Efficacy, tolerability of inhaled insulin sustained over two years

Pulmonary changes with inhaled insulin were small, occurred early and did not progress.

Issue: December 2006

Two-year interim data show that inhaled human insulin is well tolerated and offers glycemic control comparable to subcutaneous insulin.

“The study further supports previous findings that inhaled human insulin is an appropriate treatment for patients with type 1 diabetes,” said Jay S. Skyler, MD, professor of medicine, pediatrics and psychology and associate director of the Diabetes Research Institute at the University of Miami.

Skyler presented these findings at the 42nd European Association for the Study of Diabetes Annual Meeting held in Copenhagen.

For their study on inhaled human insulin (Exubera, Pfizer), Skyler and colleagues assessed pulmonary function using forced expiratory volume in 1 second [FEV1] and carbon monoxide diffusing capacity. They also collected efficacy data, including HbA1c, fasting plasma glucose, hypoglycemia and body weight.

The open-label, parallel group, multicenter study included 582 patients. Adults with type 1 diabetes who were on stable subcutaneous insulin with an HbA1c in the range of 5.5% to 11% at screening were included. A BMI less than 30 was also required for inclusion.

Patients who smoked within the last six months, had a history of active lung disease or whose pulmonary function tests at screening were at less than 70% of the predictive value for age and sex were excluded.

Small, early changes

The treatment differences in FEV1 and carbon monoxide diffusing capacity “were small – less than 1% and less than 2% of mean baseline values, respectively – they occurred early and they did not progress,” Skyler said.

Initially, HbA1c dropped and then gradually rose until there was no significant difference between the two insulin groups, Skyler said. The change in HbA1c from baseline to 24 months was a 0.1% increase for inhaled human insulin and a 0.2% decrease for subcutaneous insulin, according to an abstract of Skylr’s presentation.

FPG decreased more in the inhaled insulin group (from 171 mg/dL to 156.6 mg/dL) vs. the subcutaneous insulin group (from 167.4 mg/dL to 172.8 mg/dL).

With regard to overall hypoglycemia, the researchers found no differences between the two groups (four vs. 3.8 events/subject–month). However, there was less severe hypoglycemia in the inhaled insulin group (2.8 events/100 subject–month) compared with the subcutaneous group (4.1 events/100 subject–month). This contradicted a six-month study Skyler and colleagues presented last year with a different cohort, he said.

Weight gain was different between the groups. Although patients in the subcutaneous group gained nearly 2 kg, those in the inhaled human insulin group gained only 0.7 kg, he said.

Insulin antibody levels rose

Insulin antibody levels steadily increased by nine to 12 months and then dropped in the second year, which could not be explained, Skyler said. Insulin antibody levels did not progress, reversed upon discontinuation and were unrelated to pulmonary function. “There was no correlation with insulin antibody levels with any of the glucose control parameters, insulin doses or pharmacodynamics,” Skyler said.

Dosing of the inhaled insulin group increased over time, although the reason was not clear, Skyler said. “Subsequent analysis will try to analyze this by site to see if sites less experienced in the use of inhaled human insulin were perhaps more hesitant to use the full dose at the outset.”

Thirty-eight percent of patients in the inhaled insulin group developed a mild cough that was associated with dosing. A cough developed in 13.4% of patients in the subcutaneous group.

Dr. Skyler is a paid consultant for Pfizer.

For more information:

Skyler J, Jovanovic J, Klioze S, et al. Sustained efficacy and tolerability of inhaled human insulin therapy over two years: patients with type 1diabetes. Presented at: the 42nd European Association for the Study of Diabetes; Sept. 14-17, 2006; Copenhagen, Denmark.