Comparative Pharmacokinetics and Insulin Action for Three Rapid-Acting Insulin Analogs Injected Subcutaneously With and Without Hyaluronidase

  1. Daniel E. Vaughn, PHD2
  1. 1Profil Institute for Clinical Research, Chula Vista, California
  2. 2Halozyme Therapeutics Inc, San Diego, California
  1. Corresponding author: Daniel E. Vaughn, dvaughn{at}


OBJECTIVE To compare the pharmacokinetics and glucodynamics of three rapid-acting insulin analogs (aspart, glulisine, and lispro) injected subcutaneously with or without recombinant human hyaluronidase (rHuPH20).

RESEARCH DESIGN AND METHODS This double-blind six-way crossover euglycemic-glucose-clamp study was conducted in 14 healthy volunteers. Each analog was injected subcutaneously (0.15 units/kg) with or without rHuPH20.

RESULTS The commercial formulations had comparable insulin time-exposure and time-action profiles as follows: 50% exposure at 123–131 min and 50% total glucose infused at 183–186 min. With rHuPH20, the analogs had faster yet still comparable profiles: 50% exposure at 71–79 min and 50% glucose infused at 127–140 min. The accelerated absorption with rHuPH20 led to twice the exposure in the first hour and half the exposure beyond 2 h, which resulted in 13- to 25-min faster onset and 40- to 49-min shorter mean duration of insulin action.

CONCLUSIONS Coinjection of rHuPH20 with rapid-acting analogs accelerated insulin exposure, producing an ultra-rapid time-action profile with a faster onset and shorter duration of insulin action.

  • Received April 26, 2012.
  • Accepted July 31, 2012.

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  1. Diabetes Care
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