Two-year safety and efficacy of inhaled human insulin (exubera) in adult patients with type 1 diabetes

Jay S Skyler, Lois Jovanovic, Sol Klioze, Joann Reis, William Duggan

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

OBJECTIVE - The purpose of this study was to evaluate the long-term (2-year) safety and efficacy of inhaled human insulin (Exubera [insulin human (rDNA origin)] inhalation powder) (EXU) in adult patients with type 1 diabetes. RESEARCH DESIGN AND METHODS - Patients were randomly assigned to receive EXU (n = 290) or subcutaneous (SC) insulin (n = 290), plus basal (intermediate- or long-acting) insulin. The primary end point was the annual rate of decline in pulmonary function (forced expiratory volume in 1 s [FEV1] and carbon monoxide diffusing capacity [DLCO]). RESULTS - The mean ± SEM annual rates of change between months 0 and 24 were -0.051 ± 0.005 l/year with EXU and -0.034 ± 0.005 l/year with SC insulin (significant mean difference -0.017 ± 0.007 l/year [90% CI -0.028 to -0.005]) for FEV1 and -0.437 ± 0.073 ml·min -1·mmHg-1·year-1 with EXU and -0.287 ± 0.065 ml·min-1·mmHg -1·year-1with SC insulin (nonsignificant mean difference -0.150 ml·min-1·mmHg -1·year-1 [-0.310 to 0.011]) for DLCO. The mean annual rates of change in FEV1 between months 3 and 24 were -0.041 ± 0.005 and -0.031 ± 0.006 l/year in the EXU and SC insulin groups, respectively (nonsignificant mean difference -0.011 l/year [-0.023 to 0.002]), indicating that the significant difference between the treatment groups in FEV1 developed during the first 3 months and was not progressive thereafter. Adverse event profiles were similar except for a higher incidence of cough (usually mild and unproductive) in patients receiving EXU (37.6 vs. 13.1%) that decreased to 1.3% by month 24. Glycemic control was sustained in both groups (adjusted mean treatment difference in change from baseline A1C at month 24 0.25 ± 0.07% [0.13-0.37]). Although the overall hypoglycemic events were comparable between groups (4.0 vs. 3.8 events/subject-month), the incidence of severe hypoglycemic events was lower with EXU than with SC insulin (2.8 vs. 4.1 events/100 subject-months, risk ratio 0.67 [0.57-0.79]). Body weight increased to a significantly lesser extent with EXU (adjusted mean treatment difference -1.25 ± 0.36 kg [-1.85 to -0.66]). CONCLUSIONS - Treatment group differences in lung function between EXU and SC insulin in adult patients with type 1 diabetes are small, develop early, and are nonprogressive for up to 2 years of therapy.

Original languageEnglish
Pages (from-to)579-585
Number of pages7
JournalDiabetes Care
Volume30
Issue number3
DOIs
StatePublished - Mar 1 2007

Fingerprint

Type 1 Diabetes Mellitus
Insulin
Safety
Forced Expiratory Volume
Hypoglycemic Agents
Long-Acting Insulin
Therapeutics
Lung
Exubera
Incidence
Carbon Monoxide
Ribosomal DNA
Cough
Powders
Inhalation
Research Design
Odds Ratio
Body Weight

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Two-year safety and efficacy of inhaled human insulin (exubera) in adult patients with type 1 diabetes. / Skyler, Jay S; Jovanovic, Lois; Klioze, Sol; Reis, Joann; Duggan, William.

In: Diabetes Care, Vol. 30, No. 3, 01.03.2007, p. 579-585.

Research output: Contribution to journalArticle

Skyler, Jay S ; Jovanovic, Lois ; Klioze, Sol ; Reis, Joann ; Duggan, William. / Two-year safety and efficacy of inhaled human insulin (exubera) in adult patients with type 1 diabetes. In: Diabetes Care. 2007 ; Vol. 30, No. 3. pp. 579-585.
@article{b76f76aabdee48b999fea7205248b377,
title = "Two-year safety and efficacy of inhaled human insulin (exubera) in adult patients with type 1 diabetes",
abstract = "OBJECTIVE - The purpose of this study was to evaluate the long-term (2-year) safety and efficacy of inhaled human insulin (Exubera [insulin human (rDNA origin)] inhalation powder) (EXU) in adult patients with type 1 diabetes. RESEARCH DESIGN AND METHODS - Patients were randomly assigned to receive EXU (n = 290) or subcutaneous (SC) insulin (n = 290), plus basal (intermediate- or long-acting) insulin. The primary end point was the annual rate of decline in pulmonary function (forced expiratory volume in 1 s [FEV1] and carbon monoxide diffusing capacity [DLCO]). RESULTS - The mean ± SEM annual rates of change between months 0 and 24 were -0.051 ± 0.005 l/year with EXU and -0.034 ± 0.005 l/year with SC insulin (significant mean difference -0.017 ± 0.007 l/year [90{\%} CI -0.028 to -0.005]) for FEV1 and -0.437 ± 0.073 ml·min -1·mmHg-1·year-1 with EXU and -0.287 ± 0.065 ml·min-1·mmHg -1·year-1with SC insulin (nonsignificant mean difference -0.150 ml·min-1·mmHg -1·year-1 [-0.310 to 0.011]) for DLCO. The mean annual rates of change in FEV1 between months 3 and 24 were -0.041 ± 0.005 and -0.031 ± 0.006 l/year in the EXU and SC insulin groups, respectively (nonsignificant mean difference -0.011 l/year [-0.023 to 0.002]), indicating that the significant difference between the treatment groups in FEV1 developed during the first 3 months and was not progressive thereafter. Adverse event profiles were similar except for a higher incidence of cough (usually mild and unproductive) in patients receiving EXU (37.6 vs. 13.1{\%}) that decreased to 1.3{\%} by month 24. Glycemic control was sustained in both groups (adjusted mean treatment difference in change from baseline A1C at month 24 0.25 ± 0.07{\%} [0.13-0.37]). Although the overall hypoglycemic events were comparable between groups (4.0 vs. 3.8 events/subject-month), the incidence of severe hypoglycemic events was lower with EXU than with SC insulin (2.8 vs. 4.1 events/100 subject-months, risk ratio 0.67 [0.57-0.79]). Body weight increased to a significantly lesser extent with EXU (adjusted mean treatment difference -1.25 ± 0.36 kg [-1.85 to -0.66]). CONCLUSIONS - Treatment group differences in lung function between EXU and SC insulin in adult patients with type 1 diabetes are small, develop early, and are nonprogressive for up to 2 years of therapy.",
author = "Skyler, {Jay S} and Lois Jovanovic and Sol Klioze and Joann Reis and William Duggan",
year = "2007",
month = "3",
day = "1",
doi = "10.2337/dc06-1863",
language = "English",
volume = "30",
pages = "579--585",
journal = "Diabetes Care",
issn = "1935-5548",
publisher = "American Diabetes Association Inc.",
number = "3",

}

TY - JOUR

T1 - Two-year safety and efficacy of inhaled human insulin (exubera) in adult patients with type 1 diabetes

AU - Skyler, Jay S

AU - Jovanovic, Lois

AU - Klioze, Sol

AU - Reis, Joann

AU - Duggan, William

PY - 2007/3/1

Y1 - 2007/3/1

N2 - OBJECTIVE - The purpose of this study was to evaluate the long-term (2-year) safety and efficacy of inhaled human insulin (Exubera [insulin human (rDNA origin)] inhalation powder) (EXU) in adult patients with type 1 diabetes. RESEARCH DESIGN AND METHODS - Patients were randomly assigned to receive EXU (n = 290) or subcutaneous (SC) insulin (n = 290), plus basal (intermediate- or long-acting) insulin. The primary end point was the annual rate of decline in pulmonary function (forced expiratory volume in 1 s [FEV1] and carbon monoxide diffusing capacity [DLCO]). RESULTS - The mean ± SEM annual rates of change between months 0 and 24 were -0.051 ± 0.005 l/year with EXU and -0.034 ± 0.005 l/year with SC insulin (significant mean difference -0.017 ± 0.007 l/year [90% CI -0.028 to -0.005]) for FEV1 and -0.437 ± 0.073 ml·min -1·mmHg-1·year-1 with EXU and -0.287 ± 0.065 ml·min-1·mmHg -1·year-1with SC insulin (nonsignificant mean difference -0.150 ml·min-1·mmHg -1·year-1 [-0.310 to 0.011]) for DLCO. The mean annual rates of change in FEV1 between months 3 and 24 were -0.041 ± 0.005 and -0.031 ± 0.006 l/year in the EXU and SC insulin groups, respectively (nonsignificant mean difference -0.011 l/year [-0.023 to 0.002]), indicating that the significant difference between the treatment groups in FEV1 developed during the first 3 months and was not progressive thereafter. Adverse event profiles were similar except for a higher incidence of cough (usually mild and unproductive) in patients receiving EXU (37.6 vs. 13.1%) that decreased to 1.3% by month 24. Glycemic control was sustained in both groups (adjusted mean treatment difference in change from baseline A1C at month 24 0.25 ± 0.07% [0.13-0.37]). Although the overall hypoglycemic events were comparable between groups (4.0 vs. 3.8 events/subject-month), the incidence of severe hypoglycemic events was lower with EXU than with SC insulin (2.8 vs. 4.1 events/100 subject-months, risk ratio 0.67 [0.57-0.79]). Body weight increased to a significantly lesser extent with EXU (adjusted mean treatment difference -1.25 ± 0.36 kg [-1.85 to -0.66]). CONCLUSIONS - Treatment group differences in lung function between EXU and SC insulin in adult patients with type 1 diabetes are small, develop early, and are nonprogressive for up to 2 years of therapy.

AB - OBJECTIVE - The purpose of this study was to evaluate the long-term (2-year) safety and efficacy of inhaled human insulin (Exubera [insulin human (rDNA origin)] inhalation powder) (EXU) in adult patients with type 1 diabetes. RESEARCH DESIGN AND METHODS - Patients were randomly assigned to receive EXU (n = 290) or subcutaneous (SC) insulin (n = 290), plus basal (intermediate- or long-acting) insulin. The primary end point was the annual rate of decline in pulmonary function (forced expiratory volume in 1 s [FEV1] and carbon monoxide diffusing capacity [DLCO]). RESULTS - The mean ± SEM annual rates of change between months 0 and 24 were -0.051 ± 0.005 l/year with EXU and -0.034 ± 0.005 l/year with SC insulin (significant mean difference -0.017 ± 0.007 l/year [90% CI -0.028 to -0.005]) for FEV1 and -0.437 ± 0.073 ml·min -1·mmHg-1·year-1 with EXU and -0.287 ± 0.065 ml·min-1·mmHg -1·year-1with SC insulin (nonsignificant mean difference -0.150 ml·min-1·mmHg -1·year-1 [-0.310 to 0.011]) for DLCO. The mean annual rates of change in FEV1 between months 3 and 24 were -0.041 ± 0.005 and -0.031 ± 0.006 l/year in the EXU and SC insulin groups, respectively (nonsignificant mean difference -0.011 l/year [-0.023 to 0.002]), indicating that the significant difference between the treatment groups in FEV1 developed during the first 3 months and was not progressive thereafter. Adverse event profiles were similar except for a higher incidence of cough (usually mild and unproductive) in patients receiving EXU (37.6 vs. 13.1%) that decreased to 1.3% by month 24. Glycemic control was sustained in both groups (adjusted mean treatment difference in change from baseline A1C at month 24 0.25 ± 0.07% [0.13-0.37]). Although the overall hypoglycemic events were comparable between groups (4.0 vs. 3.8 events/subject-month), the incidence of severe hypoglycemic events was lower with EXU than with SC insulin (2.8 vs. 4.1 events/100 subject-months, risk ratio 0.67 [0.57-0.79]). Body weight increased to a significantly lesser extent with EXU (adjusted mean treatment difference -1.25 ± 0.36 kg [-1.85 to -0.66]). CONCLUSIONS - Treatment group differences in lung function between EXU and SC insulin in adult patients with type 1 diabetes are small, develop early, and are nonprogressive for up to 2 years of therapy.

UR - http://www.scopus.com/inward/record.url?scp=33847678166&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847678166&partnerID=8YFLogxK

U2 - 10.2337/dc06-1863

DO - 10.2337/dc06-1863

M3 - Article

C2 - 17327324

AN - SCOPUS:33847678166

VL - 30

SP - 579

EP - 585

JO - Diabetes Care

JF - Diabetes Care

SN - 1935-5548

IS - 3

ER -