From the Guidelines
GLP-1 receptor agonists are contraindicated in patients with a history of serious hypersensitivity reaction to the drug, personal or family history of medullary thyroid cancer, Multiple Endocrine Neoplasia syndrome type 2 (MEN2), severe renal impairment, or end-stage renal failure, as well as in pregnancy or breastfeeding due to limited safety data 1. The contraindications for GLP-1 receptor agonists are primarily focused on patient safety and minimizing the risk of adverse effects.
- Patients with a personal or family history of medullary thyroid carcinoma (MTC) or MEN2 should avoid these medications due to the increased risk of thyroid C-cell tumors observed in animal studies 1.
- Individuals with a history of serious hypersensitivity reactions to any GLP-1 medication should not use them 1.
- Severe gastrointestinal disease, particularly gastroparesis, may worsen with GLP-1 use due to their effects on gastric emptying, and these medications should be used cautiously in patients with pancreatitis history as they may increase the risk of pancreatitis 1.
- Severe renal impairment requires dose adjustment or avoidance depending on the specific GLP-1 agent, with some agents like exenatide and lixisenatide being contraindicated in severe renal impairment or end-stage renal disease 1.
- Pregnancy and breastfeeding are relative contraindications due to limited safety data, and patients with diabetic retinopathy should be monitored closely as rapid glucose improvement may temporarily worsen retinopathy 1. These contraindications exist because GLP-1s work by enhancing glucose-dependent insulin secretion, slowing gastric emptying, and suppressing glucagon secretion, which can exacerbate certain underlying conditions.
- The use of GLP-1 receptor agonists should be carefully considered in patients with a history of pancreatitis, as they may increase the risk of pancreatitis, and dose adjustments may be necessary in patients with renal impairment 1.
- Additionally, patients with prior gastric surgery, including bariatric surgery, should be monitored closely when using GLP-1 receptor agonists, as they may experience delayed gastric emptying or other gastrointestinal side effects 1.
From the FDA Drug Label
Liraglutide is contraindicated in patients who have had a serious hypersensitivity reaction to liraglutide or any of the excipients in liraglutide [see Contraindications (4)]. TRULICITY is contraindicated in patients with a previous serious hypersensitivity reaction to dulaglutide or to any of the components of TRULICITY.
The contraindications to GLP-1s include:
- A history of serious hypersensitivity reaction to the specific GLP-1 receptor agonist (e.g., liraglutide or dulaglutide) or any of its components. No other direct contraindications to GLP-1s are mentioned in the provided drug labels 2 3.
From the Research
Contraindications to GLP-1s
- GLP-1 receptor agonists are contraindicated in those with a history of medullary thyroid cancer 4
- GLP-1 receptor agonists should be used with caution in patients with a history of pancreatitis of a known cause 4
- The use of GLP-1 RAs may be associated with an increased risk of pancreatitis, although the evidence is not conclusive 5, 6
- There is biological plausibility supporting an association between GLP-1 RA and medullary thyroid cancer (MTC) in rodents, but the evidence in humans is less clear 7
- Some studies have found a signal of increased reporting of thyroid cancer in patients treated with GLP-1 RAs, including medullary thyroid cancer and thyroid neoplasm 5, 8
- However, other studies have found no conclusive evidence of an elevated thyroid cancer risk associated with GLP-1 RA therapy 7, 6
- The risk of pancreatitis associated with GLP-1 RAs may be lower in comorbidity-free patients with type 2 diabetes 6