SAN DIEGO – Recombinant human hyaluronidase combined with human regular insulin produced comparable glycemic responses to lispro insulin in a randomized open-label crossover study of 46 patients with well-controlled type 1 diabetes.
Recombinant human hyaluronidase (rHuPH20) is approved by the Food and Drug Administration to increase the dispersion and absorption of other injected drugs. This study investigated whether a combination of rHuPH20 with human regular insulin (Halozyme Therapeutics’ investigational Insulin-PH20) could produce glycemic control comparable to that of the currently available rapid-acting analogues. The ultimate aim is to combine it with those to make an even faster-acting analogue, Dr. Satish K. Garg said on June 25 at the annual scientific sessions of the American Diabetes Association.
“If we really want to achieve euglycemia in the postprandial phase, especially 1 and 2 hours after meals, we need an ultra–fast-acting insulin, and we don’t have that. So now, studies are on their way to look at using hyaluronidase with insulin lispro or another rapid-acting analogue to see if we can make it ultra–fast-acting insulin,” said Dr. Garg, professor of medicine and pediatrics at the University of Colorado, Denver.
The 46 patients had a mean age of 42 years, a mean body mass index of 26 kg/m2, and a mean hemoglobin A1c of 6.9%. They were randomized to either the Insulin-PH20 or insulin lispro for 2 consecutive 12-week periods, with twice-daily glargine as basal insulin in both groups. Forty-one of the 46 completed the trial.
The prespecified primary end point was a noninferiority margin of post-prandial glucose values not exceeding 21.6 mg/dL for three meals over 3 days. The difference in glycemic excursions between the two insulin formulations was 2.4 mg/dL, clearly meeting the end point, Dr. Garg said.
HbA1c was maintained for both groups in the trial, 7.0% for Insulin-PH20 and 6.9% for lispro, meeting the commonly applied noninferiority margin of 0.4%. Continuous glucose monitoring during the last 2 weeks of each treatment period showed similar mean glucose values (153 vs. 143 mg/dL), with similar amounts of time spent in the target range of 70-130 mg/dL (39% vs. 44%).
Overall hypoglycemia, defined as blood glucose value of 70 mg/dL or below, was 24.1 vs. 22.4 events per patient-month for Insulin-PH20 and lispro, respectively, a nonsignificant difference. There were no significant changes in anti-insulin and anti-lispro antibodies, Dr. Garg noted.
Studies are now investigating the combination of rHuPH20 and currently available rapid-acting analogues in type 1 and type 2 diabetes patients to see whether the course of action can be accelerated further.
Dr. Garg disclosed that he has received grants and honoraria from Halozyme Therapeutics, Sanofi-Aventis, Novo-Nordisk, Dexcom, and Eli Lilly.