Contraindications for GLP-1 Receptor Agonists
GLP-1 receptor agonists are absolutely contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2), and in those with a history of serious hypersensitivity reactions to the specific drug. 1, 2, 3, 4
Absolute Contraindications
Personal or family history of medullary thyroid carcinoma (MTC) - This is a black box warning based on rodent studies showing thyroid C-cell tumors, though human evidence remains inconclusive 1, 2, 3, 4, 5
Multiple endocrine neoplasia syndrome type 2 (MEN2) - Patients with this genetic syndrome are at increased risk for MTC 1, 2
History of serious hypersensitivity reaction to the specific GLP-1 receptor agonist - Including anaphylaxis or angioedema to that particular drug 3, 4
Severe renal impairment or end-stage renal disease (ESRD) - This applies specifically to exenatide and lixisenatide; liraglutide and semaglutide can be used with caution in this population 1
Important Clinical Cautions (Not Absolute Contraindications)
Pancreatitis History
- Use liraglutide with caution in patients with a history of pancreatitis 1
- Acute pancreatitis has been reported with GLP-1 receptor agonists, though causality remains uncertain 3, 4, 6
- If pancreatitis is suspected during treatment, discontinue the drug immediately and do not restart if confirmed 3, 4
Renal Impairment
- Liraglutide and semaglutide should be used with caution in severe renal impairment or ESRD 1
- Acute kidney injury has been reported, primarily due to severe gastrointestinal losses causing dehydration 3, 4, 6
- Monitor renal function when initiating or escalating doses, especially in patients with severe GI symptoms 3, 4
Hypoglycemia Risk
- Risk increases when combined with insulin or insulin secretagogues (sulfonylureas) - dose reduction of these agents may be required 1, 3, 4
- GLP-1 receptor agonists alone have a low intrinsic hypoglycemia risk due to glucose-dependent mechanism 1, 6, 7
Gastrointestinal Considerations
- Shorter-acting agents delay gastric emptying and are not recommended in patients with clinically meaningful gastroparesis 1
- Exercise caution in patients with prior gastric surgery 1
- Perioperative concern: Delayed gastric emptying may increase aspiration risk during general anesthesia or deep sedation 1, 4
Diabetic Retinopathy
- Semaglutide has been associated with diabetic retinopathy complications, particularly in patients with pre-existing retinopathy, likely related to rapid glucose reduction 1, 3
- Monitor patients with a history of diabetic retinopathy for progression 3
Gallbladder Disease
- Acute gallbladder events (cholelithiasis, cholecystitis) have been reported with GLP-1 receptor agonists 4
- If cholelithiasis is suspected, obtain gallbladder studies and appropriate follow-up 4
Common Pitfalls to Avoid
Do not confuse the thyroid cancer contraindication: Only MTC and MEN2 are contraindications; Hashimoto's thyroiditis is NOT a contraindication and these drugs can be safely used 2
Cross-reactivity concern: Use caution in patients with prior anaphylaxis or angioedema to another GLP-1 receptor agonist, as cross-reactivity is possible though not definitively established 3, 4
Pregnancy: All GLP-1 receptor agonists are contraindicated in women who are or may become pregnant 1
Pen-sharing: Never share pens between patients even with needle changes due to blood-borne pathogen transmission risk 3, 4