WEGOVY
semaglutide
Quick Facts
Used For
What WEGOVY Is Used For WEGOVY is used with diet and exercise: • To lower...
Common Side Effects
Serious Side Effects • Risk of Thyroid C-Cell Tumors • Acute Pancreatitis...
What You Should Know
Reading Your Medication Guide Read the Medication Guide and Instructions for Use that come with...
Prescription
Not Required
Generic Available
No
Indications and Usage
What WEGOVY Is Used For
WEGOVY is used with diet and exercise:
• To lower the risk of heart problems (heart attack, stroke) in adults who have heart disease and are overweight or have obesity.
• To help lose weight and keep it off long term in:
– Adults and teens ages 12 and older with obesity
– Adults who are overweight and have a weight-related health problem (like high blood pressure or diabetes)
Limitations of Use
• WEGOVY contains semaglutide. Do not use it with other semaglutide medicines or other GLP-1 medicines.
WEGOVY is indicated in combination with a reduced calorie diet and 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 cardiovascular disease and either obesity or overweight.
• to reduce excess body weight and maintain weight reduction long term in:
Limitations of Use
• WEGOVY contains semaglutide. Coadministration with other semaglutide-containing products or with any other GLP-1 receptor agonist is not recommended.
Dosage and Administration
Monitoring and Administration
• If you have type 2 diabetes, check your blood sugar before starting WEGOVY and while using it.
• Learn how to inject WEGOVY the right way before your first dose. Read the Instructions for Use that comes with your pen.
• Look at the medicine before each injection. Only use it if the liquid is clear, colorless, and has no particles.
• Use WEGOVY together with a reduced-calorie diet and more physical activity.
• Inject WEGOVY once a week on the same day each week. You can take it any time of day, with or without food.
• Inject WEGOVY under the skin in your stomach, thigh, or upper arm. You can change the time of day and injection site without changing your dose.
Adult Dosage
Start with 0.25 mg once a week for weeks 1 through 4. Then increase your dose every 4 weeks as shown below:
Weeks 1-4: 0.25 mg
Weeks 5-8: 0.5 mg
Weeks 9-12: 1 mg
Weeks 13-16: 1.7 mg
Week 17 and after: 1.7 mg or 2.4 mg
The recommended maintenance dose is 2.4 mg once weekly. Your doctor may choose 1.7 mg based on how you respond and tolerate the medicine.
Pediatric Dosage (12 Years and Older)
Follow this schedule:
Weeks 1-4: 0.25 mg
Weeks 5-8: 0.5 mg
Weeks 9-12: 1 mg
Weeks 13-16: 1.7 mg
Week 17 and after: 2.4 mg
If you cannot tolerate 2.4 mg, your doctor may lower your dose to 1.7 mg. Stop WEGOVY if you cannot tolerate 1.7 mg.
If You Miss a Dose
If you miss one dose and your next scheduled dose is more than 2 days away, take the missed dose as soon as possible. If your next dose is less than 2 days away, skip the missed dose and take your next dose on your regular day.
If you miss 2 or more doses in a row, take your next dose as scheduled or restart at a lower dose to reduce stomach problems.
2.1 Important Monitoring and Administration Instructions
• In patients with type 2 diabetes, monitor blood glucose prior to starting WEGOVY and during WEGOVY treatment [see Warnings 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 be changed without dose adjustment.
2.2 Recommended Dosage in Adults
Dosage Initiation and Escalation
• If patients do not tolerate a dose during dosage escalation, consider delaying dosage escalation for 4 weeks.
Treatment
Weeks
Once weekly Subcutaneous Dosage
Initiation
1 through 4
0.25 mg
Escalation
5 through 8
0.5 mg
9 through 12
1 mg
13 through 16
1.7 mg
Maintenance
17 and onward
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 the maintenance dosage [see Clinical Studies (14.2) ] .
Dosage Initiation and Escalation
• 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.
Treatment
Weeks
Once weekly Subcutaneous Dosage
Initiation
1 through 4
0.25 mg a
Escalation
5 through 8
0.5 mg a
9 through 12
1 mg a
13 through 16
1.7 mg b
Maintenance
17 and onward
2.4 mg
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 maintenance dosage, 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 more than 2 days away (48 hours), administer WEGOVY as soon as possible. If one dose is missed and the next scheduled dose is less 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 as scheduled or, if needed, reinitiate WEGOVY and follow the dose escalation schedule, which may reduce the occurrence of gastrointestinal symptoms associated with reinitiation of treatment.
Dosage Forms and Strengths
Injection
The medicine is a clear liquid that comes in 5 single-use 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
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
Contraindications
When NOT to Take WEGOVY
Do not take WEGOVY if you:
• Have or have a family history of thyroid cancer or a condition called MEN 2.
• Have had a serious allergic reaction to semaglutide or any other ingredient in WEGOVY. Serious allergic reactions like anaphylaxis and swelling have been reported.
WEGOVY 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 to any of the excipients in WEGOVY. Serious hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with WEGOVY [see Warnings and Precautions ( 5.6 )].
Warnings and Precautions
Risk of Thyroid Tumors
In animal studies, this medicine caused thyroid tumors. It is not known if it causes thyroid tumors in people. Do not use this medicine if you or your family have a history of certain thyroid problems. Tell your doctor if you notice a lump in your neck, trouble swallowing, trouble breathing, or a hoarse voice that does not go away.
Pancreatitis
This medicine can cause pancreas inflammation. This can be serious. Tell your doctor right away if you have severe stomach pain that does not go away, especially if it spreads to your back. Stop the medicine if pancreatitis is suspected.
Gallbladder Problems
This medicine can cause gallstones and gallbladder inflammation. Rapid weight loss can increase this risk. Tell your doctor if you have severe stomach pain, especially in the upper right area.
Low Blood Sugar
This medicine can lower blood sugar. If you have diabetes and take insulin or other diabetes medicines, your risk of low blood sugar is higher. Know the signs of low blood sugar like shakiness, sweating, or confusion. Check your blood sugar as directed by your doctor.
Kidney Problems
Kidney problems have been reported with this medicine. This can happen if you have nausea, vomiting, or diarrhea that causes dehydration. Tell your doctor if you have kidney problems or notice changes in urination.
Allergic Reactions
Serious allergic reactions can happen. Stop the medicine and get help right away if you have trouble breathing, swelling, or hives. Do not use this medicine if you had a prior allergic reaction to it.
Eye Problems in Diabetes Patients
If you have diabetes, this medicine may worsen eye problems. If you have a history of diabetic eye disease, see an eye doctor regularly. Rapid blood sugar improvement may temporarily worsen vision.
Increased Heart Rate
This medicine may increase your heart rate. Tell your doctor if you feel your heart racing or pounding while at rest. Your heart rate may be checked during treatment.
Mental Health Changes
Tell your doctor if you have depression, thoughts of hurting yourself, or unusual mood changes. Stop the medicine if you have suicidal thoughts.
5.1 Risk of Thyroid C-Cell Tumors
In mice and rats, semaglutide caused a dose-dependent and treatment-duration-dependent increase in the incidence of thyroid C-cell tumors (adenomas and carcinomas) after lifetime exposure at clinically relevant plasma exposures [see Nonclinical Toxicology ( 13.1 )] . It is unknown whether WEGOVY causes thyroid C-cell tumors, including MTC, in humans, as human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined.
Cases of MTC in patients treated with liraglutide, another GLP-1 receptor agonist, have been reported in the postmarketing period; the data in these reports are insufficient to establish or exclude a causal relationship between MTC and GLP-1 receptor agonist use in humans.
WEGOVY is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2. Counsel patients regarding the potential risk for MTC with the use of WEGOVY and inform them of symptoms of thyroid tumors (e.g. a mass in the neck, dysphagia, dyspnea, persistent hoarseness).
Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with 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 calcitonin values 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 or neck imaging should also be further evaluated.
5.2 Acute Pancreatitis
Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, including semaglutide. Acute pancreatitis was observed in patients treated with WEGOVY in clinical trials [see Adverse Reactions ( 6 )] . After initiation of WEGOVY, observe patients carefully for signs and symptoms of 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 is confirmed, 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 patients with a history of pancreatitis are at higher risk for development of pancreatitis on WEGOVY.
5.3 Acute Gallbladder Disease
Treatment with WEGOVY is associated with an increased occurrence of cholelithiasis and cholecystitis. The incidence of cholelithiasis 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-treated patients 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 pediatric patients aged 12 years and older, 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 patients and 0% placebo-treated patients [see Adverse Reactions ( 6.1)] .
Substantial or rapid weight loss can increase the risk of cholelithiasis; however, the incidence of acute gallbladder disease was greater in WEGOVY-treated patients than in placebo-treated patients, even after accounting for the degree of weight loss. If cholelithiasis 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 mass index (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 placebo-treated 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 patients treated 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 them on the signs and symptoms of hypoglycemia. In patients with diabetes, 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 risk of 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. Patients with renal impairment may be at greater risk of acute kidney injury, but some of these events have been reported in patients 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 [see Adverse 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 standard of 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 history of anaphylaxis or angioedema with another GLP-1 receptor agonist because it is unknown whether such patients will be predisposed to these reactions with WEGOVY.
5.7 Diabetic Retinopathy Complications in Patients with Type 2 Diabetes
In a trial of adult patients with type 2 diabetes and BMI greater than or equal to 27 kg/m 2 , 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 high cardiovascular risk, diabetic retinopathy complications (which was a 4-component adjudicated endpoint) occurred in patients treated with 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%) than among patients without a known history of diabetic retinopathy (semaglutide injection 0.7%, placebo 0.4%).
Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy. The effect of long-term glycemic control with semaglutide on diabetic retinopathy complications has not been studied. Patients with a history of diabetic retinopathy should be monitored for progression of diabetic retinopathy.
5.8 Heart Rate Increase
Treatment with WEGOVY was associated with increases in resting heart rate. Mean increases in resting heart rate of 1 to 4 beats per minute (bpm) were observed in WEGOVY-treated adult patients compared to placebo in clinical trials. More adult 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 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 clinical practice. 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 treated with WEGOVY for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Discontinue WEGOVY in patients who experience suicidal thoughts or behaviors. Avoid WEGOVY in patients with a history of suicidal attempts or active suicidal ideation.
Adverse Reactions
Serious Side Effects
• Risk of Thyroid C-Cell Tumors
• Acute Pancreatitis (sudden pancreas inflammation)
• Acute Gallbladder Disease
• Hypoglycemia (low blood sugar)
• Acute Kidney Injury (sudden kidney problems)
• Hypersensitivity Reactions (allergic reactions)
• Diabetic Retinopathy Complications in Patients with Type 2 Diabetes (eye problems)
• Heart Rate Increase (faster heartbeat)
• Suicidal Behavior and Ideation (thoughts of suicide)
Side Effects in Adults
WEGOVY was studied in over 2,100 adults with obesity for up to 68 weeks. About 7% of patients stopped taking WEGOVY due to side effects, compared to 3% on placebo (inactive pill). Common reasons for stopping were nausea, vomiting, and diarrhea.
Table: Common Side Effects (2% or more with WEGOVY vs. placebo)
| Side Effect | Placebo | WEGOVY |
|————-|———|——–|
| Nausea | 16% | 44% |
| Diarrhea | 16% | 30% |
| Vomiting | 6% | 24% |
| Constipation | 11% | 24% |
| Stomach pain | 10% | 20% |
| Headache | 10% | 14% |
| Tiredness | 5% | 11% |
| Indigestion | 3% | 9% |
| Dizziness | 4% | 8% |
| Bloating | 5% | 7% |
| Burping | <1% | 7% |
| Low blood sugar (in diabetes patients) | 2% | 6% |
Heart Safety Study
In a large heart study, 8,803 patients took WEGOVY for about 3 years. Sixteen percent stopped due to side effects, compared to 8% on placebo.
Side Effects in Teens (Ages 12 and Older)
WEGOVY was studied in 201 teens with obesity for 68 weeks.
Table: Common Side Effects (3% or more with WEGOVY vs. placebo)
| Side Effect | Placebo | WEGOVY |
|————-|———|——–|
| Nausea | 18% | 42% |
| Vomiting | 10% | 36% |
| Diarrhea | 19% | 22% |
| Headache | 16% | 17% |
| Stomach pain | 6% | 15% |
| Common cold | 10% | 12% |
| Dizziness | 3% | 8% |
| Stomach flu | 3% | 7% |
| Constipation | 2% | 6% |
Other Side Effects
Pancreas Inflammation (Acute Pancreatitis)
Confirmed in 4 WEGOVY patients (0.2 per 100 patient years) vs. 1 placebo patient.
Gallbladder Problems
Adults: Gallstones in 1.6% WEGOVY vs. 0.7% placebo. Gallbladder inflammation in 0.6% WEGOVY vs. 0.2% placebo.
Teens: Gallstones in 3.8% WEGOVY vs. 0% placebo.
Low Blood Sugar (Hypoglycemia)
Patients with Type 2 Diabetes: Clinically significant low blood sugar in 6.2% WEGOVY vs. 2.5% placebo. Risk was higher when taken with sulfonylurea diabetes medicine.
Patients without Diabetes: 3 episodes of serious low blood sugar were reported in the heart study with WEGOVY vs. 1 with placebo.
Kidney Problems
Kidney injury occurred in 7 adults taking WEGOVY (0.4 per 100 patient years) vs. 4 on placebo. Some cases linked to dehydration from stomach side effects.
Eye Problems in Diabetes Patients
Diabetic retinopathy (eye disease) reported in 4.0% WEGOVY vs. 2.7% placebo patients.
Heart Rate Increase
WEGOVY increased resting heart rate by 1-4 beats per minute. In teens, 54% had heart rate increases of 20+ beats per minute vs. 39% on placebo.
Low Blood Pressure and Fainting
Low blood pressure reported in 1.3% WEGOVY vs. 0.4% placebo. Fainting in 0.8% WEGOVY vs. 0.2% placebo.
Appendicitis
Occurred in 10 (0.5%) WEGOVY patients vs. 2 (0.2%) placebo patients.
Stomach and Gut Side Effects
Adults: 73% reported stomach problems with WEGOVY vs. 47% with placebo. Severe stomach problems in 4.1% WEGOVY vs. 0.9% placebo. Most common: nausea (44% vs. 16%), vomiting (25% vs. 6%), diarrhea (30% vs. 16%).
Teens: 62% reported stomach problems with WEGOVY vs. 42% placebo.
4.3% of adults stopped treatment due to stomach side effects.
Injection Site Reactions
1.4% WEGOVY vs. 1.0% placebo.
Allergic Reactions
Rash in 3% and hives in 3% of teens taking WEGOVY. Serious allergic reactions (anaphylaxis, swelling) have been reported.
Bone Fractures
More hip and pelvic fractures in women on WEGOVY (1.0%) vs. placebo (0.2%). More fractures in patients 75 and older: 2.4% WEGOVY vs. 0.6% placebo.
Kidney Stones
1.2% WEGOVY vs. 0.8% placebo.
Taste Changes
1.7% WEGOVY vs. 0.5% placebo.
Lab Tests
WEGOVY increased amylase (15-16%) and lipase (39%). Liver enzymes increased in some patients.
Reports After Drug Approval
Additional side effects reported after WEGOVY was approved:
• Pancreas inflammation, including severe cases and death
• Bowel blockage
• Serious allergic reactions (anaphylaxis, swelling)
• Sudden kidney injury
The following serious adverse reactions are described below or elsewhere in the prescribing information:
• Risk of Thyroid C-Cell Tumors [see Warnings and Precautions ( 5.1 )]
• Acute Pancreatitis [see Warnings and Precautions ( 5.2 )]
• 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 studies of 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 with obesity or overweight treated with 2.4 mg WEGOVY for up to 68 weeks and a 7 week off-drug follow-up period [see Clinical Studies (14.2) ] . Baseline characteristics included a mean age of 48 years, 71% female, 72% White, 14% Asian, 9% Black or African American, and 5% reported as other or unknown; and 85% were not Hispanic or Latino ethnicity, 13% were Hispanic or Latino ethnicity, and 2% reported as unknown. The baseline characteristics were 42% with hypertension, 19% with type 2 diabetes, 43% with dyslipidemia, 28% with a BMI greater than 40 kg/m 2 , 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 most common 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.
Placebo
N = 1,261
%
WEGOVY 2.4 mg
N = 2,116
%
Nausea
16
44
Diarrhea
16
30
Vomiting
6
24
Constipation
11
24
Abdominal Pain a
10
20
Headache
10
14
Fatigue b
5
11
Dyspepsia
3
9
Dizziness
4
8
Abdominal Distension
5
7
Eructation
<1
7
Hypoglycemia in T2DM c
2
6
Flatulence
4
6
Gastroenteritis
4
6
Gastroesophageal Reflux Disease
3
5
Gastritis d
1
4
Gastroenteritis Viral
3
4
Hair Loss
1
3
Dysesthesia e
1
2
a Includes abdominal pain, abdominal pain upper, abdominal pain lower, gastrointestinal pain, abdominal tenderness, abdominal discomfort and epigastric discomfort
c Defined as blood glucose <54 mg/dL with or without symptoms of hypoglycemia or severe hypoglycemia (requiring the assistance of another person) 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
e Includes paresthesia, hyperesthesia, burning sensation, allodynia, dysesthesia, skin burning sensation, pain of skin, and sensitive skin
In 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 Clinical Studies (14.1) ]. Safety data collection was limited to serious adverse events (including death), adverse events leading to discontinuation, and adverse events of special interest. Sixteen percent (16%) of WEGOVY-treated patients and 8% of placebo-treated patients, respectively, discontinued study drug due to an adverse event. Additional information from this trial is included in subsequent sections below when relevant.
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 Clinical Studies (14.3) ] . Baseline characteristics included a mean age of 15.4 years; 38% of patients were male; 79% were White, 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 107.5 kg, and mean BMI was 37 kg/m 2 .
Placebo
N = 67
% WEGOVY 2.4 mg
N = 133
%
Nausea
18
42
Vomiting
10
36
Diarrhea
19
22
Headache
16
17
Abdominal Pain
6
15
Nasopharyngitis
10
12
Dizziness
3
8
Gastroenteritis
3
7
Constipation
2
6
Gastroesophageal Reflux Disease
2
4
Sinusitis
2
4
Urinary tract infection
2
4
Ligament sprain
2
4
Anxiety
2
4
Hair Loss
0
4
Cholelithiasis
0
4
Eructation
0
4
Influenza
0
3
Rash
0
3
Urticaria
0
3
Other Adverse Reactions in Adults and/or Pediatric Patients
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 case of 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-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 pediatric patients aged 12 years and older [see Clinical Studies (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 patients and 0% placebo-treated patients.
Hypoglycemia
Patients with Type 2 Diabetes
In a trial of adult patients with type 2 diabetes and BMI greater than 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 placebo-treated 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 was reported in a WEGOVY-treated patient versus none in placebo-treated 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 mellitus, there was no systematic capturing or reporting of hypoglycemia.
In a cardiovascular outcomes trial in adult patients without type 2 diabetes, 3 episodes of serious hypoglycemia were reported in WEGOVY-treated patients versus 1 episode in placebo. Patients with 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 with dehydration in other clinical trials. The risk of renal adverse reactions with WEGOVY was increased in adult patients with a history of renal impairment (trials included 65 patients with a history of moderate or severe renal impairment at baseline), and occurred 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 greater than or equal to 27 kg/m 2 , 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 patients treated with placebo. The majority of events were reported as diabetic retinopathy (4.0%, 2.7%, and 2.7%, respectively) and non-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 treated with WEGOVY compared to placebo had maximum changes in heart 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 placebo-treated patients and syncope was reported in 0.8% of WEGOVY-treated patients versus 0.2% of placebo-treated patients. Some reactions were related to gastrointestinal adverse reactions and volume loss associated with WEGOVY. Hypotension and orthostatic hypotension were more frequently seen in patients on concomitant antihypertensive therapy. In a clinical trial in pediatric patients aged 12 years and older, hypotension was reported in 2.3% of WEGOVY-treated patients versus 0% in placebo-treated patients.
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 patients and 47% of patients receiving placebo reported gastrointestinal adverse reactions, including severe reactions that were reported more frequently among patients receiving WEGOVY (4.1%) than placebo (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, and hiccups. These reactions increased during dose escalation.
In the pediatric clinical trial, 62% of WEGOVY-treated patients and 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 a higher incidence than placebo among WEGOVY-treated pediatric patients included abdominal pain, constipation, eructation, gastroesophageal reflux disease, dyspepsia, and flatulence.
Permanent discontinuation of treatment as a result of a gastrointestinal adverse reaction occurred in 4.3% of WEGOVY-treated adult patients versus 0.7% of placebo-treated patients. In a 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 patients and 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 anti-semaglutide 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 placebo in female patients: 1.0% (24/2448) vs. 0.2% (5/2424), and in patients 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-treated patients and 0.8% of patients receiving placebo reported urolithiasis, including serious reactions that were reported more frequently among patients receiving WEGOVY (0.6%) than placebo (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 compared with 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 placebo-treated patients.
6.2 Postmarketing Experience
The following adverse reactions have been reported during post-approval use of semaglutide, the active ingredient of WEGOVY. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Gastrointestinal Disorders: acute pancreatitis and necrotizing pancreatitis, sometimes resulting in death; ileus
Hypersensitivity: anaphylaxis, angioedema, rash, urticaria
Renal and Urinary Disorders: acute kidney injury
Drug Interactions
Insulin or Sulfonylurea Medicines
WEGOVY lowers blood sugar and can cause low blood sugar (hypoglycemia). The risk of low blood sugar is higher when WEGOVY is used with insulin or sulfonylurea medicines (such as glyburide, glipizide, or glimepiride). When starting WEGOVY, your doctor may need to lower your insulin or sulfonylurea dose to reduce the risk of low blood sugar.
Oral Medicines
WEGOVY slows down stomach emptying. This may affect how other oral medicines work. In studies, WEGOVY did not affect the absorption of most oral medicines. Tell your doctor about all other medicines you take while using WEGOVY.
7.1 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 used in combination with insulin or insulin secretagogues (e.g., sulfonylureas). The addition of WEGOVY in patients treated with insulin has not been evaluated.
When initiating WEGOVY, 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 ) 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 absorption of orally administered medications [see Clinical Pharmacology ( 12.3 )] . Nonetheless, monitor the effects of oral medications concomitantly administered with WEGOVY.
Pregnancy
Pregnancy Exposure Registry
A pregnancy registry tracks pregnancies in women who took WEGOVY during pregnancy. Pregnant women taking WEGOVY and their doctors should call 1-877-390-2760 or go to www.wegovypregnancyregistry.com.
Risk Summary
Animal studies suggest possible risks to the unborn baby when the mother takes WEGOVY during pregnancy. Losing weight during pregnancy is not helpful and may harm the baby. If you become pregnant, your doctor will tell you about the risks and may have you stop taking WEGOVY. There is not enough information from human studies to know if WEGOVY causes birth defects, miscarriage, or other problems during pregnancy.
In pregnant animals given semaglutide, some babies died or had body changes. The mother animals also lost weight. These effects happened at different dose levels depending on the animal type.
In the U.S., about 2-4% of known pregnancies have major birth defects, and about 15-20% end in miscarriage.
Clinical Considerations
Maternal and Baby Risks
Gaining the right amount of weight during pregnancy is important for all pregnant women, including those who are already overweight or have obesity. This weight gain is needed for the mother’s body to support the growing baby.
Data
Animal Studies
In rats given semaglutide during pregnancy, some babies had growth problems and body changes. The mother rats ate less and lost weight.
In rabbits given semaglutide, some pregnancies ended early and babies had minor body changes. The mother rabbits also ate less and lost weight.
In monkeys given semaglutide, some pregnancies ended early and babies had spine and rib changes. The mother monkeys lost significant weight.
In another monkey study, early pregnancy losses occurred and the babies were smaller. The mother monkeys again lost significant weight.
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 1-877-390-2760 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 and may cause fetal harm. When a pregnancy is recognized, advise the pregnant 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 major birth 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 structural abnormalities were observed at below the MRHD (rabbit) and greater 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 and miscarriage for the indicated population are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Clinical Considerations
Disease-associated maternal and/or embryo/fetal risk
Appropriate weight gain based on pre-pregnancy weight is currently 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
Lactation
Risk Summary
There is no information about whether semaglutide passes into human breast milk. Studies in rats show the drug does pass into rat milk. If you are breastfeeding, talk with your doctor about whether to continue breastfeeding or take this medicine.
Data
In studies of nursing rats, semaglutide was found in the milk at levels 3 to 12 times lower than in the mother’s blood.
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 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 with the mother’s clinical need for WEGOVY and any potential adverse effects on the breastfed infant from WEGOVY or from the underlying maternal condition.
Data
In lactating rats, semaglutide was detected in milk at levels 3-12-fold lower than in maternal plasma.
Pediatric Use
Effectiveness for Patients 12 and Older
WEGOVY works for weight loss in patients 12 years and older with obesity. This was proven in a 68-week study of 201 patients. The study compared WEGOVY to a placebo (inactive pill).
Side Effects
Side effects in patients 12 years and older are similar to adults. But pediatric patients had more cases of gallbladder problems, rash, and hives compared to adults.
Patients with Type 2 Diabetes
There is not enough information to know if WEGOVY raises the risk of low blood sugar in pediatric patients with type 2 diabetes. Tell your doctor if you have symptoms of low blood sugar such as shakiness, sweating, or confusion. Your doctor should check your blood sugar before and during treatment. If you take insulin or other diabetes medicines, your doctor may need to lower your dose.
Younger Than 12 Years
WEGOVY has not been studied in patients younger than 12 years.
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 pediatric patients aged 12 years and older with obesity. Use of WEGOVY for this indication is supported by a 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 adult patients with obesity[see Clinical Studies(14.3)].
Adverse reactions with WEGOVY treatment in pediatric patients aged 12 years and older were generally 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 for obesity 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.
Geriatric Use
Older Patients in Studies
In the weight loss studies, 233 patients (9%) were ages 65 to 75, and 23 patients (1%) were 75 or older. In the heart disease study, 2,656 patients (30%) were ages 65 to 75, and 703 patients (8%) were 75 or older.
How Well It Works
Wegovy worked about the same for patients 65 and older as it did for younger patients.
Safety Concerns
In the heart disease study, patients 75 and older had more hip and pelvic fractures with Wegovy than with placebo. Patients 75 and older also had more serious health problems overall compared to younger patients.
Hepatic Impairment
No dose change of WEGOVY is needed for patients with kidney problems. Studies in patients with kidney problems, including severe kidney disease, showed no important change in how the medicine works in the body.
No dose adjustment of WEGOVY is recommended for patients with renal impairment. In a study in patients with renal impairment, including end-stage renal disease, no clinically relevant change in semaglutide pharmacokinetics was observed[see Clinical Pharmacology (12.3)].
Renal Impairment
Liver Problems
No dose change is needed for patients with liver problems. A study showed that the medicine works the same way in patients with different levels of liver problems.
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)].
Description
What is WEGOVY
WEGOVY (semaglutide) injection is given under the skin. It contains semaglutide, a man-made version of a natural hormone that helps control blood sugar and appetite.
How It Works
The drug is made using yeast. It attaches to a protein in the blood to stay in the body longer. It is also changed slightly so the body does not break it down too quickly.
The molecular formula is C187H291N45O59 and the molecular weight is 4113.58 g/mol.
What It Looks Like
WEGOVY is a clear, colorless liquid. It comes in a prefilled pen that you use to inject the medicine.
Strengths
Each 0.5 mL pen contains 0.25 mg, 0.5 mg, or 1 mg of semaglutide.
Each 0.75 mL pen contains 1.7 mg or 2.4 mg of semaglutide.
Other Ingredients
Each pen also contains:
– Disodium phosphate dihydrate, 1.42 mg
– Sodium chloride, 8.25 mg
– Water for injection
The pH is about 7.4, which is close to the pH of water. Hydrochloric acid or sodium hydroxide may be added to adjust the pH.
WEGOVY (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 in position 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 C 187 H 291 N 45 O 59 and the molecular weight is 4113.58 g/mol.
Figure 1. Structural Formula of semaglutide
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 mL of WEGOVY contains the following inactive ingredients: disodium phosphate dihydrate, 1.42 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.
Mechanism of Action
How This Medicine Works
Semaglutide is similar to a natural hormone in your body called GLP-1. It works by turning on GLP-1 receptors. These receptors are found in brain areas that control appetite and how much you eat.
Studies in animals show this medicine reaches brain regions that control food intake.
How it reduces heart disease risk is not fully understood.
How It Affects Your Body
Semaglutide helps you lose weight. It reduces body fat more than muscle. It works by decreasing how much you eat.
It also helps control blood sugar by increasing insulin and reducing glucagon. This effect only happens when blood sugar is high.
Semaglutide slows down how fast your stomach empties.
This medicine does not affect heart rhythm.
How Your Body Processes the Medicine
Absorption
About 89% of the medicine enters your blood. It reaches its highest level 1 to 3 days after a dose. You can inject it in the belly, thigh, or upper arm with similar results.
The steady state concentration is about 75 nmol/L in patients.
Distribution
The medicine spreads to about 12.5 liters of body water. It binds strongly to blood proteins (over 99%), which helps protect it from breaking down too fast.
How It Leaves the Body
The body clears the medicine at about 0.05 liters per hour. It stays in your system for about 5 to 7 weeks after the last dose.
The medicine is broken down through normal protein and fat processing. It leaves the body mainly through urine and feces. Only about 3% exits as intact drug in urine.
Special Populations
Kidney or liver problems do not significantly change how much medicine is in your blood.
Drug Interactions
This medicine slows stomach emptying. This may affect how other pills you take are absorbed. Studies at 1 mg dose showed no major interactions with other common medicines.
Immune Response
In studies, 3% of patients (50 out of 1,709) developed antibodies against semaglutide. Of these, 2% had antibodies that also reacted with natural GLP-1. These antibodies did not significantly affect medicine levels in the blood.
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/m 2 ) or overweight (BMI greater than or equal to 27 kg/m 2 ). 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 with obesity 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 the circulation 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 the peptide 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
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 in a 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 in subjects with overweight (BMI 27-29.9 kg/m 2 ) or obesity (BMI greater than or equal to 30 kg/m 2 ) and mild to moderate renal impairment, based on data from clinical trials.
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 hepatic function.
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 the rate of gastric emptying was observed with semaglutide 2.4 mg.
Figure 3. Impact of semaglutide 1 mg on the pharmacokinetics of co-administered medications
Relative exposure in terms of AUC and C max 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, C max : maximum concentration, CI: confidence interval.
12.6 Immunogenicity
The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other 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-treated patients, 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 to characterize the effects of anti-semaglutide antibodies on pharmacodynamics or effectiveness of semaglutide.
Patient Counseling Information
Reading Your Medication Guide
Read the Medication Guide and Instructions for Use that come with your medicine.
Thyroid Tumors
This medicine may cause thyroid tumors in animals. It is not clear if it causes tumors in humans. Tell your doctor if you have:
– A lump in your neck
– Hoarseness
– Trouble swallowing
– Trouble breathing
Pancreatitis
This medicine may cause pancreas problems. Stop taking this medicine and call your doctor right away if you have severe stomach pain that may spread to your back, with or without vomiting.
Gallbladder Problems
This medicine may cause gallbladder problems. Fast weight loss can increase this risk. But gallbladder problems can also happen without weight loss. Call your doctor if you think you have gallbladder problems.
Low Blood Sugar
This medicine may cause low blood sugar if you have diabetes. Know the signs of low blood sugar:
– Shaking
– Sweating
– Fast heartbeat
– Dizziness
– Hunger
Call your doctor if you have these symptoms.
Dehydration and Kidney Problems
This medicine may cause diarrhea, vomiting, or nausea. This can lead to dehydration. Dehydration can worsen kidney problems. Call your doctor if you have:
– Less urine than usual
– Swelling in your legs or feet
– Tiredness
Allergic Reactions
Serious allergic reactions may happen. Stop taking this medicine and get medical help right away if you have:
– Rash
– Itching
– Trouble breathing
– Swelling of face, lips, or throat
Eye Problems
If you have diabetes, call your doctor if you notice any changes in your vision during treatment.
Fast Heartbeat
Tell your doctor if you feel your heart racing or pounding while at rest.
Mental Health
Tell your doctor if you have:
– New or worsening depression
– Thoughts of hurting yourself
– Unusual mood changes
Stop taking this medicine if you have thoughts of hurting yourself.
Pregnancy
This medicine may harm an unborn baby. Tell your doctor if you become pregnant. If you take this medicine during pregnancy, call 1-877-390-2760 or visit www.wegovypregnancyregistry.com.
Made By
Novo Nordisk A/S
DK-2880 Bagsvaerd, Denmark
For More Information
Call 1-833-934-6891
Version: 4
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 relevance of 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 and Warnings 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 and Precautions ( 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 and Precautions ( 5.3 )].
Hypoglycemia
Inform patients of the risk of hypoglycemia and educate patients on the signs and symptoms of hypoglycemia. 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 symptoms of 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 )] .
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 or suspected 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 )] .
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
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References
WEGOVY (semaglutide) [prescribing information]. March 2026. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f5e548d0-cc79-4c34-a3f5-e20a5b8b6564
Accessed: March 27, 2026