Contraindications for Semaglutide Use
Semaglutide is absolutely contraindicated in patients with personal or family history of medullary thyroid carcinoma (MTC), multiple endocrine neoplasia syndrome type 2 (MEN2), and history of serious hypersensitivity reactions to the drug. 1, 2
Absolute Contraindications
- Personal or family history of medullary thyroid carcinoma (MTC) 1, 2
- Multiple endocrine neoplasia syndrome type 2 (MEN2) 1, 2
- History of serious hypersensitivity reaction to semaglutide 1, 3
- Pregnancy or breastfeeding 2, 4
Relative Contraindications and Cautions
Renal Considerations
- Exenatide and lixisenatide (other GLP-1 RAs) are not recommended in severe renal impairment or end-stage renal disease (ESRD), but semaglutide can be used with caution in these patients 2
- Patients with severe renal impairment require careful monitoring due to increased risk of gastrointestinal side effects and potential dehydration 3
Gastrointestinal Considerations
- Use with caution in patients with history of pancreatitis 2, 5
- Not recommended in patients with clinically meaningful gastroparesis 2, 3
- Use with caution in patients with prior gastric surgery 2, 3
Ophthalmologic Considerations
- Patients with history of diabetic retinopathy should be monitored closely for progression, as semaglutide has been associated with diabetic retinopathy complications 1, 2
- This risk is particularly increased in patients with rapid and marked glucose and A1C reductions 2, 3
Drug Interactions
- Increased risk of hypoglycemia when used with insulin or insulin secretagogues (e.g., sulfonylureas); dose reduction of these medications may be required 1, 2
- May delay absorption of concomitantly administered oral medications due to delayed gastric emptying 2, 3
- For patients using oral hormonal contraceptives, consider switching to a non-oral contraceptive method or adding a barrier method during initiation and dose escalation 3
Monitoring Recommendations
- Monitor for signs and symptoms of pancreatitis (persistent severe abdominal pain, sometimes radiating to the back, with or without vomiting) 1, 5
- If pancreatitis is suspected, discontinue semaglutide and do not restart if pancreatitis is confirmed 1, 5
- Monitor renal function, especially in patients experiencing severe gastrointestinal side effects that could lead to dehydration 3
- Monitor for gallbladder disease due to increased risk of cholelithiasis 3, 5
- Monitor patients with history of diabetic retinopathy for progression 1, 3
- Monitor thyroid function in patients on thyroid replacement therapy, as semaglutide may affect thyroid hormone levels 6
Clinical Pearls and Pitfalls
- Semaglutide carries an FDA Black Box Warning regarding the risk of thyroid C-cell tumors based on rodent studies 1, 2
- Routine monitoring of serum calcitonin or thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with semaglutide 1
- Slow dose titration when initiating semaglutide minimizes gastrointestinal side effects 3, 7
- Never share semaglutide pens between patients, even if the needle is changed, due to risk of blood-borne pathogen transmission 1
- For patients requiring surgery, be aware of potential anesthetic risks related to delayed gastric emptying 4