Long-term tolerability of inhaled human insulin (Exubera) in patients with poorly controlled type 2 diabetes.
OBJECTIVE
Inhaled human insulin (Exubera; EXU) has shown encouraging tolerability in short-term trials. We evaluated the safety profile of EXU after long-term exposure.


METHODS
In two, open-label, 2-year studies patients poorly controlled on a sulphonylurea were randomised to adjunctive EXU or metformin (study 1) and patients poorly controlled on metformin were randomised to adjunctive EXU or the sulphonylurea, glibenclamide (study 2).


METHODS
The studies included 446 (study 1) and 476 (study 2) patients with type 2 diabetes, no clinically significant respiratory disease and glycosylated haemoglobin (HbA(1c)) levels of 8-12%.


METHODS
Main outcome measures were pulmonary function tests and insulin antibody assays.


RESULTS
A total of 109 patients (study 1) and 195 patients (study 2) completed 104 weeks treatment. In both studies, small treatment group differences in change from baseline forced expiratory volume in 1 s were greatest at 6 months (first time-point measured) and less at later visits, and reversed on treatment discontinuation. At 2 years, differences in mean changes were -0.10 and -0.01 l in studies 1 and 2, respectively, and -0.04 l for the pooled studies. There was no discernable effect of long-term EXU therapy on pulmonary gas exchange. Insulin antibody binding reached a plateau at 6 months and did not correlate with HbA(1c) or lung function changes. Glycaemic control was maintained over 2 years.


CONCLUSIONS
Exubera was well tolerated during long-term use. Pulmonary function changes compared with comparator groups were small, non-progressive and reversed upon treatment discontinuation. Importantly, rates of lung function change were indistinguishable between EXU and comparator after 6 months of therapy.
Barnett
A H
AH
University of Birmingham and Heart of England National Health Service Foundation Trust (Teaching), Birmingham, UK. anthony.barnett@heartofengland.nhs.uk
Lange
P
P
Dreyer
M
M
Serdarevic-Pehar
M
M
D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D016896:Treatment Outcome
D001786:Blood Glucose; C473734:Exubera; D007004:Hypoglycemic Agents; D007328:Insulin