title: Improved postprandial glycemic control in patients with type 2 diabetes from subcutaneous injection of insulin lispro with hyaluronidase.
abstract: BACKGROUND
  Coinjection of hyaluronidase has been shown to accelerate insulin absorption in healthy volunteers and patients with type 1 diabetes mellitus. This study was undertaken to compare the postprandial glycemic response of patients with type 2 diabetes mellitus (T2DM) administered insulin lispro with and without recombinant human hyaluronidase (rHuPH20) and regular human insulin (RHI) with rHuPH20.
  
  
  METHODS
  This double-blind three-way crossover study compared the insulin pharmacokinetics and glucodynamic response to a standardized liquid meal (80 g of carbohydrate) in 21 patients with T2DM who received subcutaneous injections of individually optimized doses of lispro±rHuPH20 and RHI+rHuPH20. The optimum dose (targeting postprandial glucose [PPG] of 70-140 mg/dL) of each preparation was selected by the investigator following a fixed-dose escalation procedure in three dose-finding meals.
  
  
  RESULTS
  Co-injection of lispro+rHuPH20 accelerated pharmacokinetics relative to lispro alone (time to peak insulin concentration, 43 vs. 74 min; P=0.0045) with increased exposure in the first hour (184% of control; P<0.0001) and reduced exposure after 2 h (67% of control; P=0.0001). These accelerated pharmacokinetics improved both total hyperglycemic excursions (area under the curve for 0-4 h >140 mg/dL, 56% of control; P=0.048) and hypoglycemic excursions (area under the curve for 0-8 h <70 mg/dL, 34% of control; P=0.033), allowing over three times as many patients to reach the American Diabetes Association's target of peak PPG <180 mg/dL without requiring glucose treatment for hypoglycemia. The mean optimum dose of lispro was reduced 8% from 0.275 U/kg without rHuPH20 to 0.254 U/kg with rHuPH20 (P=0.04). RHI+rHuPH20 had responses and optimum doses comparable to insulin lispro alone. All insulin preparations were well tolerated.
  
  
  CONCLUSIONS
  Lispro+rHuPH20 provided superior control of glycemic excursion compared with lispro alone, with lower insulin requirements and reduced hypoglycemic excursions.
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: Elizabeth
authors.initials: E
authors.lastname: Ludington
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; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007279:Injections, Subcutaneous; D061268:Insulin Lispro / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D061386:Insulin, Regular, Human / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D061268:Insulin Lispro; D061386:Insulin, Regular, Human; D006821:Hyaluronoglucosaminidase