
2
DOSAGE AND ADMINISTRATION
2.1 Important Monitoring and Administration
Instructions• In patients with type 2 diabetes, monitor blood glucose prior
to starting WEGOVY® and during WEGOVY® treatment [seeWarnings and Precautions (5.4)].
• Prior to initiation of WEGOVY®, train patients on proper
injection technique. Refer to the accompanying Instructions
for Use for complete administration instructions with
illustrations.
• Inspect WEGOVY® visually prior to each injection. Only use if
solution is clear, colorless, and contains no particles.
• Administer WEGOVY® in combination with a reduced-calorie
diet and increased physical activity.
• Administer WEGOVY® once weekly, on the same day each
week, at any time of day, with or without meals.
• Inject WEGOVY® subcutaneously in the abdomen, thigh,or upper arm. The time of day and the injection site can bechanged without dose adjustment.
2.2 Recommended Dosage in Adults
Dosage Initiation and Escalation• Initiate WEGOVY® with a dosage of 0.25 mg injectedsubcutaneously once weekly. Then follow the dose escalation
schedule presented in Table 1 to minimize gastrointestinal
adverse reactions [see Adverse Reactions (6.1)].
• If patients do not tolerate a dose during dosage escalation,
consider delaying dosage escalation for 4 weeks.
Table 1. Recommended Dosage Regimen for Adults
Treatment
Initiation
Escalation
MaintenanceWeeks
1 through 4
5 through 8
9 through 12
13 through 16
17 and onward

Once weekly
Subcutaneous
Dosage0.25 mg
0.5 mg
1 mg
1.7 mg
1.7 mg or 2.4 mg

Maintenance Dosage• The maintenance dosage of WEGOVY® in adults is either
2.4 mg (recommended) or 1.7 mg once weekly. Consider
treatment response and tolerability when selecting themaintenance dosage [see Clinical Studies (14.2)].
2.3 Recommended Dosage in Pediatric Patients Aged
12 Years and Older
Dosage Initiation and Escalation• Initiate WEGOVY® according to the dosage escalation
schedule in Table 2 to minimize gastrointestinal adverse
reactions [see Adverse Reactions (6.1)].
• If patients do not tolerate a dose during dosage escalation,
consider delaying dosage escalation for 4 weeks.
• The 0.25 mg, 0.5 mg, and 1 mg once-weekly dosages are
initiation and escalation dosages and are not approved as
maintenance dosages.
Table 2. Recommended Dosage Regimen for PediatricPatients Aged 12 Years and Older
Treatment
Initiation
Escalation
MaintenanceWeeks
1 through 4
5 through 8
9 through 12
13 through 16
17 and onward

Once weekly
Subcutaneous
Dosage0.25 mga
0.5 mga
1 mga
1.7 mgb
2.4 mga

Not approved as maintenance dosagesb See Dosage Modifications for Adverse Reactions

Maintenance Dosage• The maintenance dosage of WEGOVY® in pediatric patients
aged 12 years and older is 2.4 mg once weekly.
Dosage Modifications for Adverse Reactions• If patients do not tolerate the 2.4 mg once-weekly maintenancedosage, the maintenance dosage may be reduced to 1.7 mg
once weekly.
• Discontinue WEGOVY® if the patient cannot tolerate the
1.7 mg once-weekly dosage.
2.4 Recommendations Regarding Missed Dose
• If one dose is missed and the next scheduled dose is morethan 2 days away (48 hours), administer WEGOVY® as soon as
possible. If one dose is missed and the next scheduled dose isless than 2 days away (48 hours), do not administer the dose.
Resume dosing on the regularly scheduled day of the week.
• If 2 or more consecutive doses are missed, resume dosing asscheduled or, if needed, reinitiate WEGOVY® and follow thedose escalation schedule, which may reduce the occurrenceof gastrointestinal symptoms associated with reinitiation oftreatment.
3
DOSAGE FORMS AND STRENGTHS
Injection: clear, colorless solution available in 5 pre-filled,
disposable, single-dose pens:• 0.25 mg/0.5 mL• 0.5 mg/0.5 mL• 1 mg/0.5 mL• 1.7 mg/0.75 mL• 2.4 mg/0.75 mL
4
CONTRAINDICATIONSWEGOVY® is contraindicated in the following conditions:• A personal or family history of MTC or in patients with MEN 2[see Warnings and Precautions (5.1)].
• A prior serious hypersensitivity reaction to semaglutide or toany of the excipients in WEGOVY®. Serious hypersensitivity
reactions, including anaphylaxis and angioedema, have beenreported with WEGOVY® [see Warnings and Precautions(5.6)].
5
WARNINGS AND PRECAUTIONS
5.1 Risk of Thyroid C-Cell Tumors
In mice and rats, semaglutide caused a dose-dependent andtreatment-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 WEGOVY® causes thyroid C-celltumors, including MTC, in humans, as human relevance ofsemaglutide-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;2
the data in these reports are insufficient to establish or exclude
a causal relationship between MTC and GLP-1 receptor agonist
use in humans.
WEGOVY® is contraindicated in patients with a personal orfamily history of MTC or in patients with MEN 2. Counsel patients
regarding the potential risk for MTC with the use of WEGOVY®
and inform them of symptoms of thyroid tumors (e.g. a mass inthe neck, dysphagia, dyspnea, persistent hoarseness).
Routine monitoring of serum calcitonin or using thyroid
ultrasound is of uncertain value for early detection of MTC inpatients treated with WEGOVY®. 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 calcitoninvalues greater than 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 orneck 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 treatedwith GLP-1 receptor agonists, including semaglutide. Acutepancreatitis was observed in patients treated with WEGOVY®
in clinical trials [see Adverse Reactions (6)]. After initiation of
WEGOVY®, observe patients carefully for signs and symptomsof acute pancreatitis (including persistent severe abdominal pain,
sometimes radiating to the back, and which may or may not be
accompanied by vomiting). If acute pancreatitis is suspected,
WEGOVY® should promptly be discontinued, and appropriate
management should be initiated. If acute pancreatitis isconfirmed, WEGOVY® should not be restarted.
There is limited experience from clinical trials with WEGOVY®
in patients with a history of pancreatitis. It is unknown if patientswith a history of pancreatitis are at higher risk for developmentof pancreatitis on WEGOVY®.
5.3 Acute Gallbladder Disease
Treatment with WEGOVY® is associated with an increased
occurrence of cholelithiasis and cholecystitis. The incidence ofcholelithiasis and cholecystitis was higher in WEGOVY® -treated
pediatric patients aged 12 years and older than in WEGOVY® treated adults. In randomized clinical trials in adult patients,
cholelithiasis was reported by 1.6% of WEGOVY® -treatedpatients and 0.7% of placebo-treated patients. Cholecystitis
was reported by 0.6% of WEGOVY® -treated adult patients and
0.2% of placebo-treated patients. In a clinical trial in pediatricpatients aged 12 years and older, cholelithiasis was reported by
3.8% of WEGOVY® -treated patients and 0% placebo-treatedpatients. Cholecystitis was reported by 0.8% of WEGOVY® treated pediatric patients and 0% placebo-treated patients [seeAdverse Reactions (6.1)].
Substantial or rapid weight loss can increase the risk ofcholelithiasis; however, the incidence of acute gallbladder disease
was greater in WEGOVY® -treated patients than in placebo-treatedpatients, even after accounting for the degree of weight loss. Ifcholelithiasis is suspected, gallbladder studies and appropriate
clinical follow-up are indicated.
5.4 Hypoglycemia
WEGOVY® lowers blood glucose and can cause hypoglycemia.
In a trial of adult patients with type 2 diabetes and body massindex (BMI) greater than or equal to 27 kg/m 2, hypoglycemia(defined as a plasma glucose less than 54 mg/dL) was reported
in 6.2% of WEGOVY® -treated patients versus 2.5% of placebotreated patients. One episode of severe hypoglycemia (requiring
the assistance of another person) was reported in one WEGOVY® treated patient versus no placebo-treated patients.
Patients with diabetes mellitus taking WEGOVY® in combination
with insulin or an insulin secretagogue (e.g., sulfonylurea) may
have an increased risk of hypoglycemia, including severe
hypoglycemia. Hypoglycemia has been observed in patientstreated with semaglutide at doses of 0.5 and 1 mg in combination
with insulin. The use of WEGOVY® (semaglutide 2.4 mg or 1.7
mg once weekly) in patients with type 1 diabetes mellitus or in
combination with insulin has not been evaluated.
Inform patients of the risk of hypoglycemia and educate themon the signs and symptoms of hypoglycemia. In patients withdiabetes, monitor blood glucose prior to starting WEGOVY®
and during WEGOVY® treatment. When initiating WEGOVY®,
consider reducing the dose of concomitantly administered insulin
or insulin secretagogue (such as sulfonylureas) to reduce the riskof hypoglycemia [see Drug Interactions (7)].
5.5 Acute Kidney Injury
There have been postmarketing reports of acute kidney injury
and worsening of chronic renal failure, which have in some cases
required hemodialysis, in patients treated with semaglutide.

Wegovy ® (semaglutide) injection 2.4 mg
Patients with renal impairment may be at greater risk of acutekidney injury, but some of these events have been reported inpatients without known underlying renal disease. A majority of
the reported events occurred in patients who had experienced
nausea, vomiting, or diarrhea, leading to volume depletion [seeAdverse Reactions (6)].
Monitor renal function when initiating or escalating doses of
WEGOVY® in patients reporting severe adverse gastrointestinal
reactions. Monitor renal function in patients with renal impairment
reporting any adverse reactions that could lead to volume depletion.
5.6 Hypersensitivity Reactions
Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema)
have been reported with WEGOVY®. If hypersensitivity reactions
occur, discontinue use of WEGOVY®, treat promptly per standardof care, and monitor until signs and symptoms resolve. WEGOVY®
is contraindicated in patients with a prior serious hypersensitivity
reaction to semaglutide or to any of the excipients in WEGOVY®
[see Adverse Reactions (6.2)].
Anaphylaxis and angioedema have been reported with other
GLP-1 receptor agonists. Use caution in a patient with a historyof anaphylaxis or angioedema with another GLP-1 receptor agonist
because it is unknown whether such patients will be predisposedto these reactions with WEGOVY®.
5.7 Diabetic Retinopathy Complications in Patientswith Type 2 Diabetes
In a trial of adult patients with type 2 diabetes and BMI greater thanor equal to 27 kg/m2, diabetic retinopathy was reported by 4.0%
of WEGOVY® -treated patients and 2.7% placebo-treated patients.
In a 2-year trial with semaglutide 0.5 mg and 1 mg once-weekly
injection in adult patients with type 2 diabetes and highcardiovascular risk, diabetic retinopathy complications (which was
a 4-component adjudicated endpoint) occurred in patients treatedwith semaglutide injection (3.0%) 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%) thanamong patients without a known history of diabetic retinopathy(semaglutide injection 0.7%, placebo 0.4%).
Rapid improvement in glucose control has been associatedwith a temporary worsening of diabetic retinopathy. The effectof long-term glycemic control with semaglutide on diabetic
retinopathy complications has not been studied. Patients with ahistory of diabetic retinopathy should be monitored for progressionof diabetic retinopathy.
5.8 Heart Rate Increase
Treatment with WEGOVY® was associated with increases in restingheart rate. Mean increases in resting heart rate of 1 to 4 beats per
minute (bpm) were observed in WEGOVY® -treated adult patientscompared to placebo in clinical trials. More adult patients treatedwith WEGOVY® compared with placebo had maximum changes
from baseline at any visit of 10 to 19 bpm (41% versus 34%,
respectively) and 20 bpm or more (26% versus 16%, respectively).
In a clinical trial in pediatric patients aged 12 years and older withnormal baseline heart rate, more patients treated with WEGOVY®
compared to placebo had maximum changes in heart rate of 20
bpm or more (54% versus 39%) [see Adverse Reactions (6.1)].
Monitor heart rate at regular intervals consistent with usual clinicalpractice. Instruct patients to inform their healthcare providers of
palpitations or feelings of a racing heartbeat while at rest during
WEGOVY® treatment. If patients experience a sustained increase
in resting heart rate, discontinue WEGOVY®.
5.9 Suicidal Behavior and Ideation
Suicidal behavior and ideation have been reported in clinical trials
with other weight management products. Monitor patients treatedwith WEGOVY® for the emergence or worsening of depression,suicidal thoughts or behavior, and/or any unusual changes in moodor behavior. Discontinue WEGOVY® in patients who experience
suicidal thoughts or behaviors. Avoid WEGOVY® in patients witha history of suicidal attempts or active suicidal ideation.
6
ADVERSE REACTIONS
The following serious adverse reactions are described below orelsewhere in the prescribing information:• Risk of Thyroid C-Cell Tumors [see Warnings and Precautions(5.1)]• Acute Pancreatitis [see Warnings and Precautions (5.2)]• Acute Gallbladder Disease [see Warnings and Precautions(5.3)]• Hypoglycemia [see Warnings and Precautions (5.4)]• Acute Kidney Injury [see Warnings and Precautions (5.5)]• Hypersensitivity Reactions [see Warnings and Precautions(5.6)]• Diabetic Retinopathy Complications in Patients with Type 2
Diabetes [see Warnings and Precautions (5.7)]• Heart Rate Increase [see Warnings and Precautions (5.8)]• Suicidal Behavior and Ideation [see Warnings and Precautions(5.9)]
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 studiesof another drug and may not reflect the rates observed in practice.
Adverse Reactions in Clinical Trials in Adults with
Obesity or Overweight
WEGOVY ® 2.4 mg Subcutaneous Weekly Dosage
WEGOVY® was evaluated for safety in 3 randomized, double-blind,placebo-controlled trials that included 2,116 adult patients withobesity or overweight treated with 2.4 mg WEGOVY® for up to
68 weeks and a 7 week off-drug follow-up period [see ClinicalStudies (14.2)]. Baseline characteristics included a mean ageof 48 years, 71% female, 72% White, 14% Asian, 9% Black or
African American, and 5% reported as other or unknown; and85% were not Hispanic or Latino ethnicity, 13% were Hispanic
or Latino ethnicity, and 2% reported as unknown. The baselinecharacteristics were 42% with hypertension, 19% with type 2
diabetes, 43% with dyslipidemia, 28% with a BMI greater than
40 kg/m2, and 4% with cardiovascular disease.
In these clinical trials, 6.8% of patients treated with 2.4 mg
WEGOVY® and 3.2% of patients treated with placebo permanently
discontinued treatment as a result of adverse reactions. The mostcommon adverse reactions leading to discontinuation were nausea(1.8% versus 0.2%), vomiting (1.2% versus 0%), and diarrhea(0.7% versus 0.1%) for WEGOVY® and placebo, respectively.
Adverse reactions reported in clinical trials in adults and greaterthan or equal to 2% of WEGOVY® -treated patients and more
frequently than in placebo-treated patients are shown in Table 3.
Table 3. A dverse Reactions (≥2% and Greater Than
Placebo) in WEGOVY® -treated Adults with
Obesity or Overweight
WEGOVY®
Placebo
2.4 mg
N=1,261 N=2,116%%
Nausea16
44
Diarrhea
16
30
Vomiting
624
Constipation
11
24
Abdominal Paina
10
20
Headache
10
14
Fatigueb
5
11
Dyspepsia
3
9
Dizziness48
Abdominal Distension
57Eructation<1
7
Hypoglycemia in T2DMc
2
6
Flatulence
4
6
Gastroenteritis
4
6
Gastroesophageal Reflux Disease
3
5
Gastritisd
1
4
Gastroenteritis Viral
3
4
Hair Loss
1
3
Dysesthesiae
12aIncludes abdominal pain, abdominal pain upper, abdominal pain lower,

gastrointestinal pain, abdominal tenderness, abdominal discomfort andepigastric discomfort

b Includes fatigue and astheniac D efined as blood glucose <54 mg/dL with or without symptoms ofhypoglycemia or severe hypoglycemia (requiring the assistance of anotherperson) in patients with type 2 diabetes not on concomitant insulin (Study 3,
WEGOVY® N=403, Placebo N=402). See text below for further information
regarding hypoglycemia in patients with and without type 2 diabetes. T2DM =type 2 diabetes mellitus
dIncludes chronic gastritis, gastritis, gastritis erosive, and reflux gastritis
eIncludes paresthesia, hyperesthesia, burning sensation, allodynia, dysesthesia,
skin burning sensation, pain of skin, and sensitive skinIn a cardiovascular outcomes trial, 8,803 patients were exposed to
WEGOVY® for a median of 37.3 months and 8,801 patients were
exposed to placebo for a median of 38.6 months [see ClinicalStudies (14.1)]. Safety data collection was limited to serious
adverse events (including death), adverse events leading todiscontinuation, and adverse events of special interest. Sixteen
percent (16%) of WEGOVY® -treated patients and 8% of placebotreated patients, respectively, discontinued study drug due to an
adverse event. Additional information from this trial is included
in subsequent sections below when relevant.

3
Adverse Reactions in a Clinical Trial of PediatricPatients Aged 12 Years and Older with Obesity
WEGOVY® was evaluated in a 68-week, double-blind, randomized,
parallel group, placebo-controlled, multi-center trial in 201
pediatric patients aged 12 years and older with obesity [see ClinicalStudies (14.3)]. Baseline characteristics included a mean age of
15.4 years; 38% of patients were male; 79% were White, 8% wereBlack or African American, 2% were Asian, and 11% were of otheror unknown race; and 11% were of Hispanic or Latino ethnicity.
The mean baseline body weight was 107.5 kg, and mean BMI
was 37 kg/m2.
Table 4 shows adverse reactions reported in greater than or equal
to 3% of WEGOVY® -treated pediatric patients and more frequently
than in the placebo group from a study in pediatric patients aged
12 years and older.
Table 4. A dverse Reactions (≥3% and Greater thanPlacebo) in WEGOVY® -Treated PediatricPatients Aged 12 Years and Older with Obesity
WEGOVY®
Placebo
2.4 mg
N=67
N=133
%
%
Nausea18
42
Vomiting
1036
Diarrhea
19
22
Headache16
17
Abdominal Pain
6
15
Nasopharyngitis
10
12
Dizziness
3
8
Gastroenteritis
37Constipation
2
6
Gastroesophageal Reflux Disease2
4Sinusitis
2
4
Urinary tract infection
2
4
Ligament sprain
2
4
Anxiety2
4
Hair Loss
04
Cholelithiasis
04Eructation
0
4
Influenza
0
3
Rash
0
3
Urticaria
0
3
Other Adverse Reactions in Adults and/or PediatricPatients
Acute Pancreatitis
In WEGOVY® clinical trials in adults, acute pancreatitis was
confirmed by adjudication in 4 WEGOVY® -treated patients (0.2
cases per 100 patient years) versus 1 in placebo-treated patients(less than 0.1 cases per 100 patient years). One additional caseof acute pancreatitis was confirmed in a patient treated with
WEGOVY® in another clinical trial.
Acute Gallbladder Disease
In WEGOVY® clinical trials in adults, cholelithiasis was reported by
1.6% of WEGOVY® -treated patients and 0.7% of placebo-treatedpatients. Cholecystitis was reported by 0.6% of WEGOVY® -treatedadult patients and 0.2% of placebo-treated patients. In a clinical
trial in pediatric patients aged 12 years and older [see ClinicalStudies (14.3)], cholelithiasis was reported by 3.8% of WEGOVY® treated patients and 0% placebo-treated patients. Cholecystitis
was reported by 0.8% of WEGOVY® -treated pediatric patientsand 0% placebo-treated patients.
Hypoglycemia
Patients with Type 2 Diabetes
In a trial of adult patients with type 2 diabetes and BMI greaterthan or equal to 27 kg/m 2, clinically significant hypoglycemia(defined as a plasma glucose less than 54 mg/dL) was reported
in 6.2% of WEGOVY® -treated patients versus 2.5% of placebotreated patients. A higher rate of clinically significant hypoglycemic
episodes was reported with WEGOVY® (semaglutide 2.4 mg) versus
semaglutide 1 mg (10.7 vs. 7.2 episodes per 100 patient years of
exposure, respectively); the rate in the placebo-treated group was
3.2 episodes per 100 patient years of exposure. In addition, one
episode of severe hypoglycemia requiring intravenous glucose wasreported in a WEGOVY® -treated patient versus none in placebotreated patients. The risk of hypoglycemia was increased when
WEGOVY® was used with a sulfonylurea.
Patients without Type 2 Diabetes
Episodes of hypoglycemia have been reported with GLP-1 receptor
agonists in adult patients without type 2 diabetes mellitus. In
WEGOVY® clinical trials in adult patients without type 2 diabetes

Wegovy ® (semaglutide) injection 2.4 mg
mellitus, there was no systematic capturing or reporting of
hypoglycemia.
In a cardiovascular outcomes trial in adult patients without type2 diabetes, 3 episodes of serious hypoglycemia were reported in
WEGOVY® -treated patients versus 1 episode in placebo. Patientswith a history of bariatric surgery (a risk factor for hypoglycemia)
had more events of serious hypoglycemia while taking WEGOVY®
(2.3%, 2/87) than placebo (0%, 0/97).
Acute Kidney Injury
Acute kidney injury occurred in clinical trials in 7 adult patients(0.4 cases per 100 patient years) receiving WEGOVY® versus 4
patients (0.2 cases per 100 patient years of exposure) receiving
placebo. Some of these adverse reactions occurred in association
with gastrointestinal adverse reactions or dehydration. In addition,
2 patients treated with WEGOVY® had acute kidney injury withdehydration in other clinical trials. The risk of renal adverse
reactions with WEGOVY® was increased in adult patients witha history of renal impairment (trials included 65 patients with ahistory of moderate or severe renal impairment at baseline), andoccurred more frequently during dose titration.
Retinal Disorders in Patients with Type 2 Diabetes
In a trial of adult patients with type 2 diabetes and BMI greaterthan or equal to 27 kg/m2, retinal disorders were reported by 6.9%of patients treated with WEGOVY® (semaglutide 2.4 mg), 6.2%
of patients treated with semaglutide 1 mg, and 4.2% of patientstreated with placebo. The majority of events were reported as
diabetic retinopathy (4.0%, 2.7%, and 2.7%, respectively) andnon-proliferative retinopathy (0.7%, 0%, and 0%, respectively).
Increase in Heart Rate
Mean increases in resting heart rate of 1 to 4 beats per minute (bpm)were observed with routine clinical monitoring in WEGOVY® treated adult patients compared to placebo in clinical trials. In trials
in which adult patients were randomized prior to dose-escalation,
more patients treated with WEGOVY®, compared with placebo, had
maximum changes from baseline at any visit of 10 to 19 bpm (41%versus 34%, respectively) and 20 bpm or more (26% versus 16%,
respectively). In a clinical trial in pediatric patients aged 12 years
and older with normal baseline heart rate, more patients treatedwith WEGOVY® compared to placebo had maximum changes inheart rate of 20 bpm or more (54% versus 39%).
Hypotension and Syncope
Adverse reactions related to hypotension (hypotension, orthostatic
hypotension, and decreased blood pressure) were reported in
1.3% of WEGOVY® -treated adult patients versus 0.4% of placebotreated patients and syncope was reported in 0.8% of WEGOVY® treated patients versus 0.2% of placebo-treated patients. Somereactions were related to gastrointestinal adverse reactionsand volume loss associated with WEGOVY®. Hypotension andorthostatic hypotension were more frequently seen in patients on
concomitant antihypertensive therapy. In a clinical trial in pediatricpatients aged 12 years and older, hypotension was reported in
2.3% of WEGOVY® -treated patients versus 0% in placebo-treatedpatients.
Appendicitis
Appendicitis (including perforated appendicitis) occurred in 10(0.5%) WEGOVY® -treated adult patients and 2 (0.2%) patients
receiving placebo.
Gastrointestinal Adverse Reactions
In clinical trials in adults, 73% of WEGOVY® -treated patientsand 47% of patients receiving placebo reported gastrointestinal
adverse reactions, including severe reactions that were reported
more frequently among patients receiving WEGOVY® (4.1%) thanplacebo (0.9%). The most frequently reported reactions were
nausea (44% vs. 16%), vomiting (25% vs. 6%), and diarrhea(30% vs. 16%). Other reactions that occurred at a higher incidence
among WEGOVY® -treated adult patients included dyspepsia,
abdominal pain, abdominal distension, eructation, flatulence,
gastroesophageal reflux disease, gastritis, hemorrhoids, andhiccups. These reactions increased during dose escalation.
In the pediatric clinical trial, 62% of WEGOVY® -treated patientsand 42% of placebo-treated patients reported gastrointestinal
disorders. The most frequently reported reactions were nausea(42% vs. 18%), vomiting (36% vs. 10%), and diarrhea (22% vs.
19%). Other gastrointestinal-related reactions that occurred at ahigher incidence than placebo among WEGOVY® -treated pediatricpatients included abdominal pain, constipation, eructation,
gastroesophageal reflux disease, dyspepsia, and flatulence.
Permanent discontinuation of treatment as a result of agastrointestinal adverse reaction occurred in 4.3% of WEGOVY® treated adult patients versus 0.7% of placebo-treated patients. Ina pediatric clinical trial, 2.3% of patients treated with WEGOVY®
versus 1.5% of patients who received placebo discontinued
treatment as a result of gastrointestinal adverse reactions.

Injection Site Reactions
In clinical trials in adults, 1.4% of WEGOVY® -treated patientsand 1.0% of patients receiving placebo experienced injection
site reactions (including injection site pruritus, erythema,
inflammation, induration, and irritation).
Hypersensitivity Reactions
Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema)
have been reported with WEGOVY®.
In a pediatric clinical trial, rash was reported in 3% of WEGOVY® treated patients and 0% of placebo-treated patients, and urticaria
was reported in 3% of WEGOVY® -treated patients and 0% of
placebo-treated patients. In adult clinical trials, allergic reactions
occurred in 16% (8/50) of WEGOVY® -treated patients with antisemaglutide antibodies and in 7% (114/1659) of WEGOVY® treated patients who did not develop anti-semaglutide antibodies[see Clinical Pharmacology (12.6)].
Fractures
In the cardiovascular outcomes trial in adults, more fractures of
the hip and pelvis were reported on WEGOVY® than on placeboin female patients: 1.0% (24/2448) vs. 0.2% (5/2424), and inpatients ages 75 years and older: 2.4% (17/703) vs. 0.6% (4/663),
respectively.
Urolithiasis
In a cardiovascular outcomes trial, 1.2% of WEGOVY® -treatedpatients and 0.8% of patients receiving placebo reported
urolithiasis, including serious reactions that were reported more
frequently among patients receiving WEGOVY® (0.6%) thanplacebo (0.4%).
Dysgeusia
In clinical trials in adults, 1.7% of WEGOVY® -treated patients and
0.5% of placebo-treated patients reported dysgeusia.
Laboratory Abnormalities
Amylase and Lipase
Adult and pediatric patients treated with WEGOVY® had a mean
increase from baseline in amylase of 15-16% and lipase of
39%. These changes were not observed in the placebo group.
The clinical significance of elevations in lipase or amylase with
WEGOVY® is unknown in the absence of other signs and symptoms
of pancreatitis.
Liver Enzymes
In a pediatric clinical trial, increases in alanine aminotransferase(ALT) greater than or equal to 5 times the upper limit of normal
were observed in 4 (3%) WEGOVY® -treated patients comparedwith 0% of placebo-treated patients. In some patients, increases
in ALT and AST were associated with other confounding factors(such as gallstones). In the cardiovascular outcomes trial in
adults, increases in total bilirubin greater than or equal to 3 times
the upper limit of normal were observed in 0.3% (30/8585) of
WEGOVY® -treated patients versus 0.2% (14/8579) of placebotreated patients.
6.2 Postmarketing Experience
The following adverse reactions have been reported during postapproval use of semaglutide, the active ingredient of WEGOVY®.
Because these reactions are reported voluntarily from a populationof uncertain size, it is not always possible to reliably estimate theirfrequency or establish a causal relationship to drug exposure.
Gastrointestinal Disorders: acute pancreatitis and necrotizing
pancreatitis, sometimes resulting in death; ileus
Hypersensitivity: anaphylaxis, angioedema, rash, urticaria
Renal and Urinary Disorders: acute kidney injury
7
7.1

DRUG INTERACTIONS
Concomitant Use with Insulin or an Insulin
Secretagogue (e.g., Sulfonylurea)
WEGOVY® lowers blood glucose and can cause hypoglycemia.
The risk of hypoglycemia is increased when WEGOVY® is usedin combination with insulin or insulin secretagogues (e.g.,
sulfonylureas). The addition of WEGOVY® in patients treated withinsulin has not been evaluated.
When initiating WEGOVY®, consider reducing the dose ofconcomitantly administered insulin secretagogue (such as
sulfonylureas) or insulin to reduce the risk of hypoglycemia [seeWarnings and Precautions (5.4) and Adverse Reactions (6.1)].
7.2 Oral Medications
WEGOVY® causes a delay of gastric emptying and thereby
has the potential to impact the absorption of concomitantly
administered oral medications. In clinical pharmacology trials
with semaglutide 1 mg, semaglutide did not affect the absorptionof orally administered medications [see Clinical Pharmacology(12.3)]. Nonetheless, monitor the effects of oral medications
concomitantly administered with WEGOVY®.

48
USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Exposure Registry
There will be a pregnancy exposure registry that monitors
pregnancy outcomes in women exposed to semaglutide during
pregnancy. Pregnant women exposed to WEGOVY® and healthcare
providers are encouraged to contact Novo Nordisk at 1-877-3902760 or www.wegovypregnancyregistry.com.
Risk Summary
Based on animal reproduction studies, there may be potential
risks to the fetus from exposure to semaglutide during pregnancy.
Additionally, weight loss offers no benefit to a pregnant patient andmay cause fetal harm. When a pregnancy is recognized, advise thepregnant patient of the risk to a fetus, and discontinue WEGOVY®
(see Clinical Considerations). Available pharmacovigilance data
and data from clinical trials with WEGOVY® use in pregnant
patients are insufficient to establish a drug-associated risk of majorbirth defects, miscarriage or adverse maternal or fetal outcomes.
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 structuralabnormalities were observed at below the MRHD (rabbit) andgreater than or equal to 2-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 andmiscarriage for the indicated population are unknown. In the U.S.
general population, the estimated background risk of major birthdefects and miscarriage in clinically recognized pregnancies is2-4% and 15-20%, respectively.
Clinical Considerations
Disease-associated maternal and/or embryo/fetal risk
Appropriate weight gain based on pre-pregnancy weight iscurrently recommended for all pregnant patients, including those
who already have overweight or obesity, because of the obligatory
weight gain that occurs in maternal tissues during pregnancy.
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 (0.04-,
0.1-, and 0.4-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 inbody weight gain and food consumption were observed at all doselevels. 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(0.01-, 0.1-, and 0.9-fold the MRHD) were administered throughout
organogenesis from Gestation Day 6 to 19. Pharmacologicallymediated reductions in maternal body weight gain and foodconsumption 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
greater than or equal to 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 (0.4-, 2-, and 6-fold the MRHD) were administeredthroughout organogenesis, from Gestation Day 16 to 50.
Pharmacologically mediated, marked initial maternal body weightloss and reductions in body weight gain and food consumption
coincided with the occurrence of sporadic abnormalities (vertebra,
sternebra, ribs) at greater than or equal to 0.075 mg/kg twice
weekly (greater than or equal to 2 times 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 (0.2-, 1-, and 3-fold the MRHD) were administeredfrom Gestation Day 16 to 140. Pharmacologically mediated marked
initial maternal body weight loss and reductions in body weightgain and food consumption coincided with an increase in earlypregnancy losses and led to delivery of slightly smaller offspringat greater than or equal to 0.075 mg/kg twice weekly (greater thanor equal to 1-time human exposure).
8.2 Lactation
Risk Summary
There are no data on the presence of semaglutide or its metabolites
in human milk, the effects on the breastfed infant, or the effects on
milk production. Semaglutide was present in the milk of lactating

Wegovy ® (semaglutide) injection 2.4 mg
rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk(see Data). The developmental and health benefits of breastfeeding should be considered along withthe mother’s clinical need for WEGOVY® and any potential adverse effects on the breastfed infantfrom WEGOVY® or from the underlying maternal condition.
Data
In lactating rats, semaglutide was detected in milk at levels 3 to 12-fold lower than in maternal plasma.
8.3 Females and Males of Reproductive Potential
Because of the potential for fetal harm, discontinue WEGOVY® in patients at least 2 months before
they plan to become pregnant to account for the long half-life of semaglutide [see Use in Specific
Populations (8.1)].
8.4 Pediatric Use
The safety and effectiveness of WEGOVY® as an adjunct to a reduced calorie diet and increased
physical activity for weight reduction and long-term maintenance have been established in pediatricpatients aged 12 years and older with obesity. Use of WEGOVY® for this indication is supported bya 68-week, double-blind, placebo-controlled clinical trial in 201 pediatric patients aged 12 years
and older with a BMI corresponding to ≥95th percentile for age and sex and from studies in adultpatients with obesity [see Clinical Studies (14.3)].
Adverse reactions with WEGOVY® treatment in pediatric patients aged 12 years and older weregenerally similar to those reported in adults. Pediatric patients aged 12 years and older treated with
WEGOVY® had greater incidences of cholelithiasis, cholecystitis, hypotension, rash, and urticaria
compared to adults treated with WEGOVY® [see Adverse Reactions (6.1)].
There are insufficient data in pediatric patients with type 2 diabetes treated with WEGOVY® forobesity to determine if there is an increased risk of hypoglycemia with WEGOVY® treatment similar
to that reported in adults. Inform patients of the risk of hypoglycemia and educate them on the signs
and symptoms of hypoglycemia. In pediatric patients aged 12 years and older with type 2 diabetes,monitor blood glucose prior to starting WEGOVY® and during WEGOVY® treatment. When initiating
WEGOVY® in pediatric patients aged 12 years and older with type 2 diabetes, consider reducing
the dose of concomitantly administered insulin secretagogue (such as sulfonylureas) or insulin to
reduce the risk of hypoglycemia [see Warnings and Precautions (5.4)].
The safety and effectiveness of WEGOVY® have not been established in pediatric patients less than
12 years of age.
8.5 Geriatric Use
In the WEGOVY® clinical trials for weight reduction and long-term maintenance, 233 (9%) WEGOVY® treated patients were aged 65 to 75 years and 23 (1%) WEGOVY® -treated patients were aged 75 years
and older [see Clinical Studies (14.2)]. In a cardiovascular outcomes trial, 2656 (30%) WEGOVY® treated patients were aged 65 to 75 years and 703 (8%) WEGOVY® -treated patients were aged 75 years
and older [see Clinical Studies (14.1)]. No overall difference in effectiveness was observed between
patients aged 65 years and older and younger adult patients. In the cardiovascular outcomes trial,
patients aged 75 years and older reported more fractures of the hip and pelvis on WEGOVY® than onplacebo. Patients aged 75 years and older (WEGOVY® -treated and placebo-treated) reported more
serious adverse reactions overall compared to younger adult patients [see Adverse Reactions (6.1)].
8.6 Renal Impairment
No dose adjustment of WEGOVY® is recommended for patients with renal impairment. In a study inpatients with renal impairment, including end-stage renal disease, no clinically relevant change insemaglutide pharmacokinetics was observed [see Clinical Pharmacology (12.3)].
8.7 Hepatic Impairment
No dose adjustment of WEGOVY® is recommended for patients with hepatic impairment. In a study
in patients with different degrees of hepatic impairment, no clinically relevant change in semaglutide
pharmacokinetics was observed [see Clinical Pharmacology (12.3)].
10 OVERDOSAGE
Overdoses have been reported with other GLP-1 receptor agonists. Effects have included severe
nausea, severe vomiting, and severe hypoglycemia. In the event of overdose, appropriate supportive
treatment should be initiated according to the patient’s clinical signs and symptoms. In the eventof an overdose of WEGOVY®, consider contacting the Poison Help line (1-800-222-1222) or a
medical toxicologist for additional overdosage management recommendations. A prolonged periodof observation and treatment for these symptoms may be necessary, taking into account the long
half-life of WEGOVY® of approximately 1 week.
11 DESCRIPTIONWEGOVY® (semaglutide) injection, for subcutaneous use, contains semaglutide, a human GLP-1
receptor agonist (or GLP-1 analog). 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 inposition 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 C187H291N45O59 and the molecular weight is 4113.58 g/mol.
Figure 1. Structural Formula of semaglutide
O

7
H H

H
N

H3C

10
E

G

20
T

F

T

S

D

V

S

S

Y

L

E

G

Q

A

A

O

H
N

30
E

F

I

A

37
W

L

V

R

G

R

G OH

Lys26

CH3

O

O

N
H

O

NH
O
O

O

NH
OH

mg; sodium chloride, 8.25 mg; and water for injection. WEGOVY® has a pH of approximately 7.4.
Hydrochloric acid or sodium hydroxide may be added to adjust pH.

12 CLINICAL PHARMACOLOGY
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 regulator of appetite and caloric intake, and the GLP-1 receptor is present
in several areas of the brain involved in appetite regulation. Animal studies show that semaglutide
distributed to and activated neurons in brain regions involved in regulation of food intake.
The exact mechanism of cardiovascular risk reduction has not been established.
12.2 Pharmacodynamics
Semaglutide lowers body weight with greater fat mass loss than lean mass loss. Semaglutide
decreases calorie intake. The effects are likely mediated by affecting appetite.
Semaglutide stimulates insulin secretion and reduces glucagon secretion in a glucose-dependent
manner. These effects can lead to a reduction of blood glucose.
Gastric Emptying
Semaglutide delays gastric emptying.
Cardiac Electrophysiology (QTc)
The effect of semaglutide on cardiac repolarization was tested in a thorough QTc trial. Semaglutide
did not prolong QTc intervals at doses up to 1.5 mg at steady state.
12.3 Pharmacokinetics
Absorption
Absolute bioavailability of semaglutide is 89%. Maximum concentration of semaglutide is reached
1 to 3 days post dose.
Similar exposure was achieved with subcutaneous administration of semaglutide in the abdomen,thigh, or upper arm.
The average semaglutide steady state concentration following subcutaneous administration of
WEGOVY® was approximately 75 nmol/L in patients with either obesity (BMI greater than or equal
to 30 kg/m2) or overweight (BMI greater than or equal to 27 kg/m2). The steady state exposure of
WEGOVY® increased proportionally with doses up to 2.4 mg once weekly.
Distribution
The mean volume of distribution of semaglutide following subcutaneous administration in patients withobesity or overweight is approximately 12.5 L. Semaglutide is extensively bound to plasma albumin(greater than 99%) which results in decreased renal clearance and protection from degradation.
Elimination
The apparent clearance of semaglutide in patients with obesity or overweight is approximately
0.05 L/h. With an elimination half-life of approximately 1 week, semaglutide will be present in thecirculation for about 5 to 7 weeks after the last dose of 2.4 mg.
Metabolism
The primary route of elimination for semaglutide is metabolism following proteolytic cleavage of thepeptide backbone and sequential beta-oxidation of the fatty acid sidechain.
Excretion
The primary excretion routes of semaglutide-related material are via the urine and feces. Approximately
3% of the dose is excreted in the urine as intact semaglutide.
Specific Populations
The effects of intrinsic factors on the pharmacokinetics of semaglutide are shown in Figure 2.
Figure 2. Impact of intrinsic factors on semaglutide exposure
Intrinsic factor
Sex
Age group

Relative exposure (Cavg)
Ratio and 90% CI
Male
65–<75 years>=75 years

RaceBlack or African American
Asian
American Indian or Alaska Native
Hispanic or Latino
Ethnicity
Body weight
74 kg
143 kgMild
Renal function
Moderate
Injection site

ThighUpper arm
0.50

O
H
N

O

5

1 mL of WEGOVY® contains the following inactive ingredients: disodium phosphate dihydrate, 1.42

OH
O
O

WEGOVY® is a sterile, aqueous, clear, colorless solution. Each 0.5 mL single-dose pen contains
a solution of WEGOVY® containing 0.25 mg, 0.5 mg or 1 mg of semaglutide; and each 0.75 mL
single-dose pen contains a solution of WEGOVY® containing 1.7 or 2.4 mg of semaglutide. Each

1.0

2.0

Data are steady-state dose-normalized average semaglutide exposures relative to a reference subject profile (non-Hispanic
or Latino ethnicity, white female aged 18 to less than 65 years, with a body weight of 110 kg and normal renal function, who
injected in the abdomen). Body weight categories (74 and 143 kg) represent the 5% and 95% percentiles in the dataset.

Patients with Renal Impairment
Renal impairment did not impact the exposure of semaglutide in a clinically relevant manner. The
pharmacokinetics of semaglutide were evaluated following a single dose of 0.5 mg semaglutide ina study of patients with different degrees of renal impairment (mild, moderate, severe, or ESRD)
compared with subjects with normal renal function. The pharmacokinetics were also assessed insubjects with overweight (BMI 27-29.9 kg/m2) or obesity (BMI greater than or equal to 30 kg/m2)
and mild to moderate renal impairment, based on data from clinical trials.

Wegovy ® (semaglutide) injection 2.4 mg
Patients with Hepatic Impairment
Hepatic impairment did not impact the exposure of semaglutide. The pharmacokinetics of semaglutide
were evaluated following a single dose of 0.5 mg semaglutide in a study of patients with different
degrees of hepatic impairment (mild, moderate, severe) compared with subjects with normal hepaticfunction.
Drug Interactions Studies
In vitro studies have shown very low potential for semaglutide to inhibit or induce CYP enzymes,
or to inhibit drug transporters.
The delay of gastric emptying with semaglutide may influence the absorption of concomitantly
administered oral medications [see Drug Interactions (7.2)]. The potential effect of semaglutide
on the absorption of co-administered oral medications was studied in trials at semaglutide 1 mg
steady-state exposure. No clinically relevant drug-drug interactions with semaglutide (Figure 3)
were observed based on the evaluated medications. In a separate study, no apparent effect on therate of gastric emptying was observed with semaglutide 2.4 mg.
Figure 3. I mpact of semaglutide 1 mg on the pharmacokinetics of co-administered
medications
Co-administered
medication
S-warfarin
R-warfarin
Digoxin
Atorvastatin
Ethinylestradiol
Levonorgestrel

AUC0-12h
Cmax
AUC0-168h
Cmax
AUC0-168h
Cmax
AUC0-120h
Cmax
AUC0-72h
Cmax
AUC0-24h
Cmax
AUC0-24h
Cmax

cardiovascular disease (prior myocardial infarction, prior stroke, or peripheral arterial disease).
Patients with a history of type 1 or type 2 diabetes were excluded. Concomitant CV therapies could
be adjusted, at the discretion of the investigator, to ensure participants were treated according to thecurrent standard of care for patients with established cardiovascular disease.
In this trial, 17,604 patients were randomized to WEGOVY® or placebo. At baseline, the mean age
was 62 years (range 45-93), 72% were male, 84% were White, 4% were Black or African American,
and 8% were Asian, and 10% were Hispanic or Latino. Mean baseline body weight was 97 kg andmean BMI was 33 kg/m2. At baseline, prior myocardial infarction was reported in 76% of randomized
individuals, prior stroke in 23%, and peripheral arterial disease in 9%. Heart failure was reported
in 24% of patients. At baseline, cardiovascular disease and risk factors were managed with lipidlowering therapy (90%), platelet aggregation inhibitors (86%), angiotensin converting enzyme
inhibitors or angiotensin II receptor blockers (74%), and beta blockers (70%). A total of 10% had
moderate renal impairment (eGFR 30 to <60 mL/min/1.73m2) and 0.4% had severe renal impairment
eGFR <30 mL/min/1.73m2.
Results
In total, 96.9% of patients completed the trial, and vital status was available for 99.4% of patients.
The median follow-up duration was 41.8 months. A total of 31% of WEGOVY® -treated patients and
27% of placebo-treated patients permanently discontinued study drug.
For the primary analysis, a Cox proportional hazards model was used to test for superiority. Type 1
error was controlled across multiple tests.
WEGOVY® significantly reduced the risk for first occurrence of MACE. The estimated hazard ratio(95% CI) was 0.80 (0.72, 0.90) (see Figure 4 and Table 5).
Figure 4. C umulative Incidence Function: Time to First Occurrence of MACE in
Study 1
10

0.5

1

2

Relative exposure in terms of AUC and Cmax for each medication when given with semaglutide compared to without
semaglutide. Metformin and oral contraceptive drug (ethinylestradiol/levonorgestrel) were assessed at steady state.
Warfarin (S-warfarin/R-warfarin), digoxin and atorvastatin were assessed after a single dose.
Abbreviations: AUC: area under the curve, Cmax: maximum concentration, CI: confidence interval.

12.6 Immunogenicity
The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificityof the assay. Differences in assay methods preclude meaningful comparisons of the incidence ofanti-drug antibodies in the studies described below with the incidence of anti-drug antibodies inother studies, including those of semaglutide or of other semaglutide products.
During the 68-week treatment periods in Studies 2 and 3 [see Clinical Studies (14.2)], 50/1709 (3%)
of WEGOVY® -treated patients developed anti-semaglutide antibodies. Of these 50 WEGOVY® -treatedpatients, 28 patients (2% of the total WEGOVY® -treated study population) developed antibodies
that cross-reacted with native GLP-1. No identified clinically significant effect of anti-semaglutide
antibodies on pharmacokinetics for WEGOVY® was observed. There is insufficient evidence tocharacterize the effects of anti-semaglutide antibodies on pharmacodynamics or effectiveness ofsemaglutide.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
In a 2-year carcinogenicity study in CD-1 mice, subcutaneous doses of 0.3, 1 and 3 mg/kg/day (2-,8-, and 22-fold the maximum recommended human dose [MRHD] of 2.4 mg/week, based on AUC)
were administered to the males, and 0.1, 0.3 and 1 mg/kg/day (0.6-, 2-, and 5-fold MRHD) wereadministered to the females. A statistically significant increase in thyroid C-cell adenomas and anumerical increase in C-cell carcinomas were observed in males and females at all dose levels(greater than or equal to 0.6 times human exposure).
In a 2-year carcinogenicity study in Sprague Dawley rats, subcutaneous doses of 0.0025, 0.01, 0.025
and 0.1 mg/kg/day were administered (below quantification, 0.2-, 0.4-, and 2-fold the exposure at
the MRHD). A statistically significant increase in thyroid C-cell adenomas was observed in males
and females at all dose levels, and a statistically significant increase in thyroid C-cell carcinomas
was observed in males at greater than or equal to 0.01 mg/kg/day, at clinically relevant exposures.
Human relevance of thyroid C-cell tumors in rats is unknown and could not be determined by clinicalstudies or nonclinical studies [see Boxed Warning and Warnings and Precautions (5.1)]. Semaglutide
was not mutagenic or clastogenic in a standard battery of genotoxicity tests (bacterial mutagenicity[Ames] human lymphocyte chromosome aberration, rat bone marrow micronucleus).
In a combined fertility and embryo-fetal development study in rats, subcutaneous doses of 0.01,
0.03 and 0.09 mg/kg/day (0.04-, 0.1-, and 0.4-fold the MRHD) were administered to male and female
rats. Males were dosed for 4 weeks prior to mating, and females were dosed for 2 weeks prior tomating and throughout organogenesis until Gestation Day 17. No effects were observed on malefertility. In females, an increase in estrus cycle length was observed at all dose levels, together witha small reduction in numbers of corpora lutea at greater than or equal to 0.03 mg/kg/day. These
effects were likely an adaptive response secondary to the pharmacological effect of semaglutide on
food consumption and body weight.
14 CLINICAL STUDIES
14.1 Cardiovascular Outcomes Trial in Adult Patients with Cardiovascular Disease
and Either Obesity or Overweight
Overview of Clinical Trial
Study 1 (NCT03574597) was a multi-national, multi-center, placebo-controlled, double-blind trial
to determine the effect of WEGOVY® relative to placebo on major adverse cardiovascular events(MACE) when added to current standard of care, which included management of CV risk factors
and individualized healthy lifestyle counseling (including diet and physical activity). The primary
endpoint, MACE, was the time to first occurrence of a three-part composite outcome which included
cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke.

Patients with Event (%)

Metformin

Relative exposure
Ratio and 90% CI

6All patients were 45 years or older, with an initial BMI of 27 kg/m 2 or greater and established

Placebo

8
6

WEGOVY®

4

HR: 0.80
95% CI[0.72 - 0.90]

200Patients at risk
WEGOVY® 8803
Placebo
8801

6

12

18

24

30

36

42

48

54

4126
4015

1734
1672

71
59

Time from randomization (months)
8695
8652

8561
8487

8427
8326

8254
8164

7229
7101

5777
5660

Data from the in-trial period. Cumulative incidence estimates are based on time from randomization to first EAC-confirmed
cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke with non-CV death modeled as competingrisk using the Aalen-Johansen estimator. Patients without events of interest were censored at the end of their in-trial
observation period. Time from randomization to first cardiovascular death, non-fatal myocardial infarction, or non-fatal
stroke was analyzed using a Cox proportional hazards model with treatment as categorical fixed factor. The hazard ratio andconfidence interval are adjusted for the group sequential design using the likelihood ratio ordering.
HR: Hazard ratio; CI: confidence interval; CV: cardiovascular

The treatment effect for the primary composite endpoint, its components, and other relevant endpoints
in Study 1 are shown in Table 5.
Table 5. Treatment Effect for MACE and Other Events in Study 1
Patients with eventsn (%)
Placebo WEGOVY®
N=8,801
N=8,803
Primary composite endpoint
Composite of cardiovascular death, non-fatal
701 (8.0%) 569 (6.5%)
myocardial infarction, or non-fatal stroke1
Key secondary endpoints
Cardiovascular death3
262 (3.0%) 223 (2.5%)
All-cause death4458 (5.2%) 375 (4.3%)
Other secondary endpoints
Fatal or non-fatal myocardial infarction5334 (3.8%) 243 (2.8%)
Fatal or non-fatal stroke 5
178 (2.0%) 160 (1.8%)

Hazard Ratio(95% CI)
0.80 (0.72; 0.90)*2
0.85 (0.71; 1.01)
0.81 (0.71; 0.93)
0.72 (0.61; 0.85)
0.89 (0.72; 1.11)*p-value < 0.001, one-sided p-value
1Primary endpoint
2 Adjusted for group sequential design using the likelihood ratio ordering.
3Cardiovascular death was the first confirmatory secondary endpoint in the testing hierarchy and superiority was notconfirmed.
4 Confirmatory secondary endpoint. Not statistically significant based on the prespecified testing hierarchy.
5Not included in the prespecified testing hierarchy for controlling type-I error.
NOTE: Time to first event was analyzed in a Cox proportional hazards model with treatment as factor. For patients withmultiple events, only the first event contributed to the composite endpoint.

Wegovy ® (semaglutide) injection 2.4 mg
Table 6. Mean Changes in Anthropometry and Cardiometabolic Parameters at Week
104 in Study 11,2
PLACEBOWEGOVY®
Change from
Change from Difference fromBaseline
Baseline
PlaceboBaseline(LSMean)Baseline(LSMean)(LSMean)Body Weight (kg)96.8
-0.9 3
96.5-9.4 3-8.5 3
Waist Circumference (cm)
111.4
-1.0
111.3
-7.6
-6.5
Systolic Blood Pressure
131
-0.5
131
-3.8
-3.3
(mmHg)
Diastolic Blood Pressure
79
-0.5
79
-1.0
-0.5
(mmHg)
Heart Rate
69
0.7
69
3.8
3.1
HbA1c (%)
5.8
0.0
5.8
-0.3
-0.3
% Change% Change
Relativefrom
fromdifference fromBaseline
Baselineplacebo (%)
Baseline(LSMean)Baseline(LSMean)(LSMean)Total Cholesterol (mg/dL)4
156.0
-1.9
155.5
-4.6
-2.8
LDL Cholesterol (mg/dL)4
78.5
-3.1
78.5
-5.3
-2.2
HDL Cholesterol (mg/dL)4
44.2
0.6
44.1
4.9
4.2
Triglycerides (mg/dL)4
139.5
-3.2
138.6
-18.3
-15.6

Hispanic or Latino ethnicity. Mean body weight at randomization (week 20) was 96.1 kg and mean
BMI at randomization (week 20) was 34.4 kg/m2.
Study 6 was a 68-week trial that enrolled 401 East-Asian patients (Japan and South Korea) with BMI
greater than or equal to 35 kg/m2 and at least one weight-related comorbid condition or with BMI
27-34.9 kg/m2 and at least two weight-related comorbid conditions. The patients were randomized
2:1:1 to receive WEGOVY® 2.4 mg, WEGOVY® 1.7 mg, or placebo. At baseline, the mean age was
51 years, 63% were male, and all patients were Asian. Mean baseline body weight was 87.5 kg andmean BMI was 31.9 kg/m2. At baseline, 24.7% of patients had type 2 diabetes mellitus.
Results
The proportions of patients who discontinued study drug in Studies 2, 3, and 4 was 16.0% for the
WEGOVY® -treated group and 19.1% for the placebo-treated group, and 6.8% of patients treatedwith WEGOVY® and 3.2% of patients treated with placebo discontinued treatment due to an adverse
reaction [see Adverse Reactions (6.1)]. In Study 5, the proportions of patients who discontinued study
drug were 5.8% and 11.6% for WEGOVY® and placebo, respectively. In Study 6, the proportions ofpatients who discontinued study drug were 7.9%, 6.5%, and 3.0% for WEGOVY® 1.7 mg, WEGOVY®
2.4 mg, and placebo, respectively.
For Studies 2, 3 and 4, the primary efficacy parameters were mean percent change in body weight andthe percentages of patients achieving greater than or equal to 5% weight loss from baseline to week 68.
After 68 weeks, treatment with WEGOVY® resulted in a statistically significant reduction in bodyweight compared with placebo. Greater proportions of patients treated with WEGOVY® achieved 5%,
10% and 15% weight loss than those treated with placebo as shown in Table 7.
Table 7. Changes in Body Weight at Week 68 in Studies 2, 3, and 4

1Parameters listed in the table were not included in the pre-specified hierarchical testing.

2Responses were analysed using an ANCOVA with treatment as fixed factor and baseline value as covariate. Before analysis,

missing data were multiple imputed. The imputation model (linear regression) was done separately for each treatment arm
and included baseline value as a covariate and was fitted to all subjects with a measurement regardless of treatment status
at week 104.
3For body weight the ‘change from baseline’ and ‘difference to placebo’ the unit is percentage change from baseline.
4 Baseline value is the geometric mean.

The reduction of MACE with WEGOVY® was not impacted by age, sex, race, ethnicity, BMI at baseline,or level of renal function impairment.
14.2 Weight Reduction and Long-term Maintenance Studies in Adults with Obesity
or Overweight
Overview of Clinical Studies in Adults
The safety and efficacy of WEGOVY® for weight reduction and long-term maintenance of body weightin conjunction with a reduced calorie diet and increased physical activity were studied in three
68-week, randomized, double-blind, placebo-controlled trials; one 68-week, randomized, doubleblind, placebo withdrawal trial; and one 68-week, randomized, double-blind trial that investigated 2
different doses of WEGOVY® versus placebo. In Studies 2 (NCT#03548935), 3 (NCT#03552757), and4 (NCT#03611582), WEGOVY® or matching placebo was escalated to 2.4 mg subcutaneous weekly
during a 16-week period followed by 52 weeks on maintenance dose. In Study 5 (NCT#03548987),
WEGOVY® was escalated during a 20-week run-in period, and patients who reached a WEGOVY®
2.4 mg subcutaneous weekly dosage after the run-in period were randomized to either continued
treatment with WEGOVY® or placebo for 48 weeks. In Study 6 (NCT#03811574), WEGOVY® wasescalated to 1.7 mg or 2.4 mg subcutaneous weekly dosages or placebo over 12 to 16 weeks followedby 52 weeks on either maintenance dose.
In Studies 2, 3 and 5, all patients received instruction for a reduced calorie diet (approximately 500
kcal/day deficit) and increased physical activity counseling (recommended to a minimum of 150
min/week) that began with the first dose of study medication or placebo and continued throughout
the trial. In Study 4, patients received an initial 8-week low-calorie diet (total energy intake 1,000 to
1,200 kcal/day) followed by 60 weeks of a reduced calorie diet(1200-1800 kcal/day) and increased
physical activity (100 mins/week with gradual increase to 200 mins/week).
Study 2 was a 68-week trial that enrolled 1,961 patients with obesity (BMI greater than or equal to 30
kg/m2) or with overweight (BMI 27-29.9 kg/m2) and at least one weight-related comorbid condition,such as treated or untreated dyslipidemia or hypertension; patients with type 2 diabetes mellitus
were excluded. Patients were randomized in a 2:1 ratio to either WEGOVY® or placebo. At baseline,
mean age was 46 years (range 18-86), 74% were female, 75% were White, 13% were Asian and 6%
were Black or African American. A total of 12% were Hispanic or Latino ethnicity. Mean baseline
body weight was 105.3 kg and mean BMI was 37.9 kg/m2.
Study 3 was a 68-week trial that enrolled 807 patients with type 2 diabetes and BMI greater than orequal to 27 kg/m2. Patients included in the trial had HbA1c 7-10% and were treated with either: diet andexercise alone or 1 to 3 oral anti-diabetic drugs (metformin, sulfonylurea, glitazone or sodium-glucose
co-transporter 2 inhibitor). Patients were randomized in a 1:1 ratio to receive either WEGOVY® orplacebo. At baseline, the mean age was 55 years (range 19-84), 51% were female, 62% were White,
26% were Asian and 8% were Black or African American. A total of 13% were Hispanic or Latino
ethnicity. Mean baseline body weight was 99.8 kg and mean BMI was 35.7 kg/m2.
Study 4 was a 68-week trial that enrolled 611 patients with obesity (BMI greater than or equal to 30
kg/m2) or with overweight (BMI 27-29.9 kg/m2) and at least one weight-related comorbid condition
such as treated or untreated dyslipidemia or hypertension; patients with type 2 diabetes mellitus
were excluded. The patients were randomized in a 2:1 ratio to receive either WEGOVY® or placebo. At
baseline, the mean age was 46 years, 81% were female, 76% were White, 19% were Black or African
American and 2% were Asian. A total of 20% were Hispanic or Latino ethnicity. Mean baseline bodyweight was 105.8 kg and mean BMI was 38.0 kg/m2.
Study 5 was a 68-week trial that enrolled 902 patients with obesity (BMI greater than or equal to 30
kg/m2) or with overweight (BMI 27-29.9 kg/m2) and at least one weight-related comorbid condition
such as treated or untreated dyslipidemia or hypertension; patients with type 2 diabetes mellitus
were excluded. Mean body weight at baseline for the 902 patients was 106.8 kg and mean BMI was
38.3 kg/m². All patients received WEGOVY® during the run-in period of 20 weeks that included 16
weeks of dose escalation. Trial product was permanently discontinued before randomization in 99
of 902 patients (11%); the most common reason was adverse reactions (n=48, 5.3%); 803 patientsreached WEGOVY® 2.4 mg and were then randomized in a 2:1 ratio to either continue on WEGOVY®
or receive placebo. Among the 803 randomized patients, the mean age was 46 years, 79% werefemale, 84% were White, 13% were Black or African American, and 2% Asian. A total of 8% were

7

Intention-to-Treat1
Body Weight
Baseline mean (kg)% change frombaseline (LSMean)% difference
from placebo(LSMean) (95% CI)% of Patients losing
greater than or equal
to 5% body weight% difference fromplacebo (LSMean)(95% CI)% of Patients losing
greater than or equal
to 10% body weight% difference fromplacebo (LSMean)(95% CI)% of Patients losing
greater than or equal
to 15% body weight% difference fromplacebo (LSMean)(95% CI)

Study 2 (Obesityor overweight withcomorbidity)
PLACEBO WEGOVY®
N=655
N=1306

Study 4 (Obesityor overweight
Study 3 (Type 2
with comorbidity
diabetes with obesity undergoing intensiveor overweight)
lifestyle therapy)
PLACEBO WEGOVY® PLACEBO WEGOVY®
N=403
N=404
N=204
N=407

105.2

105.4

100.5

99.9

103.7

106.9

-2.4

-14.9

-3.4

-9.6

-5.7

-16.0

-12.4
(-13.3; -11.6)*
31.1

83.5

-6.2
(-7.3; -5.2)*
30.2

52.4
(48.1; 56.7)*
12.0

66.1

47.9
43.1
(39.8; 46.3)*

47.8

37.2
(30.7; 43.8)*
10.2

54.1
(50.4; 57.9)*
4.8

67.4

-10.3
(-11.8; -8.7)*

44.5

37.0
(28.9; 45.2)*
27.1

34.3
(28.4; 40.2)*
4.3

25.1
20.7
(15.7; 25.8)*

84.8

73.0
45.9
(38.0; 53.7)*

13.2

53.4
40.2
(33.1; 47.3)*

LSMean = least squares mean; CI = confidence interval
1T he intent-to-treat population includes all randomized patients. In Study 2, at week 68, the body weight was missing for7.2% and 11.9% of patients randomized to WEGOVY® and placebo, respectively. In Study 3, at week 68, the body weight
was missing for 4.0% and 6.7% of patients randomized to WEGOVY® and placebo, respectively. In Study 4, at week 68, thebody weight was missing for 8.4% and 7.4% of patients randomized to WEGOVY® and placebo, respectively. Missing data
were imputed from retrieved subjects of the same randomized treatment arm (RD-MI).
*p<0.0001 (unadjusted 2-sided) for superiority.

For Study 5, the primary efficacy parameter was mean percent change in body weight fromrandomization (week 20) to week 68.
From randomization (week 20) to week 68, treatment with WEGOVY® resulted in a statisticallysignificant reduction in body weight compared with placebo (Table 8). Because patients who
discontinued WEGOVY® during titration and those who did not reach the 2.4 mg weekly dose were
not eligible for the randomized treatment period, the results may not reflect the experience of patientsin the general population who are first starting WEGOVY®.

Wegovy ® (semaglutide) injection 2.4 mg

Intention-to-treat1
Body Weight
Baseline mean (kg)% change frombaseline (LSMean)% difference
from placebo(LSMean) (95% CI)% of Patients losing
greater than or equal
to 5% body weight% difference fromplacebo (LSMean)(95% CI)% of Patients losing
greater than or equal
to 10% body weight% difference fromplacebo (LSMean)(95% CI)% of Patients losing
greater than or equal
to 15% body weight% difference fromplacebo (LSMean)(95% CI)

one comorbidity or BMI 27-34.9 kg/m2
with at least two comorbidities)
WEGOVY®
WEGOVY®
PLACEBO
1.7 mg
2.4 mg
N=101
N=101
N=199
90.2

86.1

86.9

-2.1

-9.6

-13.2

-7.5
(-9.6; -5.4)*-11.1(-12.9; -9.2)*

72.8

84.0

53.3
(41.0; 65.6)*

64.5(54.8; 74.3)*

39.1

59.9

19.4

4.5

34.5
(23.9; 45.1)*
2.6

55.4
(47.3; 63.6)*

20.8

38.2

18.2
(9.8; 26.7)*

35.6(27.9; 43.3)*

LSMean = least squares mean; CI = confidence interval
1The intent-to-treat population includes all randomized patients. At baseline,
24.7% of patients had type 2 diabetes mellitus. At week 68, the body weight
was missing for 3%, 3%, and 1% of patients randomized to WEGOVY® 1.7 mg,
WEGOVY® 2.4 mg, and placebo, respectively. Missing data were imputed from
retrieved subjects of the same randomized treatment arm (RD-MI).
*p<0.0001 (unadjusted 2-sided) for superiority.

A reduction in body weight was observed with WEGOVY®
irrespective of age, sex, race, ethnicity, BMI at baseline, bodyweight (kg) at baseline, and level of renal function impairment.
The cumulative frequency distributions of change in body weight
are shown in Figure 5 and Figure 6 for Studies 2 and 3. One
way to interpret this figure is to select a change in body weightof interest on the horizontal axis and note the corresponding
proportions of patients (vertical axis) in each treatment group
who achieved at least that degree of weight loss. For example, notethat the vertical line arising from -10% in Study 2 intersects the
WEGOVY® and placebo curves at approximately 66%, and 12%,
respectively, which correspond to the values shown in Table 7.

Cumulative Frequency (%)

Cumulative Frequency (%)

WEGOVY®

PlaceboObserved data from in-trial period including imputed data for missing
observations (RD-MI).

The time courses of weight loss with WEGOVY® and placebo from baseline through week 68 are depicted in Figure 7, Figure 8 and
Figure 9.
Figure 7. Change from baseline (%) in body weight (Study 2 on left and Study 3 on right)
0
-2
-4
-6
-8
-10
-12
-14
-16
-18
-20

-2.8

-15.6

0 4 8 12 16 20

WEGOVY® 1306 1281
Placebo 655 641

28

1248
603

36 44
Weeks

WEGOVY

52

60

1203
549

-2.4

-14.9

Change in Body Weight (%)

Study 6 (BMI ≥35 kg/m2 with at least

Placebo

68 RD-MI1212 1306
577 655

0
-2
-4
-6
-8
-10
-12
-14
-16
-18
-20

0 4 8 12 16 20

WEGOVY® 404
Placebo 403

397
394

Placebo

®

28

392
383

36 44
Weeks

WEGOVY

®

52

60

381
367

-3.3

-3.4

-9.9

-9.6

68 RD-MI
388 404
376 403

PlaceboObserved values for patients completing each scheduled visit, and estimates with multiple imputations from retrieved dropouts (RD-MI)

Figure 8. Change from baseline (%) in body weight (Study 4 on left and Study 5a on right)
0
-2
-4
-6
-8
-10
-12
-14
-16
-18
-20

-5.8

-5.7

-16.5 -16.0

Change in Body Weight (%)

Table 9. Changes in Body Weight at Week 68 in Study 6
in East-Asian Patients (WEGOVY® 1.7 mg)

Figure 6. Change in body weight (%) from baseline toweek 68 (Study 3)
100
90
80
70
60
50
40
30
20
10
0
-40
-30 -20 -10
0
10
20
30
40
Change in body weight (%)

Observed data from in-trial period including imputed data for missing
observations (RD-MI).

0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 RD-MI
396
385
367
373 407
Weeks

WEGOVY® 407
Placebo 204

197

194

183

WEGOVY

0
-2
-4
-6
-8
-10
-12
-14
-16
-18
-20

0 4 8 12 16 20 24 28

WEGOVY® 803
Placebo

189 204

Placebo

®

803

535
268

36 44
Weeks

WEGOVY

®

52

60

521
254

-5.4

-5.0

-17.7

-17.4

68 RD-MI
520 535
250 268

PlaceboObserved values for patients completing each scheduled visit, and estimates with multiple imputations from retrieved dropouts (RD-MI)aChange from week 0 was not a primary endpoint in study 4. Dotted line indicates time of randomization. Randomized patients (shown) do not include 99 patients that
discontinued during the 20-week run-in period.

Figure 9. Change in body weight (%) from baseline to week 68 (Study 6 in East-Asian Patients)
0
-1.9
-2.1
-2
-4
-6
-8
-9.9 -9.6-10
Change in Body Weight (%)

For Study 6, the primary efficacy parameters were mean percent
change in body weight and the percentage of patients achieving
greater than or equal to 5% weight loss from baseline to week 68.
After 68 weeks, treatment with WEGOVY® 1.7 mg and 2.4 mg
resulted in a statistically significant reduction in body weightcompared with placebo. Greater proportions of patients treatedwith WEGOVY® achieved 5%, 10%, and 15% weight loss thanthose treated with placebo as shown in Table 9.

WEGOVY®

Change in Body Weight (%)

LSMean = least squares mean; CI = confidence interval
1902 patients were enrolled at week 0 with a mean baseline body weight of
106.8 kg. The intent-to-treat population includes all randomized patients. At
week 68, the body weight was missing for 2.8% and 6.7% of patients randomized
to WEGOVY® and placebo, respectively. Missing data were imputed from
retrieved subjects of the same randomized treatment arm (RD-MI).
*p<0.001 (unadjusted 2-sided) for superiority, controlled for multiplicity.

Figure 5. Change in body weight (%) from baseline toweek 68 (Study 2)
100
90
80
70
60
50
40
30
20
10
0
-40
-30 -20 -10
0
10
20
30
40
Change in body weight (%)

Change in Body Weight (%)

Table 8. C hanges in Body Weight at Week 68 in Study 5(Obesity or overweight with comorbidity after
20-week run-in)
WEGOVY®
N=8031
Body Weight (only randomized patients)
Mean at week 0 (kg)107.2
PLACEBOWEGOVY®
N=268
N=535
Body Weight
Mean at week 20 (SD) (kg)95.4 (22.7)
96.5 (22.5)% change from week 20 at
6.9-7.9
week 68 (LSMean)% difference from placebo-14.8(LSMean) (95% CI)(-16.0; -13.5)*

8

-12
-14
-16
-18
-20

-13.4

0 4 8 12 16 20

WEGOVY® 1.7 mg 101
WEGOVY® 2.4 mg 199
Placebo 101

99
198
101

98
197
100

WEGOVY® 1.7 mg

28

36
Weeks

44

52

60

97
191
99

WEGOVY® 2.4 mg-13.2

68 RD-MI
98
193
100

101
199
101

PlaceboObserved values for patients completing each scheduled visit and estimates with multiple imputations from retrieved dropouts (RD-MI). At baseline, 24.7% of
patients had type 2 diabetes mellitus.

Wegovy ® (semaglutide) injection 2.4 mg
Effect of WEGOVY ® on Anthropometry and Cardiometabolic Parameters in Adults

Changes in waist circumference and cardiometabolic parameters with WEGOVY® are shown in Table 10 for Studies 2, 3, and 4; inTable 11 for Study 5; and in Table 12 for Study 6.
Table 10. Changes in Anthropometry and Cardiometabolic Parameters at Week 68 in Studies 2, 3, and 4

Intention-to-Treat
Waist Circumference (cm)
Baseline
Changes from baseline (LSMean1)
Difference from placebo (LSMean)
Systolic Blood Pressure (mmHg)
Baseline
Changes from baseline (LSMean1)
Difference from placebo (LSMean)
Diastolic Blood Pressure (mmHg)2Baseline
Changes from baseline (LSMean1)
Difference from placebo (LSMean)Heart Rate2,3
Baseline
Changes from baseline (LSMean)
Difference from placebo (LSMean)
HbA1c (%)2
Baseline
Changes from baseline (LSMean1)
Difference from placebo (LSMean)
Total Cholesterol (mg/dL)2,4
Baseline
Percent Change from baseline (LSMean1)
Relative difference from placebo (LSMean)LDL Cholesterol (mg/dL)2,4
Baseline
Percent Change from baseline (LSMean1)
Relative difference from placebo (LSMean)
HDL (mg/dL)2,4
Baseline
Percent Change from baseline (LSMean1)
Relative difference from placebo (LSMean)
Triglycerides (mg/dL)2,4
Baseline
Percent Change from baseline (LSMean1)
Relative difference from placebo (LSMean)

Study 2 (Obesity or
Study 3 (Type 2 diabetes Study 4 (Obesity or overweight
overweight with
with obesity orwith comorbidity undergoingcomorbidity)
overweight)
intensive lifestyle therapy)
PLACEBO WEGOVY® PLACEBO WEGOVY® PLACEBOWEGOVY®
N=655
N=1306
N=403
N=404
N=204
N=407
114.8
-4.1

114.6
-13.5
-9.4

115.5
-4.5

114.5
-9.4
-4.9

111.8
-6.3

113.6
-14.6
-8.3

127
-1.1

126
-6.2
-5.1

130
-0.5

130
-3.9
-3.4

124
-1.6

124
-5.6
-3.9

80
-0.4

80
-2.8
-2.4

80
-0.9

80
-1.6
-0.7

81
-0.8

80
-3.0
-2.2

72
-0.7

72
3.5
4.3

76
-0.2

75
2.5
2.7

71
2.1

71
3.1
1.0

5.7
-0.2

5.7
-0.4
-0.3

8.1
-0.4

8.1
-1.6
-1.2

5.8
-0.3

5.7
-0.5
-0.2

192.1
0.1

189.6
-3.3
-3.3

170.8
-0.5

170.8
-1.4
-0.9

188.7
2.1

185.4
-3.9
-5.8

112.5
1.3

110.3
-2.5
-3.8

90.1
0.1

90.1
0.5
0.4

111.8
2.6

107.7
-4.7
-7.1

49.5
1.4

49.4
5.2
3.8

43.8
4.1

44.7
6.9
2.7

50.9
5.0

51.6
6.5
1.5

127.9
-7.3

126.2
-21.9
-15.8

159.5
-9.4

154.9
-22.0
-13.9

110.9
-6.5

107.9
-22.5
-17.0

Missing data were imputed from retrieved subjects of the same randomized treatment arm (RD-MI)
1Model based estimates based on an analysis of covariance model including treatment (and stratification factors for Study 3 only) as a factor and baseline value as acovariate
2 Not included in the pre-specified hierarchical testing (except HbA1c for Study 3)
3 Model based estimates based on a mixed model for repeated measures including treatment (and stratification factors for Study 3 only) as a factor and baseline
values as a covariate
4 Baseline value is the geometric mean

Table 11. M ean Changes in Anthropometry and Cardiometabolic Parameters in Study 5 (Obesity or overweightwith comorbidity after 20-week run-in)1

Waist Circumference (cm)
Systolic Blood Pressure (mmHg)
Diastolic Blood Pressure (mmHg)2Heart Rate2,3
HbA1c (%)2

Total Cholesterol (mg/dL)2,4
LDL Cholesterol (mg/dL)2,4
HDL Cholesterol (mg/dL)2,4
Triglycerides (mg/dL)2,4

PLACEBOWEGOVY®
N=268
N=535
Change from
Change from
Randomization
Randomization
Randomization (week 20) to week Randomization (week 20) to week
(week 20)68 (LSMean1)(week 20)68 (LSMean1)
104.7
3.3
105.5
-6.4
121
4.4
121
0.5
78
0.9
78
0.3
76
-5.3
76
-2.0
5.4
0.1
5.4
-0.1
% Change from
% Change from
Randomization
Randomization
Randomization(week 20)
Randomization(week 20)
(week 20)
(LSMean1)(week 20)
(LSMean1)
175.1
11.4
175.9
4.9
109.1
7.6
108.7
1.1
43.6
17.8
44.5
18.2
95.3
14.8
98.1
-5.6

Missing data were imputed from retrieved subjects of the same randomized treatment arm (RD-MI)
1Model based estimates based on an analysis of covariance model including treatment as a factor and baseline value as a covariate
2 Not included in the pre-specified hierarchical testing
3 Model based estimates based on a mixed model for repeated measures including treatment as a factor and baseline values as a covariate
4 Baseline value is the geometric mean

Difference
from placebo(LSMean)
-9.7
-3.9
-0.5
3.3
-0.2
Relativedifference
from placebo(LSMean)
-5.8
-6.1
0.3
-17.8

9

Wegovy ® (semaglutide) injection 2.4 mg

103.8
-1.8

101.4
-7.7
-5.9

103.8
-11.0
-9.3

133
-5.3

135
-10.8
-5.4

133
-10.8
-5.5

86
-2.2

85
-4.6
-2.4

83
-5.3
-3.1

73
2.4

73
4.4
2.0

73
6.3
3.9

6.4
0.0

6.4
-0.9
-0.9

6.4
-0.9
-0.9

203.1
0.8

203.3
-6.6
-7.3

197.2
-8.7
-9.4

123.3
-3.8

120.1
-10.1
-6.5

116.5
-14.6
-11.2

48.7
5.9

50.2
6.7
0.7

50.8
9.2
3.1

134.2
5.5

138.8
-19.5
-23.7

127.1
-21.2
-25.3

Missing data were imputed from retrieved subjects of the same randomized treatment arm (RD-MI). At baseline, 24.7% of patients had type 2 diabetes mellitus.
1Model based estimates based on an analysis of covariance model including treatment and type 2 diabetes status as factors and baseline value as a covariate
2Not included in the pre-specified hierarchical testing
3Model based estimates based on a mixed model for repeated measures including treatment and type 2 diabetes status as factors and baseline values as a covariate
4 Baseline value is the geometric mean

14.3 Weight Reduction and Long-Term MaintenanceStudy in Pediatric Patients Aged 12 Years andOlder with Obesity
Overview of Clinical Trial in Pediatric Patients
WEGOVY® was evaluated in a 68-week, double-blind, randomized,
parallel group, placebo-controlled, multi-center trial in 201
pubertal pediatric patients aged 12 years and older with BMI
corresponding to ≥95th percentile standardized for age andsex (Study 7) (NCT#04102189). After a 12-week lifestyle run-in
period (including dietary recommendations and physical activity
counseling), patients were randomized 2:1 to WEGOVY® once
weekly or placebo once weekly. WEGOVY® or matching placebo
was escalated to 2.4 mg or maximally tolerated dose during a
16-week period followed by 52 weeks on maintenance dose. Of
WEGOVY® -treated patients who completed the trial, 86.7% wereon the 2.4 mg dose at the end of the trial; for 5% of patients, 1.7
mg was the maximum tolerated dose.
The mean age was 15 years; 38% of patients were male; 79% wereWhite, 8% were Black or African American, 2% were Asian, and
11% were of other or unknown race; and 11% were of Hispanic or
Latino ethnicity. The mean baseline body weight was 108 kg, andmean BMI was 37 kg/m2.
Results
The proportions of patients who discontinued study drug were
10% for the WEGOVY® -treated group and 10% for the placebotreated group.
The primary endpoint was percent change in BMI from baseline
to week 68. After 68 weeks, treatment with WEGOVY® resulted ina statistically significant reduction in percent BMI compared withplacebo. Greater proportions of patients treated with WEGOVY®
achieved ≥5% reduction in baseline BMI than those treated withplacebo as shown in Table 13.

Table 13. C hanges in Weight and BMI at Week 68 in
Pediatric Patients with Obesity Aged 12
Years and Older in Study 7
PLACEBOWEGOVY®
Intention-to-Treata
N=67
N=134
BMI
Baseline mean (kg/m2)
35.7
37.7
% change from baseline in BMI (LSMean)
0.6
-16.1
% difference from placebo (LSMean)-16.7(95% CI)(-20.3; -13.2)*% of Patients with greater than or equal to
19.7
77.1
5% reduction in baseline BMIb
% difference from placebo (LSMean)
57.4% of Patients with greater than or equal to
7.7
65.1
10% reduction in baseline BMIb
% difference from placebo (LSMean)
57.5% of Patients with greater than or equal to
4.0
57.8
15% reduction in baseline BMIb
% difference from placebo (LSMean)
53.9
Body Weightb
Baseline mean (kg)
102.6
109.9
% change from baseline (LSMean)a
2.7
-14.7
% difference from placebo (LSMean)-17.4
LSMean = least squares mean; CI = confidence intervalaThe intention-to-treat population includes all randomized patients. Missing data
were imputed using available data according to value and timing of last available
observation on treatment and endpoint’s baseline value from retrieved subjects(RD-MI). At week 68, the BMI was missing for 2.2% and 7.5% of patientsrandomized to WEGOVY® and placebo, respectively.
b Parameters not included in the pre-specified hierarchical testing.
*p<0.0001 (unadjusted 2-sided) for superiority.

baseline through week 68 is depicted in Figure 10. The cumulative
frequency distribution of change in BMI is shown in Figure 11.
Figure 10. C hange from Baseline (%) in BMI in
Pediatric Patients with Obesity Aged 12
Years and Older in Study 7
42-0.1 0.6
0
-2
-4
-6
-8
-10
-12
-14
-16.2 -16.1
-16
-18
0
12
28
44 52
68 RD-MIWEGOVY® 134
119
131
131
131 134
Weeks

Change in BMI (%)

Intention-to-treat
Waist circumference (cm)
BaselineC hange from baseline (LSMean1)Difference from placebo (LSMean)
Systolic blood pressure (mmHg)2BaselineC hange from baseline (LSMean1)Difference from placebo (LSMean)
Diastolic blood pressure (mmHg)2BaselineC hange from baseline (LSMean1)Difference from placebo (LSMean)Heart Rate2,3
BaselineC hange from baseline (LSMean1)Difference from placebo (LSMean)
HbA1c (%)2
BaselineC hange from baseline (LSMean1)Difference from placebo (LSMean)
Total Cholesterol (mg/dL)2,4
BaselinePercent change from baseline (LSMean1)Relative difference from placebo (LSMean)LDL Cholesterol (mg/dL)2,4
Baseline
Percent change from baseline (LSMean1)Relative difference from placebo (LSMean)
HDL Cholesterol (mg/dL)2,4
BaselinePercent change from baseline (LSMean1)Relative difference from placebo (LSMean)
Triglyceride (mg/dL)2,4
BaselinePercent change from baseline (LSMean1)Relative difference from placebo (LSMean)

Study 6 (BMI ≥35 kg/m2 with at least one comorbidity or
BMI 27-34.9 kg/m2 with at least two comorbidities)
PLACEBOWEGOVY® 1.7 mg WEGOVY® 2.4 mg
N=101
N=101
N=199

Placebo

67

56

63

WEGOVY®

62

62

67

PlaceboObserved values for patients completing each scheduled visit, and estimateswith multiple imputations from retrieved dropouts (RD-MI)

Figure 11. C hange in BMI (%) from Baseline to Week 68
in Pediatric Patients with Obesity Aged 12
Years and Older in Study 7
100
90
80
70
60
50
40
30
20
10
0
-50

Cumulative Frequency (%)

Table 12. Mean Changes in Anthropometry and Cardiometabolic Parameters at Week 68 in Study 6 in East-AsianPatients (WEGOVY® 1.7 mg)

10
The time course of change in BMI with WEGOVY® and placebo from

-40

-30

-20
-10
0
Change in BMI (%)

WEGOVY®

10

20

PlaceboObserved data from in-trial period including imputed data for missing
observations (RD-MI)

Effect of WEGOVY ® on Anthropometry and Cardiometabolic
Parameters in Pediatric Patients with Obesity Aged 12 Years andOlder
Changes in waist circumference and cardiometabolic parameterswith WEGOVY® are shown in Table 14 for the study in pediatricpatients aged 12 years and older.

Wegovy ® (semaglutide) injection 2.4 mg
Table 14. Mean Changes in Anthropometry and Cardiometabolic Parameters in
Pediatric Patients with Obesity Aged 12 Years and Older in Study 71
PLACEBOWEGOVY®
N=67
N=134
Change from
Change from Difference
Baseline
Baseline from placeboBaseline(LSMean)Baseline(LSMean)(LSMean)
Waist Circumference (cm)2
107.3
-0.6
111.9
-12.7
-12.1
Systolic Blood Pressure (mmHg)2
120
-0.8
120
-2.7
-1.9
Diastolic Blood Pressure (mmHg)2
73
-0.8
73
-1.4
-0.6
Heart Rate3
76
-2.3
79
1.2
3.5
HbA1c (%)2,4
5.4
-0.1
5.5
-0.4
-0.2
% Change% Change
Relativefrom
fromdifference
Baseline
Baseline from placeboBaseline(LSMean)Baseline(LSMean)(LSMean)Total Cholesterol (mg/dL)2,5
160.1
-1.3
159.4
-8.3
-7.1
LDL Cholesterol (mg/dL)2,5
91.7
-3.6
89.8
-9.9
-6.6
HDL Cholesterol (mg/dL)2,5
43.3
3.2
43.7
8.0
4.7
Triglycerides (mg/dL)2,5
108.0
2.6
111.3
-28.4
-30.2

Hypersensitivity Reactions
Inform patients that serious hypersensitivity reactions have been reported during postmarketing use of
semaglutide, the active ingredient in WEGOVY®. Advise patients on the symptoms of hypersensitivity
reactions and instruct them to stop taking WEGOVY® and seek medical advice promptly if such
symptoms occur [see Warnings and Precautions (5.6)].
Diabetic Retinopathy Complications in Patients with Type 2 Diabetes
Inform patients with type 2 diabetes to contact their physician if changes in vision are experienced
during treatment with WEGOVY® [see Warnings and Precautions (5.7)].
Heart Rate Increase
Instruct patients to inform their healthcare providers of palpitations or feelings of a racing heartbeat
while at rest during WEGOVY® treatment [see Warnings and Precautions (5.8)].
Suicidal Behavior and Ideation
Advise patients to report emergence or worsening of depression, suicidal thoughts or behavior,
and/or any unusual changes in mood or behavior. Inform patients that if they experience suicidal
thoughts or behaviors, they should stop taking WEGOVY® [see Warnings and Precautions (5.9)].
Pregnancy
WEGOVY® may cause fetal harm. Advise patients to inform their healthcare provider of a known orsuspected pregnancy. Advise patients who are exposed to WEGOVY® during pregnancy to contact
Novo Nordisk at 1-877-390-2760 or www.wegovypregnancyregistry.com [see Use in Specific
Populations (8.1)].

1Parameters listed in the table were not included in the pre-specified hierarchical testing.
2Missing data were imputed using available data according to value and timing of last available observation on treatment

and endpoint’s baseline value from retrieved subjects (RD-MI). Model based estimates based on an analysis of covariancemodel including treatment and stratification groups (gender, Tanner stage group) and the interaction between stratificationgroups as factors and baseline value as a covariate.
3 Model based estimates based on a mixed model for repeated measures including treatment as a factor and baseline value
as a covariate all nested within visit.
4 For patients without type 2 diabetes at randomization (N=129 for WEGOVY® -treated patients and N=64 for placebotreated patients).
5 Baseline value is the geometric mean.

16 HOW SUPPLIED/STORAGE AND HANDLINGHow Supplied
WEGOVY® injection is a clear, colorless solution in a pre-filled, disposable, single-dose pen-injector
with an integrated needle. It is supplied in cartons containing 4 pen-injectors in the following
packaging configurations:
Total Strength per Total Volume0.25 mg/0.5 mL
0.5 mg/0.5 mL
1 mg/0.5 mL
1.7 mg/0.75 mL
2.4 mg/0.75 mL

NDC
0169-4525-14
0169-4505-14
0169-4501-14
0169-4517-14
0169-4524-14

Recommended Storage
Store the WEGOVY® single-dose pen in the refrigerator from 2°C to 8°C (36°F to 46°F). If needed,prior to cap removal, the pen can be kept from 8°C to 30°C (46°F to 86°F) up to 28 days. Do notfreeze. Protect WEGOVY® from light. WEGOVY® must be kept in the original carton until time ofadministration. Discard the WEGOVY® pen after use.
17 PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions
for Use).
Risk of Thyroid C-cell Tumors
Inform patients that semaglutide causes thyroid C-cell tumors in rodents and that the human relevanceof this finding has not been determined. Counsel patients to report symptoms of thyroid tumors (e.g.,a lump in the neck, hoarseness, dysphagia, or dyspnea) to their physician [see Boxed Warning andWarnings and Precautions (5.1)].
Acute Pancreatitis
Inform patients of the potential risk for acute pancreatitis. Instruct patients to discontinue WEGOVY®
promptly and contact their physician if pancreatitis is suspected (severe abdominal pain that may
radiate to the back, and which may or may not be accompanied by vomiting) [see Warnings andPrecautions (5.2)].
Acute Gallbladder Disease
Inform patients of the risk of acute gallbladder disease. Advise patients that substantial or rapid
weight loss can increase the risk of gallbladder disease, but that gallbladder disease may also
occur in the absence of substantial or rapid weight loss. Instruct patients to contact their healthcare
provider for appropriate clinical follow-up if gallbladder disease is suspected [see Warnings andPrecautions (5.3)].
Hypoglycemia
Inform patients of the risk of hypoglycemia and educate patients on the signs and symptoms ofhypoglycemia. Advise patients with diabetes mellitus on glycemic lowering therapy that they may
have an increased risk of hypoglycemia when using WEGOVY® and to report signs and/or symptomsof hypoglycemia to their healthcare provider [see Warnings and Precautions (5.4)].
Dehydration and Renal Impairment
Advise patients treated with WEGOVY® of the potential risk of dehydration due to gastrointestinal
adverse reactions and take precautions to avoid fluid depletion. Inform patients of the potential risk
for worsening renal function and explain the associated signs and symptoms of renal impairment,
as well as the possibility of dialysis as a medical intervention if renal failure occurs [see Warnings
and Precautions (5.5)].

11

Manufactured by:
Novo Nordisk A/S
DK-2880 Bagsvaerd
Denmark
For additional information about WEGOVY® contact:
Novo Nordisk Inc.
800 Scudders Mill Road
Plainsboro, NJ 08536
1-833-934-6891
Version: 4
WEGOVY® is a registered trademark of Novo Nordisk A/S.
PATENT INFORMATION:
http://www.novonordisk-us.com/products/product-patents.html© 2024 Novo Nordisk All rights reserved.
US24SEMO00360 March 2024

Wegovy ® (semaglutide) injection 2.4 mg Medication Guide
Medication Guide
WEGOVY® (wee-GOH-vee)(semaglutide) injection, for subcutaneous use
Read this Medication Guide and Instructions for Use before you start using WEGOVY® and eachtime you get a refill. There may be new information. This information does not take the place oftalking to your healthcare provider about your medical condition or your treatment.
What is the most important information I should know about WEGOVY®?
WEGOVY® may cause serious side effects, including:• Possible thyroid tumors, including cancer. Tell your healthcare provider if you get
a lump or swelling in your neck, hoarseness, trouble swallowing, or shortness of breath.
These may be symptoms of thyroid cancer. In studies with rodents, WEGOVY® and medicinesthat work like WEGOVY® caused thyroid tumors, including thyroid cancer. It is not known
if WEGOVY® will cause thyroid tumors or a type of thyroid cancer called medullary thyroid
carcinoma (MTC) in people.
• Do not use WEGOVY® if you or any of your family have ever had a type of thyroid cancer called
medullary thyroid carcinoma (MTC), or if you have an endocrine system condition called
Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
What is WEGOVY®?
• WEGOVY® is an injectable prescription medicine used with a reduced calorie diet andincreased physical activity:• to reduce the risk of major cardiovascular events such as death, heart attack, or stroke inadults with known heart disease and with either obesity or overweight.
• that may help adults and children aged 12 years and older with obesity, or some adults withoverweight who also have weight-related medical problems, to help them lose excess bodyweight and keep the weight off.
• WEGOVY® contains semaglutide and should not be used with other semaglutide-containing
products or other GLP-1 receptor agonist medicines.
• It is not known if WEGOVY® is safe and effective for use in children under 12 years of age.
Do not use WEGOVY® if:• you or any of your family have ever had a type of thyroid cancer called medullary thyroid
carcinoma (MTC) or if you have an endocrine system condition called Multiple Endocrine
Neoplasia syndrome type 2 (MEN 2).
• you have had a serious allergic reaction to semaglutide or any of the ingredients in WEGOVY®.
See the end of this Medication Guide for a complete list of ingredients in WEGOVY®.
Symptoms of a serious allergic reaction include:• swelling of your face, lips, tongue or throat • fainting or feeling dizzy• problems breathing or swallowing• very rapid heartbeat• severe rash or itching
Before using WEGOVY®, tell your healthcare provider if you have any other medical
conditions, including if you:• have or have had problems with your pancreas or kidneys.
• have type 2 diabetes and a history of diabetic retinopathy.
• have or have had depression or suicidal thoughts, or mental health issues.
• are pregnant or plan to become pregnant. WEGOVY® may harm your unborn baby. You shouldstop using WEGOVY® 2 months before you plan to become pregnant.
• Pregnancy Exposure Registry: There is a pregnancy exposure registry for women who
use WEGOVY® during pregnancy. The purpose of this registry is to collect information
about the health of you and your baby. Talk to your healthcare provider about how you cantake part in this registry or you may contact Novo Nordisk at 1-877-390-2760.
• are breastfeeding or plan to breastfeed. It is not known if WEGOVY® passes into your breast
milk. You should talk with your healthcare provider about the best way to feed your baby while
using WEGOVY®.
Tell your healthcare provider about all the medicines you take, including prescription
and over-the-counter medicines, vitamins, and herbal supplements. WEGOVY® may affect theway some medicines work and some medicines may affect the way WEGOVY® works. Tell yourhealthcare provider if you are taking other medicines to treat diabetes, including sulfonylureas orinsulin. WEGOVY® slows stomach emptying and can affect medicines that need to pass throughthe stomach quickly.
Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist
when you get a new medicine.

12

How should I use WEGOVY®?
• Read the Instructions for Use that comes with WEGOVY®.
• Use WEGOVY® exactly as your healthcare provider tells you to.
• Your healthcare provider should show you how to use WEGOVY® before you use
it for the first time.
• WEGOVY® is injected under the skin (subcutaneously) of your stomach (abdomen), thigh, or
upper arm. Do not inject WEGOVY® into a muscle (intramuscularly) or vein (intravenously).
• Change (rotate) your injection site with each injection. Do not use the same site for each
injection.
• Use WEGOVY® 1 time each week, on the same day each week, at any time of theday.
• Start WEGOVY® with 0.25 mg per week in your first month. In your second month, increase
your weekly dose to 0.5 mg. In the third month, increase your weekly dose to 1 mg. In the
fourth month, increase your weekly dose to 1.7 mg. In the fifth month onwards, your healthcare
provider may either maintain your dose at 1.7 mg weekly or increase your weekly dose to 2.4
mg.
• If you need to change the day of the week, you may do so as long as your last dose of
WEGOVY® was given 2 or more days before.
• If you miss a dose of WEGOVY® and the next scheduled dose is more than 2 days away (48hours), take the missed dose as soon as possible. If you miss a dose of WEGOVY® and the nextschedule dose is less than 2 days away (48 hours), do not administer the dose. Take your next
dose on the regularly scheduled day.
• If you miss doses of WEGOVY® for more than 2 weeks, take your next dose on the regularlyscheduled day or call your healthcare provider to talk about how to restart your treatment.
• You can take WEGOVY® with or without food.
• If you take too much WEGOVY®, you may have severe nausea, severe vomiting and severe low
blood sugar. Call your healthcare provider or go to the nearest hospital emergency room rightaway if you experience any of these symptoms.
What are the possible side effects of WEGOVY®?
WEGOVY® may cause serious side effects, including:• See “What is the most important information I should know about WEGOVY®?”• inflammation of your pancreas (pancreatitis). Stop using WEGOVY® and call yourhealthcare provider right away if you have severe pain in your stomach area (abdomen) that will
not go away, with or without vomiting. You may feel the pain from your abdomen to your back.
• gallbladder problems. WEGOVY® may cause gallbladder problems including gallstones.
Some gallbladder problems need surgery. Call your healthcare provider if you have any of thefollowing symptoms:• pain in your upper stomach (abdomen)• yellowing of skin or eyes (jaundice)• fever• clay-colored stools• increased risk of low blood sugar (hypoglycemia), especially those who also
take medicines to treat diabetes mellitus such as insulin or sulfonylureas. Low
blood sugar in patients with diabetes who receive WEGOVY® can be a serious side effect.
Talk to your healthcare provider about how to recognize and treat low blood sugar. You should
check your blood sugar before you start taking WEGOVY® and while you take WEGOVY®.
Signs and symptoms of low blood sugar may include:• dizziness or light-headedness • sweating• shakiness• blurred vision• slurred speech• weakness• anxiety• hunger• headache• irritability or mood changes• confusion or drowsiness• fast heartbeat• feeling jittery• kidney problems (kidney failure). In people who have kidney problems, diarrhea, nausea,
and vomiting may cause a loss of fluids (dehydration) which may cause kidney problems to getworse. It is important for you to drink fluids to help reduce your chance of dehydration.
• serious allergic reactions. Stop using WEGOVY® and get medical help right away, if you
have any symptoms of a serious allergic reaction including:• swelling of your face, lips, tongue or throat• severe rash or itching• very rapid heartbeat• problems breathing or swallowing• fainting or feeling dizzy• change in vision in people with type 2 diabetes. Tell your healthcare provider if you
have changes in vision during treatment with WEGOVY®.
• increased heart rate. WEGOVY® can increase your heart rate while you are at rest.
Your healthcare provider should check your heart rate while you take WEGOVY®. Tell yourhealthcare provider if you feel your heart racing or pounding in your chest and it lasts forseveral minutes.
• depression or thoughts of suicide. You should pay attention to any mental changes,
especially sudden changes in your mood, behaviors, thoughts, or feelings. Call your healthcare
provider right away if you have any mental changes that are new, worse, or worry you.
The most common side effects of WEGOVY® in adults or children aged 12 years andolder may include:• nausea• stomach (abdomen) pain • dizziness• gas• diarrhea• headache• feeling bloated• stomach flu• vomiting• tiredness (fatigue)• belching• heartburn• constipation • upset stomach• low blood sugar in • runny nose or sore throat						people with type 2 diabetes
Talk to your healthcare provider about any side effect that bothers you or does not go away. These
are not all the possible side effects of WEGOVY®.
Call your doctor for medical advice about side effects. You may report side effects to FDA at
1-800-FDA-1088.

Wegovy ® (semaglutide) injection 2.4 mg Medication Guide
General information about the safe and effective use of WEGOVY®.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide.
Do not use WEGOVY® for a condition for which it was not prescribed. Do not give WEGOVY® toother people, even if they have the same symptoms that you have. It may harm them. You can ask
your pharmacist or healthcare provider for information about WEGOVY® that is written for healthprofessionals.
What are the ingredients in WEGOVY®?
Active Ingredient: semaglutide
Inactive Ingredients: disodium phosphate dihydrate, 1.42 mg; sodium chloride, 8.25 mg; water
for injection; and hydrochloric acid or sodium hydroxide may be added to adjust pH.
This Medication Guide has been approved by the U.S. Food and Drug Administration.
Revised: 03/2024

Manufactured by: Novo Nordisk A/S, DK-2880 Bagsvaerd, Denmark
WEGOVY® is a registered trademark of Novo Nordisk A/S.
PATENT Information: http://novonordisk-us.com/products/product-patents.html
For more information, go to startWegovy.com or call 1-833-WEGOVY® -1.

© 2024 Novo Nordisk All rights reserved.
US24SEMO00360 March 202413

Wegovy ® (semaglutide) injection 2.4 mg Instructions For Use
Instructions for Use
WEGOVY®
(semaglutide) injection

14

Pull out to get started

WEGOVY® comes in five strengths:
0.25 mg / 0.5 mL

0.5 mg / 0.5 mL

1 mg / 0.5 mL

1.7 mg / 0.75 mL

2.4 mg / 0.75 mL

Before you use your WEGOVY® pen for the first time, talk to your healthcare provider or your caregiver about how to prepare and inject WEGOVY®
correctly.

Important information
Read this Instructions for Use before you start using WEGOVY®. This information
does not replace talking to your healthcare provider about your medical conditionor treatment.
• Your WEGOVY® pen is for 1 time use only. The WEGOVY® pen is for subcutaneous (under
the skin) use only.
• The dose of WEGOVY® is already set on your pen.
• The needle is covered by the needle cover and the needle will not be seen.
• Do not remove the pen cap until you are ready to inject.
• Do not touch or push on the needle cover. You could get a needle stick injury.
• Your WEGOVY® injection will start when the needle cover is pressed firmly against your skin.
• Do not remove the pen from your skin before the yellow bar in the pen window has stopped
moving. The medicine may appear on the skin or squirt from the needle and you may not getyour full dose of WEGOVY® if:• the pen is removed too early or• you have not pressed the pen firmly against the skin for the entire injection.
• If the yellow bar does not start moving or stops during the injection, contact your healthcare
provider or Novo Nordisk at startWegovy.com or call Novo Nordisk Inc. at 1-833-934-6891.
• The needle cover will lock when the pen is removed from your skin. You cannot stop the
injection and restart it later.
• People who are blind or have vision problems should not use the WEGOVY® pen without help
from a person trained to use the WEGOVY® pen.
How do I store WEGOVY®?
• Store the WEGOVY® pen in the refrigerator between 36°F to 46°F (2°C to 8°C).
• If needed, before removing the pen cap, WEGOVY® can be stored from 46°F to 86°F (8°C to30°C) in the original carton for up to 28 days.
• Keep WEGOVY® in the original carton to protect it from light.
• Do not freeze.
• Throw away the pen if WEGOVY® has been frozen, has been exposed to light or temperatures
above 86°F(30°C), or has been out of the refrigerator for 28 days or longer.
Keep WEGOVY® and all medicines out of the reach of children.
WEGOVY® pen parts
Expiration date(on the back) Check that WEGOVY®
has not expired.

Before use After use

Always check you have themedicine and dose that yourhealthcare provider prescribed.
Either:0.25 mg / 0.5 mL

0.5 mg / 0.5 mL

1 mg / 0.5 mL

1.7 mg / 0.75 mL

2.4 mg / 0.75 mL

Pen window
Check that WEGOVY® is clear andcolorless. Air bubbles are normal.
They do not affect your dose.

Pen window
Check that the yellow
bar has stopped
moving to make sure
you received yourfull dose.

Needle cover
Needle is hidden inside.

Needle coverlocks after use.

Pen cap
Remove it just before
you are ready to inject.

How to use your WEGOVY® pen
Do not use your WEGOVY® pen without receiving training
from your healthcare provider. Make sure that you or yourcaregiver know how to give an injection with the pen before you
start your treatment.
Read and follow the instructions so that you use yourWEGOVY® pen correctly:
Preparation
Step 1. Prepare for your injection.
• Supplies you will need to give your WEGOVY®
injection:• WEGOVY® pen• 1 alcohol swab or soap and water• 1 gauze pad or cotton ball
• 1 sharps disposable container for used WEGOVY® pens
• Wash your hands.
• Check your WEGOVY® pen.
Do not use your WEGOVY® pen if:•	The pen appears to have been used or any part of the pen
appears broken, for example if it has been dropped.
•	The WEGOVY® medicine is not clear and colorless through the
pen window.
• The expiration date (EXP) has passed.
Contact Novo Nordisk at 1-833-934-6891 if your WEGOVY® pen
fails any of these checks.
Step 2. Choose your injection site.
• Your healthcare provider can help you choose theinjection site that is best for you•	You may inject into your upper leg (front of thethighs), lower stomach (keep 2 inches away fromyour belly button) or upper arm.
• Do not inject into an area where the skin is tender,
bruised, red, or hard. Avoid injecting into areas withscars or stretch marks.
• You may inject in the same body area each week, butmake sure it is not in the same spot each time.
Clean the injection site with an alcohol swab or soap andwater. Do not touch the injection site after cleaning. Allow
the skin to dry before injecting.

Upper arms
StomachUpper legs

Wegovy ® (semaglutide) injection 2.4 mg Instructions For Use
Injection
Step 3. Remove pen cap.
• Pull the pen cap straight off your pen.

Click 1
The injection
starts.

Click 2
Keep applying pressure
until the yellow bar has
stopped moving.

Yellow bar has
stopped moving.
The injection iscomplete. Lift the
pen slowly.

Throw away pen
Step 5. Throw away (dispose of) pen.
Safely dispose of the WEGOVY® pen right away after eachuse. See “How do I throw away (dispose of) WEGOVY®
pens?”

15

When your sharps disposal container is almost full, you willneed to follow your community guidelines for the right way todispose of your sharps disposal container. There may be state or
local laws about how you should throw away used needles andsyringes. For more information about safe sharps disposal, andfor specific sharps disposal in the state that you live in, go to the
FDA’s website at http://www.fda.gov/safesharpsdisposal.
• Do not reuse the pen.
• Do not recycle the pen or sharps disposal container, or throw
them into household trash.
Important: Keep your WEGOVY® pen, sharps disposal
container and all medicines out of the reach of children.
How do I care for my pen?
Protect your pen• Do not drop your pen or knock it against hard surfaces.
• Do not expose your pen to any liquids.
• If you think that your pen may be damaged, do not try to fix it.
Use a new one.
• Keep the pen cap on until you are ready to inject. Your pen will
no longer be sterile if you store an unused pen without the cap,
if you pull the pen cap off and put it on again, or if the pen cap
is missing. This could lead to an infection.
If you have any questions about
WEGOVY®, go to startWegovy.com
or call Novo Nordisk Inc. at
1-833-WEGOVY® -1• What if blood appears after injection?
If blood appears at the injection site, press the site lightly with agauze pad or cotton ball.
Step 4. Inject WEGOVY®.
• Push the pen firmly against your skin and keep
applying pressure until the yellow bar has stopped
moving. If the yellow bar does not start moving, press thepen more firmly against your skin.
• You will hear 2 clicks during the injection.
• Click 1: the injection has started.
• Click 2: the injection is ongoing.
• If you have problems with the injection, refer to the“Troubleshooting” section.

Troubleshooting• If you have problems injecting, change to a more
firm injection site, such as upper leg, or upper arm
or consider standing up while injecting into the lower
stomach.
• If medicine appears on the skin or squirts from theneedle, make sure the next time you inject to keep
applying pressure until the yellow bar has stopped
moving. Then you can lift the pen slowly from yourskin.

Medicine

The injection takes
about 5-10
seconds.

How do I throw away (dispose of) WEGOVY® pens?
Put the used WEGOVY® pen in an FDA-cleared sharps disposal
container right away after use. Do not throw away (disposeof) the pen in your household trash.
If you do not have an FDA-cleared sharps disposal container,
you may use a household container that is:• made of a heavy-duty plastic,• able to be closed with a tight-fitting, puncture-resistant lid,
without sharps being able to come out,
• upright and stable during use,
• leak-resistant, and• properly labeled to warn of hazardous waste inside thecontainer.

Manufactured by:
Novo Nordisk A/S
Novo Allé
DK-2880 Bagsvaerd, Denmark
For information about WEGOVY®, go tostartWegovy.com or contact:
Novo Nordisk Inc.
800 Scudders Mill Road
Plainsboro, NJ 08536
1-833-WEGOVY® -1
Version: 2
WEGOVY® is a registered trademark of Novo Nordisk A/S.
PATENT Information: http://novonordisk-us.com/products/
product-patents.html
This Instructions for Use has been approvedby the U.S. Food and Drug Administration.
Revised: August 2022
© 2024 Novo Nordisk All rights reserved.
US24SEMO00360 March 2024