SAT-607 - The Role of GLP-1 Receptor Agonist Therapy in Resolving Severe Hypoglycemia and Achieving Insulin Independence in A Patient with Pancreoprivic Diabetes Following Total Pancreatectomy with Autologous Islet Cell Transplantation

Introduction

Total pancreatectomy with autologous islet cell transplantation (TPIAT) is the standard of care for patients with preserved islet cell function who experience severe chronic pancreatitis with intractable pain not responsive to maximal medical therapy. The main goal of islet cell auto transplantation is to prevent or ameliorate post-pancreatectomy diabetes (PPD), which can be challenging to manage, due to its brittle nature, prone to severe hypoglycemia. Use of Glucagon-like peptide -1 receptor agonist (GLP-1 RA) to treat PPD after TPIAT has been reported but not well characterized. We present a case of PPD with severe hypoglycemia after TPIAT that was successfully treated with GLP-1 RA.

Case Summary

The patient is a 32-year-old female with body mass index of 16 and genetic risk factors as carrier for multiple gene mutations for recurrent pancreatitis, pancreas divisum who first presented with acute pancreatitis at age 22. Despite initial procedural and medical treatment, the patient continued to experience frequent episodes of acute on chronic pancreatitis requiring 22 hospitalizations over the course of the next 7 years and developed mild narcotic dependence due to intractable pain. She underwent TPIAT at age 30, developed PPD afterwards and was managed with multiple daily insulin injections (around total daily dose of 15 units on average) and continuous glucose monitor (CGM). Course was complicated with some labile glucose and hypoglycemia resulting in an emergency room visit after a hypoglycemic seizure related to failed CGM alert 22 months after TPIAT. She was initiated on low dose Semaglutide weekly injections afterwards, with improvement of glycemia control, able to wean off insulin completely few months later. She tolerated Semaglutide well, is currently maintained on Semaglutide 0.5mg weekly, with resolution of hypoglycemia and insulin dependence so far, 9 months after.

Discussion

Patients following TPIAT may achieve insulin independence in about 25-40% of cases, with the percentage of insulin independence rising proportionally with a greater number of islet cell equivalents transplanted. GLP-1 RAs have been approved to treat Type 2 diabetes and obesity, reducing cardiovascular and chronic kidney disease risks. There is also ongoing investigation on the use of GLP-1 RA in the treatment of PPD after TPIAT. GLP-1 RA can support autologous islet cell function, improve postprandial hyperglycemia, and reduce hypoglycemia via enhancing glucose-dependent endogenous insulin secretion. Our case highlights GLP-1 RA could be beneficial in patients with PPD after TPIAT, as an adjunctive therapy. Prior pancreatitis is not an absolute contraindication post pancreatectomy, though gastrointestinal side effects, malnutrition, and weight loss could be of clinical concerns. More studies are needed to assess the long-term efficacy and safety of GLP-1 RA in patients after TPIAT.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*