By Wayne Kuznar
CHICAGO—Interim data from 2 ongoing clinical trials suggest that use of inhaled insulin (Exubera) as part of a basal-bolus insulin regimen leads to only a small decline in pulmonary function, an effect that is not progressive and is reversible upon discontinuation, said investigators at the American Diabetes Association annual meeting.
Furthermore, the use of inhaled insulin in combination with long- or intermediate-acting insulin achieves long-term levels of sustained glycemic control in patients with type 2 diabetes similar to those with subcutaneous insulin.
One of the studies has enrolled 627 patients with type 2 diabetes who were using multiple insulin injections at baseline. They were randomized to inhaled insulin or continued injected insulin for 2 years. Patients were then washed out for 6 months before being switched back to injected insulin. They were then re-administered their original randomized therapy for 6 more months.
The inhaled insulin group showed an early, small (mean, <0.1 L) reduction in forced expiratory volume in 1 second (FEV1) compared with the group that continued on subcutaneous insulin. The difference in FEV1 between the 2 groups resolved within 1 month of discontinuation of inhaled insulin. Upon reinstitution of inhaled insulin, the drop in FEV1was of the same magnitude as the initial decline.
"The pattern of change is consistent with a physiologic, not pathologic, effect of inhaled insulin on lung function," said William T. Cefalu, MD, lead investigator and chief, Division of Nutrition and Chronic Diseases, Louisiana State University, Baton Rouge.
Baseline hemoglobin A1c levels were 7.7% in both groups. After 3 years, patients in both groups had an A1c of approximately 7.4%. "Cessation and resumption of inhaled insulin therapy does not have any detrimental impact on its long-term efficacy," he said.
The patients randomized to inhaled insulin gained less weight (3.5 vs 6.4 lb) over the 3-year period than those assigned to subcutaneous insulin. Overall hypoglycemic and severe hypoglycemic event rates were similar between the groups.
Cough and shortness of breath were more common in the inhaled insulin group. The cough was mostly mild, started shortly after initiation, decreased over time, and rarely resulted in discontinuation, said Dr Cefalu.
A study with the same methodology is being conducted in 580 patients with type 1 diabetes. Interim results show the same small, nonprogressive decline in FEV1 in the inhaled insulin group, a decline that occurred early. As in the patients with type 2 diabetes, the differences in FEV1 between the groups resolved upon discontinuation of inhaled insulin, and recurred to the same magnitude during a 6-month extension phase of the study, reported Priscilla Hollander, MD, PhD, medical director of Baylor University Medical Center, Dallas.
Both treatment groups maintained glycemic control, said Dr Hollander, and the hypoglycemic event rates were similar.
Dr Cefalu recommends performing a spirogram before prescribing inhaled insulin to ensure adequate pulmonary function. He also advises that patients who quit smoking wait for approximately 6 months before using this agent.
Inhaled insulin may overcome some of the barriers to startinginsulin in patients with type 2 diabetes, one being fear of injections, said Lawrence Blonde, MD, director, Ochsner Diabetes Clinical Research Unit, New Orleans.
Patients with type 2 diabetesalso cite the demands of multiple insulin injections as another reason for eschewing insulin therapy, he said.