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Improved Postprandial Glycemic Control in Patients with Type 2 Diabetes from Subcutaneous Injection of Insulin Lispro with Hyaluronidase.
MedLine Citation:
PMID:  22136324     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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:
Marcus Hompesch; Douglas B Muchmore; Linda Morrow; Elizabeth Ludington; Daniel E Vaughn
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-2
Journal Detail:
Title:  Diabetes technology & therapeutics     Volume:  -     ISSN:  1557-8593     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100889084     Medline TA:  Diabetes Technol Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1 Profil Institute for Clinical Research , Chula Vista, California.
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