Subcutaneous injection of hyaluronidase with recombinant human insulin compared with insulin lispro in type 1 diabetes

Aims: Prandial treatment with human regular insulin for diabetes may result in early postprandial hyperglycaemia and late hypoglycaemia due to its slow onset and long duration of action. This study compared injections of recombinant human insulin (rHI) formulated with recombinant human hyaluronidase [rHuPH20] (INSULIN-PH20) to insulin lispro for prandial treatment in subjects with type 1 diabetes (T1D). Methods: After a 1-month run-in period using twice-daily insulin glargine (or usual basal insulin therapy for pump users) with prandial lispro, 46 subjects with T1D (42 +/- 13 years; body mass index: 26 +/- 4 kg/m(2); A1c: 6.8 +/- 0.5%) were assigned to INSULIN-PH20 or lispro in a random sequence for two consecutive, 12-week periods as the prandial insulin in an intensive treatment regimen. Results: The mean glycaemic excursion for INSULIN-PH20 (0.96 +/- 2.00 mmol/l) was comparable (p=0.322) to lispro (0.80 +/- 1.95 mmol/l). The 8-point self-monitored blood glucose profiles were also comparable in the two groups. Good glycaemic control (A1c) was maintained for both treatments at 12 weeks (INSULIN-PH20: 7.0 +/- 0.5%; lispro: 6.9 +/- 0.6%). Overall rates of hypoglycaemia (<= 3.9 mmol/l) were 24 events per patient per 4 weeks for INSULIN-PH20 and 22 events for lispro. There were no significant differences in adverse events or immunogenicity between treatments and both treatments were well tolerated. Conclusions: Unlike commercially available formulations of regular human insulin, a formulation of rHI with rHuPH20 was comparable to lispro for postprandial glucose excursions in a basal-bolus treatment regimen for T1D patients. Glycaemic control, safety and tolerability profiles were comparable for both treatments.