SUN-343 Is GLP-1 Receptor Agonist Contraindicated In MEN2A Syndrome Despite A Prophylactic Thyroidectomy?

Abstract Disclosure: L. Ponce Rosas: None. A. Al-Thunaibat: None. P.S. Sidhu: None. J. Martins Torrontegui: None. A. Abualnil: None. K. Sanu: None. C. Penaherrera: None. Introduction: Multiple Endocrine Neoplasia type 2A (MEN2A) syndrome is characterized by the presence of primary hyperparathyroidism, pheochromocytoma, and medullary thyroid cancer (MTC). MTC can often be cured through prophylactic thyroidectomy. Glucagon-like peptide-1 (GLP1) receptor agonists are widely used for the management of type 2 diabetes mellitus (T2DM). While these agents offer excellent glycemic control, studies in rodents have shown an increased incidence of MTC. However, responses in humans and rodents can vary, and current evidence does not support a complete contraindication of GLP-1 receptor agonists in patients with a history of MEN2A syndrome. Case report A 62-year-old man with T2DM had suboptimal glycemic control despite metformin therapy, with a hemoglobin A1C of 9.7%. A GLP-1 receptor agonist, dulaglutide (4.5 mg weekly), was initiated to improve glycemic control, aiming for an A1C below 7%. The medication was well tolerated, and the patient remained adherent for two years. Subsequently, a family and personal history of MEN2A syndrome was identified and confirmed via genetic testing. Following the diagnosis, he underwent a prophylactic total thyroidectomy, which showed no evidence of MTC. His diabetes regimen at that time included dulaglutide and recently initiated sitagliptin 100 mg daily. Calcitonin levels remained undetectable. Although the decision was initially made to continue dulaglutide, insurance coverage was discontinued due to the MEN2A history. The current regimen includes 22 units of long-acting insulin at bedtime and sitagliptin 100 mg daily. The most recent A1C was 7.8%. Insulin doses have been frequently adjusted over the past year in efforts to optimize glycemic control after discontinuing the GLP-1 receptor agonist. Initially, the patient was hesitant to start insulin therapy due to concerns about daily injections, weight gain, and hypoglycemia risk. Discussion This case highlights the need for additional studies to determine the safety of long-term use of GLP-1 receptor agonists in patients with a history of medullary thyroid cancer who may benefit from these drugs. GLP-1 receptor agonists offer excellent glycemic control with a low risk of hypoglycemia and potential weight loss. They also reduce the risk of major cardiovascular events and help slow the progression of chronic kidney disease. Additionally, GLP-1 receptor agonists are often considered to have better compliance and adherence rates than insulin, especially in the long term. Conclusion There are not enough studies to determine the increased risk or recurrence of hereditary Medullary Thyroid Cancer on long-term use of Dulaglutide therapy, particularly in patients with MEN2A syndrome who have undergone prophylactic thyroidectomy, have negative pathology results, and consistently undetectable tumor markers such as calcitonin during annual follow-up. Presentation: Sunday, July 13, 2025