Two-Year Pulmonary Safety and Efficacy of Inhaled Human Insulin (Exubera) in Adult Patients With Type 2 Diabetes

  1. Julio Rosenstock, MD1,
  2. William T. Cefalu, MD2,
  3. Priscilla A. Hollander, MD3,
  4. Andre Belanger, MD4,
  5. Freddy G. Eliaschewitz, MD5,
  6. Jorge L. Gross, MD6,
  7. Solomon S. Klioze, PHD7,
  8. Lisa B. St. Aubin, DVM, MPVM7,
  9. Howard Foyt, MD, PHD8,
  10. Masayo Ogawa, MD8 and
  11. William T. Duggan, PHD7
  1. 1Dallas Diabetes and Endocrine Center, Dallas, Texas
  2. 2Pennington Biomedical Research Center, Baton Rouge, Louisiana
  3. 3Baylor University Medical Center, Dallas, Texas
  4. 4Cité de la Santé Hospital, Laval, Quebec, Canada
  5. 5Hospital Albert Einstein, São Paulo, São Paulo, Brazil
  6. 6Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
  7. 7Pfizer Global Research and Development, New London, Connecticut
  8. 8Pfizer Global Research and Development, Ann Arbor, Michigan
  1. Corresponding author: Julio Rosenstock, juliorosenstock{at}dallasdiabetes.com

Abstract

OBJECTIVE—The purpose of this study was to evaluate the 2-year pulmonary safety of inhaled human insulin (Exubera [EXU]) in 635 nonsmoking adults with type 2 diabetes.

RESEARCH DESIGN AND METHODS—Patients were randomly assigned to receive prandial EXU or subcutaneous insulin (regular or short-acting) plus basal (intermediate- or long-acting) insulin. The primary end points were the annual rate of decline in forced expiratory volume in 1 s (FEV1) and carbon monoxide diffusing capacity (DLCO).

RESULTS—Small differences in FEV1 favoring subcutaneous insulin developed during the first 3 months but did not progress. Adjusted treatment group differences in FEV1 annual rate of change were −0.007 l/year (90% CI −0.021 to 0.006) between months 0 and 24 and 0.000 l/year (−0.016 to 0.016) during months 3–24. Treatment group differences in DLCO annual rate of change were not significant. Both groups sustained similar reductions in A1C by month 24 (last observation carried forward) (EXU 7.7–7.3% vs. subcutaneous insulin 7.8–7.3%). Reductions in fasting plasma glucose (FPG) were greater with EXU than with subcutaneous insulin (adjusted mean treatment difference −12.4 mg/dl [90% CI −19.7 to −5.0]). Incidence of hypoglycemia was comparable in both groups. Weight increased less with EXU than with subcutaneous insulin (−1.3 kg [−1.9 to −0.7]). Adverse events were comparable, except for a higher incidence of mild cough and dyspnea with EXU.

CONCLUSIONS—Two-year prandial EXU therapy showed a small nonprogressive difference in FEV1 and comparable sustained A1C improvement but lower FPG levels and less weight gain than seen in association with subcutaneous insulin in adults with type 2 diabetes.

Footnotes

  • Published ahead of print at http://care.diabetesjournals.org on 5 June 2008.

    Clinical trial reg. no. NCT00136916, clinicaltrials.gov.

    J.R. has served on advisory boards and received honoraria or consulting fees from Pfizer, sanofi aventis, Novo Nordisk, GlaxoSmithKline, Takeda, Centocor, Johnson & Johnson, and Amylin and has received grant support from Merck, Pfizer, sanofi aventis, Novo Nordisk, Eli Lilly, GlaxoSmithKline, Takeda, Novartis, AstraZeneca, Amylin, Sankyo, and MannKind. W.T.C. has served on advisory committees for Pfizer, Amylin, Eli Lilly, Merck, and Novartis and has received grant support from Pfizer, Amylin, Eli Lilly, Merck, and Novo Nordisk. P.A.H. has served on advisory boards and as a speaker for Pfizer, sanofi aventis, and Merck. A.B. is a member of the Canadian National Advisory Board for Exubera. F.G.E. has received consulting fees from Pfizer and sanofi aventis and is involved in sponsored clinical trials for Pfizer, sanofi aventis, Takeda, Novartis, and Novo Nordisk.

    The current status of Exubera, including the change in labeling regarding lung carcinoma, is summarized in the Pfizer Statement available in an online appendix (http://dx.doi.org/10.2337/dc08-0159).

    Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

    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.

    • Accepted May 30, 2008.
    • Received January 23, 2008.
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  1. Published online before print June 5, 2008, doi: 10.2337/dc08-0159 Diabetes Care September 2008 vol. 31 no. 9 1723-1728
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