What are the contraindications for starting Glucagon-like peptide-1 (GLP-1) medications?

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Last updated: March 31, 2025View editorial policy

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From the Guidelines

GLP-1 receptor agonist medications should not be started in patients with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2, as these medications may increase the risk of thyroid C-cell tumors, as stated in the most recent and highest quality study 1.

Contraindications for GLP-1 Medications

The following are contraindications for starting GLP-1 medications:

  • Personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2, due to the increased risk of thyroid C-cell tumors 1
  • History of serious hyper-sensitivity reaction to the drug, as indicated in the 2018 ACC expert consensus decision pathway 1
  • Severe renal impairment or end-stage renal disease (ESRD), particularly for exenatide and lixisenatide, as noted in the 2018 ACC expert consensus decision pathway 1
  • Pregnancy and breastfeeding, due to insufficient safety data, as mentioned in the 2023 Obesity Reviews study 1

Cautions for GLP-1 Medications

The following are cautions for starting GLP-1 medications:

  • Use with caution in patients with a history of pancreatitis, as indicated in the 2023 Obesity Reviews study 1
  • Use with caution in patients with severe renal impairment or ESRD, particularly for liraglutide and semaglutide, as noted in the 2018 ACC expert consensus decision pathway 1
  • Use with caution in patients with a history of diabetic retinopathy, as rapid improvement in glucose control may temporarily worsen retinopathy, as mentioned in the 2018 Journal of the American College of Cardiology study 1
  • Use with caution in patients with prior gastric surgery, as GLP-1RAs may delay gastric emptying, as stated in the 2018 Journal of the American College of Cardiology study 1

From the FDA Drug Label

Personal or family history of MTC or in patients with MEN 2 (4). Serious hypersensitivity reaction to semaglutide or any of the excipients in OZEMPIC (4). TRULICITY is contraindicated in patients with a previous serious hypersensitivity reaction to dulaglutide or to any of the components of TRULICITY. SAXENDA is contraindicated during pregnancy because weight loss offers no potential benefit to a pregnant woman and may result in fetal harm [see Clinical Considerations].

The contraindications for starting GLP-1 medications are:

  • Personal or family history of Medullary Thyroid Carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
  • Serious hypersensitivity reaction to the medication or any of the excipients
  • Pregnancy, as weight loss offers no potential benefit to a pregnant woman and may result in fetal harm 2, 3, 4

From the Research

Contraindications for Starting GLP-1 Medications

  • GLP-1 receptor agonists are contraindicated in those with a history of medullary thyroid cancer 5
  • GLP-1 receptor agonists should be used with caution in patients with a history of pancreatitis of a known cause 5
  • The use of GLP-1 receptor agonists may increase the risk of pancreatitis, although some studies suggest that this risk may be lower than previously thought 6, 7
  • The risk of pancreatitis associated with GLP-1 agonists may be dose-dependent, with higher cumulative doses associated with a higher risk of developing pancreatitis 8
  • GLP-1 receptor agonists may also increase the risk of thyroid cancer, although the evidence for this is still limited and inconclusive 6
  • Patients with a history of diabetic ketoacidosis should avoid using SGLT2 inhibitors, which are often used in conjunction with GLP-1 receptor agonists 5

Special Considerations

  • Patients at risk for deterioration of existing diabetic retinopathy should be carefully monitored if treated with semaglutide, a type of GLP-1 receptor agonist 9
  • GLP-1 receptor agonists may increase the risk of biliary disease, such as cholelithiasis 9
  • Patients with a history of pancreatitis or pancreatic cancer should be carefully evaluated before starting GLP-1 receptor agonist therapy 6, 7, 8

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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