Case Reports
Monday, October 14, 2024
01:00 PM–02:30 PM
Abstract
Introduction: Tirzepatide, a glucose-dependent insulinotropic polypeptide(GIP)/glucagon-like peptide (GLP-1) receptor agonist, increases insulin secretion in response to nutrients and reduces circulating glucagon. Although low rates (=1%) of severe hypoglycemia have been reported in clinical trials of tirzepatide, GLP has been associated with increased beta cell proliferation and non-insulinoma pancreatogenous hypoglycemia. This is the first reported case of severe hypoglycemia secondary to beta cell hyperplasia in the setting of tirzepatide use.
Case: A 58-year-old female with a past medical history of type 2 diabetes mellitus presented with severe hypoglycemia of 24 mg/dL. Home medications of metformin, tirzepatide, and insulin degludec were held, and a dextrose 10% infusion was initiated. Despite high infusion rates and continuous enteral nutrition, she remained intermittently hypoglycemic, with blood glucose levels reaching 52 mg/dL. Endocrinology was consulted. Insulin, beta-hydroxybutyrate, and C-peptide levels were inappropriate during confirmed hypoglycemic episodes, prompting consideration of an insulinoma. Imaging was negative for a pancreatic tumor, leading to the diagnosis of insulin-mediated hypoglycemia secondary to beta-cell hyperplasia. She was initiated on diazoxide on hospital day 23, with resolution of her hypoglycemia upon titration to 15 mg/kg/day, and was discharged on hospital day 30.
Discussion: Our patient’s severe and prolonged hypoglycemia was possibly associated with tirzepatide (Naranjo Scale 3). Non-insulinoma pancreatogenous hypoglycemia is characterized by insulin hypersecretion and subsequent hypoglycemia in the absence of an insulinoma. While rare, most cases are thought to be secondary to GLP-1-induced pancreatic cell hyperplasia occurring after bariatric surgery. Although beta cell hyperplasia has not been directly linked with incretin-based therapies, exenatide has been associated with a possible increased risk of pancreatic neuroendocrine tumors. Long term adverse effects of GLP-1 and GIP receptor agonists are not fully known.
Conclusion: Incretin-based therapies, particularly tirzepatide, may be associated with beta cell hyperplasia and insulin hypersecretion. Severe hypoglycemia risks should be considered for these agents.
Presenting Author
Erica Anderson PharmDAtrium Health Wake Forest Baptist Medical Center
Authors
Jon Doyle MD
Wake Forest University School of Medicine
Adrianna Elashker BA
Wake Forest University School of Medicine
Jacqueline Lippert MD, FACP
Atrium Health Wake Forest Baptist
Alexandra Mihm PharmD
Wingate University