Important Safety Information — Semaglutide

SHED Protocol

WARNING: RISK OF THYROID C-CELL TUMORS

In rodents, semaglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether semaglutide causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined.

Semaglutide is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC and symptoms of thyroid tumors.

Indications

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index (BMI) of 30 kg/m2 or greater (obesity), or 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbid condition.

Contraindications

Personal or family history of medullary thyroid carcinoma (MTC)
Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
Known serious hypersensitivity to semaglutide or any of the excipients

Warnings and Precautions

Thyroid C-cell tumors: Monitor for symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, persistent hoarseness). If MTC is suspected, discontinue semaglutide and refer for evaluation.
Acute pancreatitis: Has been reported with GLP-1 receptor agonists. Discontinue promptly if pancreatitis is suspected. Do not restart if pancreatitis is confirmed.
Acute gallbladder disease: Events including cholelithiasis and cholecystitis have been reported. If gallbladder disease is suspected, gallbladder studies and appropriate clinical follow-up are indicated.
Hypoglycemia: Risk is increased when used with insulin secretagogues (e.g., sulfonylureas) or insulin. Consider lowering the dose of the concomitant insulin secretagogue or insulin to reduce the risk.
Acute kidney injury: Has been reported, usually in association with nausea, vomiting, and diarrhea leading to dehydration. Monitor renal function in patients with renal impairment reporting severe gastrointestinal reactions.
Diabetic retinopathy complications: Rapid improvement in glucose control may be associated with a temporary worsening of diabetic retinopathy. Monitor patients with a history of diabetic retinopathy.
Hypersensitivity reactions: Serious reactions including anaphylaxis and angioedema have been reported. Discontinue if suspected and treat promptly.
Suicidal behavior and ideation: Monitor for depression or suicidal thoughts. Discontinue if symptoms develop.
Pulmonary aspiration: Semaglutide delays gastric emptying. There is a risk of pulmonary aspiration during procedures requiring general anesthesia or deep sedation. Consider holding semaglutide before scheduled surgeries.

Common Side Effects

Nausea
Diarrhea
Vomiting
Constipation
Abdominal pain
Headache
Fatigue
Dyspepsia (indigestion)
Dizziness
Abdominal distension
Eructation (belching)
Flatulence
Gastroenteritis
Gastroesophageal reflux disease

Serious Side Effects

Seek medical attention immediately if you experience any of the following:

Severe, persistent abdominal pain, with or without vomiting (possible pancreatitis)
A lump or swelling in your neck, hoarseness, difficulty swallowing, or shortness of breath (possible thyroid tumor)
Signs of allergic reaction: rash, itching, swelling of the face, lips, tongue, or throat, difficulty breathing
Severe pain in the upper right abdomen (possible gallbladder problems)
Changes in vision (in patients with diabetes)
Decreased urination or dark-colored urine (possible kidney problems)
Rapid heartbeat
Depression or thoughts of self-harm

Drug Interactions

Insulin and insulin secretagogues: Increased risk of hypoglycemia. Consider dose reduction of the concomitant insulin or sulfonylurea.
Oral medications: Semaglutide delays gastric emptying, which may affect the absorption of concomitantly administered oral medications. Monitor the effect of oral medications when initiating or changing the dose of semaglutide.
Oral contraceptives: Delayed gastric emptying may reduce the efficacy of oral hormonal contraceptives. Patients should use an additional non-oral contraceptive method for 4 weeks after initiation and for 4 weeks after each dose increase.
Levothyroxine: Semaglutide may increase levothyroxine exposure. Monitor thyroid function.
Warfarin: Monitor INR when initiating or altering semaglutide therapy in patients taking warfarin.

Use in Specific Populations

Pregnancy: Contraindicated. Discontinue semaglutide at least 2 months before a planned pregnancy due to the long washout period. May cause fetal harm based on animal studies.
Lactation: Not recommended during breastfeeding. It is not known whether semaglutide is excreted in human breast milk.
Pediatric use: Safety and effectiveness have not been established in pediatric patients under 12 years of age.
Geriatric use: No overall differences in safety or efficacy observed in geriatric patients, though greater sensitivity of some older individuals cannot be ruled out.
Renal impairment: Monitor renal function in patients with renal impairment reporting gastrointestinal adverse reactions.
Hepatic impairment: No dose adjustment recommended, though limited data are available for severe hepatic impairment.