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 receivedsubcutaneous 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.
RCT Entities:
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 humaninsulin (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: Eda Cengiz; Stuart A Weinzimer; Jennifer L Sherr; Eileen M Tichy; Lori Carria; Darryll Cappiello; Amy Steffen; William V Tamborlane Journal: Diabetes Technol Ther Date: 2013-12-24 Impact factor: 6.118
Authors: Sanna Rosengren; Samuel S Dychter; Marie A Printz; Lei Huang; Richard I Schiff; Hans-Peter Schwarz; John K McVey; Fred H Drake; Dan C Maneval; Don A Kennard; Gregory I Frost; Barry J Sugarman; Douglas B Muchmore Journal: AAPS J Date: 2015-05-13 Impact factor: 4.009
Authors: A K J Gradel; T Porsgaard; J Lykkesfeldt; T Seested; S Gram-Nielsen; N R Kristensen; H H F Refsgaard Journal: J Diabetes Res Date: 2018-07-04 Impact factor: 4.011
Authors: Linda Morrow; Douglas B Muchmore; Marcus Hompesch; Elizabeth A Ludington; Daniel E Vaughn Journal: Diabetes Care Date: 2012-10-05 Impact factor: 19.112