Randomized study to characterize glycemic control and short-term pulmonary function in patients with type 1 diabetes receiving inhaled human insulin (exubera).
OBJECTIVE
Previous studies with inhaled human insulin [Exubera (EXU); insulin human (recombinant DNA origin) Inhalation Powder, Pfizer Inc., New York, NY; Nektar Therapeutics, San Carlos, CA) show comparable efficacy to sc insulin and small declines in pulmonary function in type 1 and 2 diabetes. This is a detailed characterization of short-term efficacy and pulmonary safety profile of EXU.


METHODS
In a 24-wk multicenter study, 226 nonsmoking patients with type 1 diabetes and normal lung function were randomized to intensive regimens of premeal EXU or sc insulin for 12 wk (comparative phase), followed by sc insulin for 12 wk (washout phase). Glycosylated hemoglobin, hypoglycemia, general adverse events, and pulmonary function were measured. Forced expiratory volume in 1 sec and carbon monoxide diffusion capacity were measured using standardized equipment and methodology.


RESULTS
Comparable declines from baseline in glycosylated hemoglobin were observed in both groups (0.5%) and sustained throughout the study. There was a higher rate of hypoglycemia (risk ratio 1.23; 90% confidence interval 1.16, 1.30) but a lower rate of severe hypoglycemia (risk ratio 0.51; 90% confidence interval 0.30, 0.86) with EXU vs. sc insulin. The treatment group differences in changes from baseline in forced expiratory volume in 1 sec and carbon monoxide diffusion capacity were small, occurred within 2 wk of EXU initiation, and were reversible shortly after discontinuation. More patients reported mild cough with EXU vs. sc insulin (30.9% vs. 7.8%, respectively).


CONCLUSIONS
Three months of EXU therapy is as effective and well tolerated as intensive sc insulin therapy. This study supports the role of EXU in type 1 diabetes.
Norwood
Paul
P
University of California at San Francisco, Valley Research, Fresno, Ca 93720, USA. norwood@pol.net
Dumas
Richard
R
Cefalu
William
W
Yale
Jean-Francois
JF
England
Richard
R
Riese
Richard
R
Teeter
John
J
D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D003371:Cough / Q000139:chemically induced; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000188:drug therapy*; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007328:Insulin / Q000008:administration & dosage* / Q000009:adverse effects; D008168:Lung / Q000187:drug effects* / Q000502:physiology; D008875:Middle Aged; D012129:Respiratory Function Tests; D016896:Treatment Outcome
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; C473734:Exubera