Accelerating and improving the consistency of rapid-acting analog insulin
absorption and action for both subcutaneous injection and continuous subcutaneous
infusion using recombinant human hyaluronidase.
Author(s): Muchmore DB, Vaughn DE.
Affiliation(s): Halozyme Therapeutics Inc., San Diego, California 92121, USA.
dmuchmore@halozyme.com
Publication date & source: 2012, J Diabetes Sci Technol. , 6(4):764-72
Rapid-acting insulin analogs were introduced to the market in the 1990s, and
these products have improved treatment of diabetes by shortening the optimum
delay time between injections and meals. Compared with regular human insulin,
rapid-acting insulin formulations also reduce postprandial glycemic excursions
while decreasing risk of hypoglycemia. However, the current prandial products are
not fast enough for optimum convenience or control. Recombinant human
hyaluronidase (rHuPH20) has been used to increase the dispersion and absorption
of other injected drugs, and in the case of prandial insulin analogs, it confers
both ultrafast absorption and action profiles. Animal toxicology studies have
demonstrated excellent tolerability of rHuPH20, and human studies, involving over
60,000 injections of prandial insulin + rHuPH20 to date, have similarly shown
excellent safety and tolerability. Studies using rapid-acting analog insulin with
rHuPH20 have included clinic-based pharmacokinetic and glucodynamic euglycemic
glucose clamp studies, test meal studies, and take-home treatment studies.
Administration methods have included subcutaneous injection of coformulations of
rapid-acting insulin + rHuPH20 as well as continuous subcutaneous infusion of
coformulations or use of pretreatment of newly inserted infusion sets with
rHuPH20 followed by standard continuous subcutaneous insulin infusion therapy.
These studies have demonstrated acceleration of insulin absorption and action
along with improvement in postprandial glycemic excursions and reduction in
hypoglycemia risks. Further, rHuPH20 reduces intrasubject variability of insulin
absorption and action and provides greater consistency in absorption and action
profiles over wear time of an infusion set. Further studies of rHuPH20 in the
take-home treatment setting are underway.
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