Accelerated insulin pharmacokinetics and improved postprandial glycemic control in patients with type 1 diabetes after coadministration of prandial insulins with hyaluronidase

Abstract

Objective: To compare the pharmacokinetics, pharmacodynamics, and safety of insulin lispro or regular human insulin (RHI) with or without recombinant human hyaluronidase (rHuPH20) administered before a standardized meal.

Research design and methods: In this four-way, crossover study, 22 patients with type 1 diabetes received injections of individually optimized doses of lispro or RHI with and without rHuPH20 before a liquid meal.

Results: With rHuPH20 coadministration, early insulin exposure (0-60 min) increased by 54% (P = 0.0011) for lispro and 206% (P < 0.0001) for RHI compared with the respective insulin alone. Peak blood glucose decreased 26 mg/dL for lispro (P = 0.002) and 24 mg/dL for RHI (P = 0.017), reducing hyperglycemic excursions (area under the curve for blood glucose >140 mg/dL) by 79% (P = 0.09) and 85% (P = 0.049), respectively. Rates of hypoglycemia were comparable for lispro with or without rHuPH20, whereas coadministration of RHI and rHuPH20 reduced hypoglycemia.

Conclusions: Lispro or RHI with rHuPH20 produced earlier and greater peak insulin concentrations and improved postprandial glycemic control.

Trial registration: ClinicalTrials.gov NCT00774800.

Figures

Figure 1

Coadministration of rHuPH20 with lispro (A) or RHI (B) accelerates insulin pharmacokinetics as assessed by serum insulin concentrations, which were assayed using a standard insulin radioimmunoassay (Millipore, St. Charles, MO) validated for both lispro and RHI, and improved postprandial glycemic response (C and D) to a standardized liquid test meal (12 oz standard-formula Ensure [Abbott Laboratories, Abbott Park, IL]; 60 g carbohydrates). Blood glucose levels were determined using a YSI STAT2300 glucose analyzer (YSI Incorporated, Yellow Springs, OH). Data shown are from efficacy-evaluable populations.