Is it safe to use GLP-1 (Glucagon-like peptide-1) receptor agonists in a patient with stage three CKD, history of gallstone pancreatitis, and family history of medullary thyroid cancer?

From the Guidelines

GLP-1 receptor agonists should be used with extreme caution in this patient due to multiple risk factors, and alternative diabetes medications like DPP-4 inhibitors, SGLT2 inhibitors (if eGFR permits), or insulin might be safer options. For stage three CKD, dose adjustments are typically needed for exenatide (avoid if eGFR <30) while liraglutide, dulaglutide, and semaglutide can be used without dose adjustment in moderate renal impairment, as stated in the 2022 study by the American Diabetes Association and Kidney Disease: Improving Global Outcomes 1. However, the history of gallstone pancreatitis is concerning as GLP-1 agonists may increase the risk of pancreatitis and gallbladder disease, as noted in the 2018 ACC expert consensus decision pathway on novel therapies for cardiovascular risk reduction in patients with type 2 diabetes and atherosclerotic cardiovascular disease 1. Most importantly, the family history of medullary thyroid cancer represents a significant contraindication, particularly for long-acting GLP-1 agonists, as these medications carry a boxed warning about the risk of thyroid C-cell tumors, as highlighted in the 2025 standards of care in diabetes by the American Diabetes Association 1. Before considering any GLP-1 agonist, the patient should undergo thorough thyroid screening and genetic testing for RET proto-oncogene mutations if medullary thyroid cancer is in the immediate family. A comprehensive risk-benefit discussion with the patient and consultation with endocrinology and nephrology specialists would be advisable before making a treatment decision, taking into account the patient's complex medical history and the potential risks and benefits of GLP-1 receptor agonists, as emphasized in the 2021 synopsis of the 2020 KDIGO clinical practice guideline on diabetes management in chronic kidney disease 1.

Some key points to consider:

• The patient's stage three CKD requires careful consideration of the potential risks and benefits of GLP-1 receptor agonists, as well as the need for dose adjustments or alternative medications.
• The history of gallstone pancreatitis increases the risk of pancreatitis and gallbladder disease with GLP-1 agonists, and alternative medications may be safer options.
• The family history of medullary thyroid cancer is a significant contraindication for long-acting GLP-1 agonists, and thorough thyroid screening and genetic testing are necessary before considering these medications.
• A comprehensive risk-benefit discussion and consultation with specialists are essential to determine the best course of treatment for this patient.

In terms of specific medications, the 2022 study by the American Diabetes Association and Kidney Disease: Improving Global Outcomes 1 notes that GLP-1 receptor agonists like liraglutide, dulaglutide, and semaglutide can be used without dose adjustment in moderate renal impairment, but exenatide requires dose adjustments and is contraindicated if eGFR <30. The 2025 standards of care in diabetes by the American Diabetes Association 1 also highlight the potential risks and benefits of GLP-1 receptor agonists, including the risk of thyroid C-cell tumors and the need for thorough thyroid screening and genetic testing. Overall, the use of GLP-1 receptor agonists in this patient requires careful consideration of the potential risks and benefits, as well as consultation with specialists and a comprehensive risk-benefit discussion.

From the FDA Drug Label

OZEMPIC is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

• Personal or family history of medullary thyroid carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2 (4).

Has not been studied in patients with a history of pancreatitis. Consider another antidiabetic therapy (1,5.2).

The use of GLP-1 receptor agonists, such as semaglutide, is contraindicated in patients with a family history of medullary thyroid cancer. Additionally, the drug has not been studied in patients with a history of pancreatitis, and another antidiabetic therapy should be considered. Therefore, it is not safe to use GLP-1 receptor agonists in this patient due to the family history of medullary thyroid cancer and history of gallstone pancreatitis 2.

From the Research

Safety of GLP-1 Receptor Agonists in Patients with Stage Three CKD, History of Gallstone Pancreatitis, and Family History of Medullary Thyroid Cancer

• The use of GLP-1 receptor agonists in patients with stage three chronic kidney disease (CKD) may be beneficial, as these agents have been shown to confer protection against major cardiovascular disease and reduce the risk of admission to hospital for heart failure 3.
• However, GLP-1 receptor agonists are contraindicated in patients with a history of medullary thyroid cancer, and caution is advised in patients with a history of pancreatitis of a known cause 3.
• Studies have investigated the association between GLP-1 receptor agonists and pancreatitis, with some meta-analyses suggesting no significant increase in risk 4, 5.
• However, other studies have reported a potential increased risk of cholelithiasis associated with GLP-1 receptor agonist therapy 5.
• Regarding the risk of thyroid cancer, some studies have suggested a potential association between GLP-1 receptor agonists and medullary thyroid cancer, particularly in rodents 6, 7.
• However, clinical evidence from randomized trials and observational studies suggests that thyroid cancer is a rare event, and there is no conclusive evidence of an increased risk in patients receiving GLP-1 receptor agonists 7.
• The use of GLP-1 receptor agonists in patients with a family history of medullary thyroid cancer should be approached with caution, and the potential benefits and risks of therapy should be carefully weighed 6, 7.

Considerations for Patients with a History of Gallstone Pancreatitis

• Patients with a history of gallstone pancreatitis may be at increased risk of recurrent pancreatitis, and the use of GLP-1 receptor agonists should be carefully considered in these patients 4, 5.
• However, some studies suggest that GLP-1 receptor agonists may not increase the risk of pancreatitis in patients with a history of pancreatitis of a known cause 3, 4.

Considerations for Patients with Stage Three CKD

• Patients with stage three CKD may benefit from the use of GLP-1 receptor agonists, which have been shown to reduce the risk of major cardiovascular disease and admission to hospital for heart failure 3.
• However, the use of GLP-1 receptor agonists in patients with CKD should be carefully monitored, as these agents may affect renal function 3.