An Open, Randomized, Parallel-Group Study to Compare the Efficacy and Safety Profile of Inhaled Human Insulin (Exubera) With Metformin as Adjunctive Therapy in Patients With Type 2 Diabetes Poorly Controlled on a Sulfonylurea
- Anthony H. Barnett, BSC, MD, FRCP1,
- Manfred Dreyer, MD2,
- Peter Lange, MD3,
- Marjana Serdarevic-Pehar4 and
- on behalf of the Exubera Phase III Study Group
- 1University of Birmingham and Heart of England National Health Service Foundation Trust (Teaching), Birmingham, U.K.
- 2Department of Diabetes and Metabolism, Bethanien Krankenhaus, Hamburg, Germany
- 3Department of Respiratory Medicine, Hvidovre University Hospital, Hvidovre, Denmark
- 4Department of Respiratory Medicine, Pfizer, Sandwich, U.K.
- Address correspondence and reprint requests to A.H. Barnett, Undergraduate Centre, Birmingham Heartlands Hospital, Bordesley Green East, Birmingham, B9 5SS, UK. E-mail: anthony.barnett{at}heartofengland.nhs.uk
Abstract
OBJECTIVE—To compare the efficacy and safety profile of adding inhaled human insulin (INH; Exubera) or metformin to sulfonylurea monotherapy in patients with poorly controlled type 2 diabetes.
RESEARCH DESIGN AND METHODS—We performed an open-label, parallel, 24-week, multicenter trial. At week −1, patients uncontrolled on sulfonylurea monotherapy were divided into two HbA1c (A1C) arms: ≥8 to ≤9.5% (moderately high) and >9.5 to ≤12% (very high). Patients were randomized to adjunctive premeal INH (n = 225) or metformin (n = 202). The primary efficacy end point was change in A1C from baseline.
RESULTS—In the A1C >9.5% arm, INH demonstrated a significantly greater reduction in A1C than metformin. Mean adjusted changes from baseline were −2.17 and −1.79%, respectively; between-treatment difference was −0.38% (95% CI −0.63 to −0.14, P = 0.002). In the A1C ≤9.5% arm, mean adjusted A1C changes were −1.94 and −1.87%, respectively (−0.07% [−0.33 to 0.19], P = 0.610), consistent with the noninferiority criterion. Hypoglycemia (events/subject-month) was greater in the INH (0.33) than in the metformin (0.15) group (risk ratio 2.16 [95% CI 1.67–2.78]), but there were no associated discontinuations. Other adverse events, except increased cough in the INH group, were similar. At week 24, changes in pulmonary function parameters were small and comparable between groups. 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 a sulfonylurea (A1C >9.5%), the addition of premeal INH significantly improves glycemic control compared with adjunctive metformin and is well tolerated.
- ADA, American Diabetes Association
- DLco, carbon monoxide transfer factor
- FEV1, forced expiratory volume in 1 s
- INH, inhaled human insulin
Footnotes
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A.H.B. has received honoraria and research grants from Eli Lilly, Novo Nordisk, and Roche. M.D. has received honoraria from Sanofi-Aventis, Novo Nordisk, Eli Lilly, GlaxoSmithKline, and Astra Zeneca. P.L. is a member of an advisory panel for and receives consulting fees from Sanofi-Aventis.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement“ in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted February 17, 2006.
- Received October 4, 2005.
- DIABETES CARE
