SUN-540 Glycemic Instability Associated With Gamma Secretase Inhibitor Therapy In A Type 1 Diabetic Patient Undergoing Treatment For Desmoid Tumor: A Case Report

Abstract Disclosure: J.C. Ramos Cardona: None. R. Morecroft-Phillipps: None. Introduction: Gamma secretase inhibitors (GSIs) are currently being investigated for use in desmoid tumortherapy. This therapy targets the Notch pathway which is associated with this tumor’spathogenesis can affect tumor growth, glucose metabolism and insulin sensitivity. Current dataon this association is limited and has only been described in vitro and in vivo mouse studies.Phase 3 of the DeFi trial (N=69), demonstrates glycosuria in approximately 5 participants butdata on adverse effects are not currently available for the phase 2 RINGSIDE trial. This caseuniquely describes GSI associated glycemic instability in a type 1 diabetic patient enrolled in theRINGSIDE trial for treatment of a left breast desmoid tumor. Case Description: A 31-year-old female with previously well controlled Type 1 Diabetes Mellitus and left breastdesmoid tumor presented with new onset glycemic instability after enrollment in a clinical trialinvolving a gamma secretase inhibitor. While on therapy, her clinical course was complicated byfluctuating glycemic control with recurrent diabetic ketoacidosis and hypoglycemic episodesrequiring frequent adjustments to her insulin therapy. Her glycemic control stabilized after beingdisenrolled from the clinical trial. Conclusion: We present a real-world case describing the association of GSIs with glycemic instability. Priorstudies (in vitro or in vivo mice models) have demonstrated the role of the Notch pathway inglycemic control; however, the data is limited especially in the realm of clinical practice. It alsohighlights the complexities of managing glycemic control in diabetic patients undergoing GSItherapy and emphasizes the importance of close endocrine follow up as well as integrated,multidisciplinary care. Presentation: Sunday, July 13, 2025