Contraindications to Semaglutide
Semaglutide is absolutely contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN2). 1, 2
Absolute Contraindications
- Medullary thyroid carcinoma (MTC)
- Personal history of MTC
- Family history of MTC
- Multiple Endocrine Neoplasia syndrome type 2 (MEN2) 1, 2
- Known hypersensitivity to semaglutide or any component of the formulation 1
Relative Contraindications and Cautions
Gastrointestinal Conditions
- Suspected or confirmed pancreatitis - Semaglutide has not been studied in patients with a history of pancreatitis 3
- History of cholelithiasis or cholecystitis - Use with caution due to increased risk of gallbladder disease 2, 4
- Clinically significant gastroparesis - May worsen symptoms due to delayed gastric emptying 2
- Prior gastric surgery - Requires careful consideration due to potential effects on absorption 2
Renal Considerations
- Severe renal impairment - Use with caution in patients with eGFR <30 mL/min/1.73m² 2, 5
- While dose adjustment may not be warranted based on pharmacokinetic studies 6, close monitoring is essential
Ophthalmic Concerns
- Pre-existing diabetic retinopathy - Requires careful monitoring due to risk of retinopathy complications, particularly with rapid glycemic improvement 2, 4
Other Important Considerations
Monitoring and Risk Mitigation
When initiating semaglutide in eligible patients:
- Gradual dose titration is essential to minimize gastrointestinal adverse effects 5
- Monitor for signs of pancreatitis - persistent severe abdominal pain that may radiate to the back, with or without vomiting 4
- Regular ophthalmologic examinations in patients with pre-existing diabetic retinopathy 4
- Monitor renal function - particularly after initiation and dose increases in patients with renal impairment 5
Common Adverse Effects
- Gastrointestinal effects - nausea, vomiting, diarrhea, constipation, abdominal pain 2
- Gallbladder disease - increased risk of cholelithiasis 4
- Hypoglycemia risk - particularly when used with insulin or insulin secretagogues 2
Clinical Pearls
- The contraindication regarding MTC and MEN2 is based on animal studies showing an increased risk of C-cell tumors 2
- Gradual dose escalation significantly reduces the risk of gastrointestinal side effects 5
- For oral semaglutide, administration instructions are critical - patients must take it on an empty stomach with no more than 4 oz of water and wait at least 30 minutes before eating or taking other medications 3
- The risk of diabetic retinopathy complications appears to be related to the rapid improvement in glycemic control rather than a direct effect of the medication 4