Contraindications to Semaglutide
Semaglutide has two absolute contraindications: personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2), and known hypersensitivity to semaglutide or any product components. 1
Absolute Contraindications
- Personal or family history of medullary thyroid carcinoma (MTC) - This carries an FDA Black Box Warning based on rodent studies showing thyroid C-cell tumors 2, 1
- Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) - Absolute contraindication per FDA labeling 2, 1, 3
- Known hypersensitivity to semaglutide or product components - Risk of severe allergic reactions 1
- Pregnancy or breastfeeding - Safety has not been established in these populations 2, 4, 5
Relative Contraindications and High-Risk Situations Requiring Extreme Caution
Gastrointestinal Conditions
- Clinically meaningful gastroparesis - Semaglutide delays gastric emptying and will worsen symptoms; not recommended in these patients 2
- Active or suspected pancreatitis - Not recommended; increased risk of pancreatitis exists 2, 3
- History of pancreatitis - Use with caution; semaglutide has not been adequately studied in this population 3
Ophthalmologic Concerns
- Diabetic retinopathy - Close monitoring required for progression, particularly when combined with insulin, due to increased risk of retinopathy complications from rapid glycemic improvement 2, 6
Renal Impairment
- Severe renal impairment or end-stage renal disease - Can be used with caution (unlike exenatide which is contraindicated at eGFR <30 mL/min/1.73 m²), but requires careful monitoring for gastrointestinal side effects leading to dehydration and acute kidney injury 2, 5
Pre-Surgical Considerations
- Upcoming procedures requiring anesthesia - Ensure adequate fasting periods due to delayed gastric emptying and increased aspiration risk 4, 5
Important Drug Interactions Requiring Dose Adjustments
- Concurrent insulin or insulin secretagogues (sulfonylureas, glinides) - Significantly increased hypoglycemia risk; dose reduction of these medications is required when initiating semaglutide 2, 4
- Oral contraceptives - Consider switching to non-oral contraceptive method or adding barrier method for 4 weeks after initiation and each dose escalation due to delayed gastric emptying affecting absorption 2
Common Pitfalls to Avoid
- Do not confuse with Hashimoto's thyroiditis - This autoimmune condition is NOT a contraindication; only medullary thyroid cancer and MEN 2 are contraindicated 4
- Monitor for gallbladder disease - Increased risk of cholelithiasis and cholecystitis requiring ongoing surveillance 2, 4, 7
- Renal function monitoring - Essential when initiating or escalating doses, especially with severe gastrointestinal reactions that could cause dehydration 2
- Slow dose titration is mandatory - Start at 0.25 mg weekly for 4 weeks to minimize gastrointestinal side effects (nausea, vomiting, diarrhea) which are the most common adverse effects 4, 3