title: 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.
  
  
  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.
authors.affiliation: Profil Institute for Clinical Research, Chula Vista, California, USA.
authors.forename: Marcus
authors.initials: M
authors.lastname: Hompesch
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Muchmore
authors.forename: Linda
authors.initials: L
authors.lastname: Morrow
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Vaughn
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects*; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D007328:Insulin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D016037:Single-Blind Method; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007328:Insulin; D006821:Hyaluronoglucosaminidase