A51-26 Refractory Hypoglycemia With Acute Renal Failure in Setting of Tripeptide and Sulphonyl Urea Use

Introduction Therapies like tirzepatide are increasingly being used for the management of type 2 diabetes mellitus (T2DM) and obesity. Despite their efficacy, some patients remain on oral sulfonylureas for additional glycemic control. When combined, these agents may significantly increase the risk of prolonged hypoglycemia, especially in the setting of acute kidney injury (AKI) due to reduced clearance. We present a case of refractory hypoglycemia for more than 4 days requiring octreotide in a patient on tirzepatide and glipizide who developed severe renal failure. Case Presentation A 70-year-old woman with T2DM, HFpEF, and prior DVT/PE presented with altered mental status and a blood glucose of 33 mg/dL. Home medications included spironolactone, torsemide, metformin, tirzepatide, glipizide, cephalexin, ciprofloxacin, and warfarin. She had recently been treated for a UTI and reported poor oral intake due to dysphagia. On arrival, vitals were BP 98/56, HR 80, RR 16, and SpO2 98%. Laboratory testing revealed creatinine 5.6 mg/dL (baseline 1.0), BUN 36, CO2 20, lactate 4.2, and pH 7.28; urinalysis showed trace ketones and proteinuria. Despite intravenous dextrose and glucagon, she continued to experience glucose readings <20 mg/dL and recurrent mental status changes. Given the combination of sulfonylurea use and AKI, octreotide was initiated. Following octreotide administration, her glucose stabilized in the 120s, and lactate normalized over 48 hours. However, her anuric AKI worsened (creatinine peaked at 8.0), and after initial improvement, she again developed hypoglycemia requiring repeat octreotide and D50 boluses. A subsequent bumetanide diuretic challenge successfully restored urine output, and her renal function gradually improved. Conclusion This case highlights an uncommon presentation of refractory and recurrent hypoglycemia due to glipizide and tirzepatide in the setting of severe renal failure. The persistence of hypoglycemia despite standard therapy highlights the prolonged half-life of these agents, especially with renal failure. The patient’s poor nutritional intake likely depleted hepatic glycogen stores, worsening hypoglycemia. Clinicians should maintain a high index of clinical suspicion for these patients with renal dysfunction on multiple drug regimens. Prompt initiation of octreotide helps, but ongoing monitoring is needed as hypoglycemia can recur until both renal function and nutritional status have improved. This abstract is funded by: Geisinger