Pharmacokinetics and Pharmacodynamics of Human Regular U-500 Insulin (U-500R) Administered via Continuous Subcutaneous Insulin Infusion (CSII) vs. Subcutaneous Injection (SCI) in Adults with Type 2 Diabetes and High Insulin Requirements

Abstract

There have been no euglycemic clamp studies on U-500R in obese patients with type 2 diabetes mellitus (T2DM) and high insulin requirements. This open-label, randomized, 2-way crossover, euglycemic clamp study (NCT02588950) evaluated PK/PD of U-500R administered by CSII (using an investigational Omnipod® U-500 Insulin Management System) compared to SCI (using a U-100 syringe), in adults with T2DM requiring >150 U/day of insulin. Subjects (N=11, mean BMI: 39.6 kg/m2, mean A1C: 10.2%) each received a 100 U dose via CSII [primed with a 12-hour (hour) U-500R basal infusion] and a single SCI, both followed by a 24 hour clamp. Serum insulin concentrations were corrected for endogenous insulin using C-peptide for both administration methods. Basal infusion values in CSII were adjusted with baseline and model corrections. Following SCI, using model corrected method, time of maximum observed drug concentration (tmax) was about 1.5 hour longer compared to CSII [LSmean ratio (90% CI): 1.46 (1.08, 1.97)]. There was no statistically significant difference between CSII and SCI in median tmax, areas under the curve [AUC(0-24), AUC(0-tlast)], and maximum concentration. There was no statistically significant difference between CSII and SCI in median time to maximum glucose infusion rate (GIR) [CSII: 7.2 hour; SCI: 8 hour], median time of 50% of maximum GIR before Rmax (tRmax50) [CSII: 2.85 hour; SCI: 3.59 hour], and median time to last GIR [CSII: 18.9 hour; SCI: 14.6 hour]. No severe hypoglycemia was reported. U-500R was well tolerated whether given by syringe or CSII. The PK/PD profiles and time action parameters were similar with both methods of administration. Disclosure X. Ma: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. R.P. Prescilla: None. S. Zhang: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Spouse/Partner; Eli Lilly and Company. H. Linnebjerg: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. L. Morrow: Stock/Shareholder; Self; ProSciento. Employee; Spouse/Partner; Eli Lilly and Company. J.A. Jackson: Other Relationship; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. J. Johnson: Employee; Self; Eli Lilly and Company. D. Leishman: Employee; Self; Eli Lilly and Company.