An open, randomized, parallel-group study to compare the efficacy and safety profile of inhaled human insulin (Exubera) with glibenclamide as adjunctive therapy in patients with type 2 diabetes poorly controlled on metformin.
OBJECTIVE
To compare the efficacy and safety profile of adding inhaled human insulin (INH) (Exubera) or glibenclamide to metformin monotherapy in patients with poorly controlled type 2 diabetes.


METHODS
We conducted an open-label, parallel, 24-week multicenter trial. Patients uncontrolled on metformin were randomized to adjunctive INH (n = 243) or glibenclamide (n = 233). Before randomization, patients were divided into two HbA(1c) (A1C) arms: > or =8 to < or =9.5% (moderately high) and >9.5 to < or =12% (very high). The primary efficacy end point was A1C change from baseline.


RESULTS
Mean adjusted A1C changes from baseline were -2.03 and -1.88% in the INH and glibenclamide groups, respectively; between-treatment difference -0.17% (95% CI -0.34 to 0.01; P = 0.058), consistent with the noninferiority criterion. In the A1C >9.5% arm, inhaled insulin demonstrated a significantly greater reduction in A1C than glibenclamide, between-treatment difference -0.37% (-0.62 to -0.12; P = 0.004). In the A1C < or =9.5% arm, between-treatment difference was 0.04% (-0.19 to 0.27; P = 0.733). Hypoglycemia (events per subject-month) was greater with INH (0.18) than glibenclamide (0.08), risk ratio 2.24 (1.58-3.16), but there were no associated discontinuations. Other adverse events, except increased cough in the INH group, were similar. At week 24, changes from baseline in pulmonary function parameters were small. Insulin antibody binding increased more with INH but did not have any associated clinical manifestations.


CONCLUSIONS
In patients with type 2 diabetes poorly controlled on metformin, adding INH or glibenclamide was similarly effective in improving glycemic control, and both were well tolerated. A predefined subgroup with very high A1C (>9.5%) was more effectively treated with the addition of INH.
Barnett
Anthony H
AH
University of Birmingham and Heart of England National Health Service Foundation Trust (Teaching), UK. anthony.barnett@heartofengland.nhs.uk
Dreyer
Manfred
M
Lange
Peter
P
Serdarevic-Pehar
Marjana
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000473:pathology; D004359:Drug Therapy, Combination; D005260:Female; D005905:Glyburide / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007328:Insulin / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D016896:Treatment Outcome
C473734:Exubera; D007328:Insulin; D008687:Metformin; D005905:Glyburide