Use of recombinant human hyaluronidase to accelerate rapid insulin analogue absorption: experience with subcutaneous injection and continuous infusion

To discuss clinical studies in which recombinant human hyaluronidase (rHuPH20) was used to increase insulin dispersion and accelerate its absorption.

We reviewed 10 pertinent clinical studies, 8 of which had data available.

In 4 euglycemic clamp studies, coinjection of rHuPH20 consistently yielded acceleration of insulin absorption, providing twice the insulin exposure during the first hour, greater and earlier peak exposure, and half the exposure beyond 2 hours after injection. Insulin-action profiles were similarly accelerated, with a 15-minute faster onset of insulin action and a 45-minute shorter duration of action for each of the 3 commercial rapid-acting insulin analogues. Infusion aspart insulin formulated with rHuPH20 also accelerated insulin absorption and action over the infusion set life when delivered by insulin pump. Administration of rHuPH20 reduced the inconsistency of insulin absorption and action profiles attributable to 3 factors-lack of reproducibility after identical injections, differences across insulin dose ranges, and changes over infusion site life. The rHuPH20-facilitated ultrafast profile consistently reduced hyperglycemic excursions both in injections immediately preceding liquid test meals and in bolus infusions immediately before solid test meals. rHuPH20-facilitated insulin administration has been well tolerated, with safety and tolerability similar to those with the comparator insulin alone.

rHuPH20 accelerates insulin-action profiles to an extent comparable to the difference between rapid-acting insulin analogue profiles and those of regular insulin. Studies are currently under way to characterize the effect on diabetes management end points (including hemoglobin A1c, blood glucose, and rates of hyperglycemia) of insulin analogues coformulated with rHuPH20 for treatment of both type 1 and type 2 diabetes.