SUN-542 - Automated Insulin Delivery System with Concentrated Regular U500 Insulin in Chronic Kidney Disease

Background: Concentrated regular U-500 (U-500R) insulin is commonly used in patients with T2DM who are highly insulin-resistant. However, there is a concern of insulin-related hypoglycemia in patients with CKD due to decreased kidney clearance of insulin and gluconeogenesis, malnutrition leading to decreased glycogen stores, and impaired counterregulatory responses. We previously reported the safe and effective use of U-500R in an automated insulin delivery (AID) system, although without CKD (1). In the VIVID study, which compared U-500R administration via multiple daily injections to an investigational U-500R insulin pump, patients with CKD Stage 4+, were excluded, and there was an increase in nocturnal hypoglycemia for patients using an insulin pump (2). There is limited data to support the safe use of U-500R in AID systems for patients with CKD. We present 3 patients with CKD Stage G3b-4 who switched from U-100 rapid-acting insulin to U-500R in Omnipod 5 (OP5) AID.

Clinical

Case: Patient 1 is a 54 yo male with T2DM, CKD Stage G3b/A1, ASCVD, HF, and obesity with a baseline A1c 10.6%. Prior to his switch to U-500R, his glucometrics were: glucose management indicator (GMI) 9.1%, time-in-range (TIR) 16%, and insulin total daily dose (TDD) 172 units. 3 months later: GMI 7.2%, TIR 69%, and insulin TDD 37 “pump” units. Patient 2 is a 68 yo male with T2DM, CKD Stage G3b/A2, orthotopic heart transplant (OHT), and obesity with a baseline A1c 8.1%. Prior to his switch to U-500R, his glucometrics were: GMI 8.6%, TIR 22%, and insulin TDD 86 units. 3 months later: GMI 6.9%, TIR 81%, and insulin TDD 23 “pump” units. Patient 3 is a 60 yo female with T2DM, CKD Stage G4/A2, OHT, familial hypertriglyceridemia, and obesity with a baseline A1c 8.5%. Prior to her switch to U-500R, her glucometrics were: GMI 9.9%, TIR 16%, and insulin TDD 73 units. 3 months later: GMI 7.9%, TIR 46%, and insulin TDD 48 “pump” units. Each patient was switched from U-100 rapid-acting insulin to U-500R due to frequent hyperglycemia and high daily insulin doses resulting in frequent pod changes. No patients had symptoms suggestive of hypoglycemia and time-below-range was 0%. Patient 1 and 2 had a higher overnight BG target to reduce the risk of nocturnal hypoglycemia; Patient 3 had no changes in BG target.

Conclusion: Patients with CKD Stage G3b-4 using U-500R in OP5 AID proved to be safe and effective. Specifically, no patients developed hypoglycemia and no significant changes in glucose variability. Frequent touchpoints with a clinical pharmacist as part of the care team helped to optimize outcomes. Of note, these patients successfully switched from U-500R vials to pens with the discontinuation of vials late 2025. Further research will be required for patients with advanced CKD (Stage G4-5) and using U-500R in AID.

References:
1. Aurora J Jr, Saraswat A. J Endocr Soc. 2023;7(Suppl 1):bvad114.873.
2. Grunberger G, et al. Diabetes Obes Metab. 2020;22(3):434-441.

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