Brand Names

OZEMPIC
RYBELSUS
SEMAGLUTIDE
WEGOVY
WEGOVY HD

Boxed Warning

• In rodents, semaglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether WEGOVY causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined [see Warnings and Precautions ( 5.1 ), Nonclinical Toxicology ( 13.1 )]. • WEGOVY is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) [see Contraindications ( 4 )]. 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 [see Contraindications ( 4 ), Warnings and Precautions ( 5.1 )].

Indications and Usage

WEGOVY injection is indicated in combination with a reduced calorie diet and increased physical activity: • to reduce the risk of major adverse cardiovascular (CV) events (CV death, non-fatal myocardial infarction, or non-fatal stroke) in adults with established CV disease and either obesity or overweight. • to reduce excess body weight and maintain weight reduction long term in: o adults and pediatric patients aged 12 years and older with obesity. o adults with overweight in the presence of at least one weight-related comorbid condition. • for the treatment of noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (NASH), with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis) in adults. This indication is approved under accelerated approval based on improvement of MASH and fibrosis [see Clinical Studies (14.4)]. Continued approval for this indication may be contingent upon the verification and description of clinical benefit in a confirmatory trial. WEGOVY tablets are indicated in combination with a reduced calorie diet and increased physical activity: • to reduce the risk of major adverse CV events (CV death, non-fatal myocardial infarction, or non-fatal stroke) in adults with established CV disease and either obesity or overweight. • to reduce excess body weight and maintain weight reduction long term in adults with obesity, or in adults with overweight in the presence of at least one weight-related comorbid condition. Limitations of Use Concomitant use of WEGOVY (semaglutide) tablets or WEGOVY (semaglutide) injection with other semaglutide-containing products or with any other GLP-1 receptor agonist is not recommended.

Contraindications

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 injection or WEGOVY tablet. Serious hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with WEGOVY [see Warnings and Precautions (5.7)].

Adverse Reactions

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 Due to Volume Depletion [see Warnings and Precautions (5.5)] •Severe Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.6)] •Hypersensitivity Reactions [see Warnings and Precautions (5.7)] •Diabetic Retinopathy Complications in Patients with Type 2 Diabetes [see Warnings and Precautions (5.8)] •Heart Rate Increase [see Warnings and Precautions (5.9)] •Pulmonary Aspiration During General Anesthesia or Deep Sedation [see Warnings and Precautions ( 5.10 )]

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 semaglutide in CV risk reduction in adults has not been established. For treatment of MASH in humans, the precise mechanism of action of semaglutide is not fully understood and may involve multiple pathways mediated by weight loss and other factors. In a mouse model of diet-induced MASH, treatment with semaglutide resulted in histological improvements in steatosis, inflammation, and fibrosis in liver compared to baseline, which was associated with body weight loss, intermittent periods of reduced food intake, and improvements in relevant biomarkers. The relationship between the pathophysiology of MASH in animal models and humans has not been fully established.

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 event of 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 period of observation and treatment for these symptoms may be necessary, taking into account the long half-life of WEGOVY of approximately 1 week.

⚠ Caution

Medical Disclaimer: This information is for educational purposes only. Always consult a healthcare professional before taking any medication.