PMID- 22136324
OWN - NLM
STAT- MEDLINE
DCOM- 20120614
LR  - 20220409
IS  - 1557-8593 (Electronic)
IS  - 1520-9156 (Linking)
VI  - 14
IP  - 3
DP  - 2012 Mar
TI  - Improved postprandial glycemic control in patients with type 2 diabetes from 
      subcutaneous injection of insulin lispro with hyaluronidase.
PG  - 218-24
LID - 10.1089/dia.2011.0117 [doi]
AB  - 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.
FAU - Hompesch, Marcus
AU  - Hompesch M
AD  - Profil Institute for Clinical Research, Chula Vista, California, USA.
FAU - Muchmore, Douglas B
AU  - Muchmore DB
FAU - Morrow, Linda
AU  - Morrow L
FAU - Ludington, Elizabeth
AU  - Ludington E
FAU - Vaughn, Daniel E
AU  - Vaughn DE
LA  - eng
SI  - ClinicalTrials.gov/NCT00916357
PT  - Clinical Trial, Phase II
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20111202
PL  - United States
TA  - Diabetes Technol Ther
JT  - Diabetes technology & therapeutics
JID - 100889084
RN  - 0 (Blood Glucose)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin Lispro)
RN  - 0 (Insulin, Regular, Human)
RN  - EC 3.2.1.35 (Hyaluronoglucosaminidase)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Blood Glucose/*drug effects
MH  - Cross-Over Studies
MH  - Diabetes Mellitus, Type 2/blood/*drug therapy/epidemiology
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Hyaluronoglucosaminidase/administration & dosage/blood/*pharmacokinetics
MH  - Hypoglycemic Agents/administration & dosage/blood/*pharmacokinetics
MH  - Injections, Subcutaneous
MH  - Insulin Lispro/administration & dosage/blood/*pharmacokinetics
MH  - Insulin, Regular, Human/administration & dosage/blood/*pharmacokinetics
MH  - Male
MH  - Middle Aged
MH  - Postprandial Period
MH  - Treatment Outcome
MH  - United States/epidemiology
MH  - Young Adult
EDAT- 2011/12/06 06:00
MHDA- 2012/06/15 06:00
CRDT- 2011/12/06 06:00
PHST- 2011/12/06 06:00 [entrez]
PHST- 2011/12/06 06:00 [pubmed]
PHST- 2012/06/15 06:00 [medline]
AID - 10.1089/dia.2011.0117 [doi]
PST - ppublish
SO  - Diabetes Technol Ther. 2012 Mar;14(3):218-24. doi: 10.1089/dia.2011.0117. Epub 
      2011 Dec 2.