THU380 A Case Of Alpelisib Induced Diabetic Ketoacidosis (Dka) In A Patient With Type 2 Diabetes Mellitus And Rechallenge With SGLT2 Inhibitor

Abstract

Abstract Disclosure: V. Sekar: None. S. Shaik: None. Introduction: Alpelisib is a α-selective phosphatidylinositol 3-kinase (PI3K) inhibitor recently used in treatment of advanced breast cancer. Hyperglycemia is an expected adverse effect with the use of PI3K inhibitors. We report a case of Alpelisib induced worsening hyperglycemia in a patient with type 2 diabetes mellitus who developed DKA while on Empagliflozin and was rechallenged with Dapagliflozin to achieve better glycemic control. Case Description: 60-year-old female with known history of type 2 diabetes mellitus was referred to Endocrinology prior to the start of PI3K inhibitor, Alpelisib for metastatic breast cancer. On initial visit her Hemoglobin A1C was 7.4 % and she was on Empagliflozin 25 mg daily, Sitagliptin 100 mg daily, Metformin XR 500 mg daily and Insulin Glargine 30 units daily. Three weeks after initiation of Alpelisib, patient reported uncontrolled fasting and post-prandial hyperglycemia, therefore her basal insulin was up-titrated and added on prandial insulin. Sitagliptin was discontinued. Two weeks later patient was admitted with Euglycemic diabetic ketoacidosis (DKA) which was treated with IV insulin and IV fluids. Empagliflozin was stopped and discharged on basal bolus regimen. In the next 6 weeks basal bolus regimen was significantly up-titrated and added on correctional insulin along with increasing Metformin XR to 500 mg twice a day due to poor glycemic control. During this time patient was cautiously restarted on Dapagliflozin 5 mg daily after discussing the better outcomes for Alpelisib induced hyperglycemia versus risk of DKA with reuse of SGLT2 inhibitors. Since being on Dapagliflozin her blood sugars were better controlled and the insulin requirements plateaued. Patient was closely monitored, and she didn’t develop further episode of DKA. Discussion: The PI3K pathway controls the effect of insulin intracellularly and its activation promotes tumor development, spread and failure to anticancer treatment. PI3K inhibitor blocks the intracellular action of insulin which causes reversible insulin resistance and hyperglycemia which is the major side effect of this drug. Use of insulin to treat hyperglycemia was shown to partially reactivate the PI3K pathway in tumoral cells, leading to cellular proliferation. Therefore, insulin should be kept as the last line antihyperglycemic agent. Exploratory analysis of SOLAR-1* trial has shown better glycemic control with use of SGLT2 inhibitors in patient with Alpelisib induced hyperglycemia along with improved efficacy of Alpelisib against tumor growth. Both PI3K inhibitor and SGLT2 inhibitor has risk of causing DKA, but close monitoring and patient education helps to reduce the risk. Reference *Study Assessing the Efficacy and Safety of Alpelisib Plus Fulvestrant in Men and Postmenopausal Women with Advanced Breast Cancer Which Progressed on or After Aromatase Inhibitor Treatment Presentation: Thursday, June 15, 2023