MON-037 GLP-1 Receptor Agonists in MEN1-Associated Glucagonoma: Exploring Glycemic Control and Tumor Stability

Abstract Disclosure: R.R. Savian: None. C.V. Villabona: None. E. Bernal-Mizrachi: None. Background: Managing glucagonoma-associated diabetes in MEN1 is challenging due to hyperglucagonemia and severe hyperglycemia. GLP-1 receptor agonists (GLP-1RAs) suppress glucagon and improve glycemia in type 2 diabetes mellitus (T2DM), but their role in glucagonoma is poorly understood, with concerns about their effects on functional pancreatic neuroendocrine tumors (pNETs). Case Description: A 53-year-old male with MEN1 was diagnosed in 2009 after nephrolithiasis revealed pancreatic lesions. Subtotal pancreatectomy confirmed five glucagon-positive pNETs, the largest measuring 3 cm. Despite surgery, Cu-64 DOTATATE PET/CT in February 2024 revealed recurrent disease with a 1.9 cm pancreatic neck lesion (SUV 26.1) and a 1.3 cm peripancreatic lymph node (SUV 121.6). Baseline glucagon levels were 225 pg/mL (normal <50), reflecting significant tumor secretion.The patient began intermittent GLP-1RA therapy with semaglutide in 2019, transitioning to tirzepatide in early 2024. GLP-1RAs were discontinued in February 2024 due to safety concerns, leading to worsened glycemic control, with HbA1c increasing from 8.7% to 10.1%, CGM mean glucose rising to 223 mg/dL, and TIR decreasing to 20%. In June 2024, lanreotide 120 mg monthly was initiated, partially suppressing glucagon (65 pg/mL), but HbA1c remained elevated at 9.6%. Semaglutide was reintroduced in August 2024, starting at 1 mg weekly and titrated to 2 mg. By October 2024, glucagon normalized (<50 pg/mL), HbA1c improved to 8.2%, CGM mean glucose decreased to 204 mg/dL, and TIR increased to 31%.Follow-up Cu-64 DOTATATE PET/CT in December 2024 confirmed stable tumor size and metabolic activity: the pancreatic neck lesion remained 1.9 cm (SUV 14.9), and the peripancreatic lymph node remained 1.3 cm (SUV 107.2). Discussion: GLP-1 receptor agonists are contraindicated in MEN2 due to concerns about medullary thyroid carcinoma from preclinical data, but no such contraindications exist for MEN1. This case highlights the limited evidence for GLP-1RAs in glucagonoma and demonstrates their potential to improve glycemia without accelerating tumor growth and potentially suppressing it, as suggested by stable imaging and biochemical markers. However, overlapping effects of lanreotide and GLP-1RAs complicate isolation of their individual contributions. Conclusion: GLP-1 receptor agonists, combined with somatostatin analogs, may provide a safe and effective strategy for managing glucagonoma-associated diabetes in MEN1. Additional research is needed to assess their long-term safety and efficacy in functional pNETs. Presentation: Monday, July 14, 2025