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Inhaled Human Insulin Treatment in Patients with Type 2 Diabetes Mellitus

William T. Cefalu, MD; Jay S. Skyler, MD; Ione A. Kourides, MD; William H. Landschulz, MD, PhD; Cecile C. Balagtas, PhD; Shu-Lin Cheng, PhD; Robert A. Gelfand, MD, Inhaled Insulin Study Group*
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From University of Vermont College of Medicine, Burlington, Vermont; University of Miami Medical Center, Miami, Florida; and Pfizer Central Research, Groton, Connecticut.

Presented in abstract form as an oral presentation at the Annual Meeting of the American Diabetes Association, Chicago, Illinois, June 1998.

Acknowledgment: The authors thank Becky Aksdal for her skillful preparation of the manuscript and her valuable editorial assistance.

Grant Support: By Pfizer, Inc. Technology used for this study was licensed from Inhale Therapeutic Systems, San Carlos, California.

Requests for Single Reprints: William T. Cefalu, MD, University of Vermont College of Medicine, UHC Campus, Arnold 3433, One South Prospect Street, Burlington, VT 05401.

Current Author Addresses: Dr. Cefalu: University of Vermont College of Medicine, UHC Campus, Arnold 3433, One South Prospect Street, Burlington, VT 05401.

Dr. Skyler: University of Miami Medical Center, 1500 NW 12th Avenue, Suite 1012 East, Miami, FL 33136.

Dr. Kourides: Clinical and Scientific Affairs, Pfizer, Inc., 235 East 42nd Street, New York, NY 10017.

Drs. Landschulz and Gelfand: Department of Clinical Research, Pfizer, Inc., Eastern Point Road, Groton, CT 06340-8030.

Drs. Balagtas and Cheng: Department of Biometrics and Data Management, Pfizer, Inc., Eastern Point Road, Groton, CT 06340.

Author Contributions: Conception and design: I.A. Kourides, W.H. Landschulz, R.A. Gelfand.

Analysis and interpretation of the data: W.T. Cefalu, J.S. Skyler, I.A. Kourides, W.H. Landschulz, C.C. Balagtas, S.-L. Cheng, R.A. Gelfand.

Drafting of the article: W.T. Cefalu, I.A. Kourides, W.H. Landschulz, C.C. Balagtas, S.-L. Cheng, R.A. Gelfand.

Critical revision of the article for important intellectual content: W.T. Cefalu, J.S. Skyler, I.A. Kourides, W.H. Landschulz, C.C. Balagtas, R.A. Gelfand.

Final approval of the article: W.T. Cefalu, J.S. Skyler, I.A. Kourides, W.H. Landschulz, C.C. Balagtas, R.A. Gelfand.

Provision of study materials or patients: J.S. Skyler, W.H. Landschulz, R.A. Gelfand.

Statistical expertise: C.C. Balagtas, S.-L. Cheng.

Obtaining of funding: R.A. Gelfand.

Administrative, technical, or logistic support: W.H. Landschulz, R.A. Gelfand.

Collection and assembly of data: W.T. Cefalu, W.H. Landschulz, C.C. Balagtas, R.A. Gelfand.

Ann Intern Med. 2001;134(3):203-207. doi:10.7326/0003-4819-134-3-200102060-00011
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Background: Despite demonstrated benefits, intensive insulin therapy has not gained widespread clinical acceptance for several reasons: Multiple daily injections are inconvenient, adherence is a concern, and the time-activity profile may not mimic normal insulin secretion. As such, alternate means of administering insulin are being evaluated.

Objective: To assess the efficacy and safety of pulmonary delivery of insulin in type 2 diabetic patients who require insulin.

Design: Randomized, open-label, 3-month study consisting of a screening visit, a 4-week baseline lead-in phase, and a 12-week treatment phase.

Setting: General clinical research center and outpatient research clinics.

Patients: 26 patients (16 men, 10 women) with type 2 diabetes (average age, 51.1 years; average duration of diabetes, 11.2 years).

Intervention: Patients received inhaled insulin before each meal plus a bedtime injection of ultralente insulin, performed home glucose monitoring, and had weekly adjustment of insulin dose; target level for preprandial plasma glucose was 5.55 to 8.88 mmol/L (100 to 160 mg/dL).

Measurements: Glycemic control (hemoglobin A1c level) obtained at baseline and monthly for 3 months. Pulmonary function tests were done at baseline and at the end of the study.

Results: Inhaled insulin treatment for 3 months significantly improved glycemic control compared with baseline: Mean hemoglobin A1c levels decreased by 0.0071 ± 0.0072 (0.71% ± 0.72%). Patients experienced an average of 0.83 mild to moderate hypoglycemic event per month; no severe events were recorded. Patients showed no significant weight gain or change in pulmonary function compared with baseline.

Conclusions: Pulmonary delivery of insulin in type 2 diabetic patients who require insulin improved glycemic control, was well tolerated, and demonstrated no adverse pulmonary effects. Larger-scale studies are ongoing to provide long-term efficacy and safety data.

*For members of the Inhaled Insulin Study Group, see Appendix.


Grahic Jump Location
Figure 1.
Plasma insulin and plasma glucose responses to inhaled and injected insulin.squarestrianglescirclesTop.Bottom.n

The study was a three-way crossover trial comparing one inhalation of a 3-mg blister of insulin ( ); three inhalations of a 1-mg blister of insulin ( ); and an injection of subcutaneous insulin, 0.15 U/kg of body weight (approximately 10 units, ). Sixteen healthy volunteers received each treatment following an overnight fast on separate days, approximately 1 week apart (Data on file. Pfizer, Inc.). Plasma insulin response to inhaled insulin, 3 mg, versus subcutaneous regular insulin, 10 units. Plasma glucose response to 3 mg of inhaled insulin versus 10 units of regular insulin administered subcutaneously. For both parts of the figure, = 16. To convert mmol/L to mg/dL and pmol/L to U/mL, divide by 0.00259 and 7.175, respectively.

Grahic Jump Location
Grahic Jump Location
Figure 2.
Change in mean hemoglobin A 1c level during the 12-week treatment phase in type 2 diabetic patients receiving inhaled insulin therapy.

Error bars represent 1 SD.

Grahic Jump Location




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Summary for Patients

Treating Type 2 Diabetes with Inhaled Insulin

The summary below is from the full report titled “Inhaled Human Insulin Treatment in Patients with Type 2 Diabetes Mellitus.” It is in the 6 February 2001 issue of Annals of Internal Medicine (volume 134, pages 203-207). The authors are WT Cefalu, JS Skyler, IA Kourides, WH Landschulz, CC Balagtas, S-L Cheng, and RA Gelfand, for the Inhaled Insulin Study Group.


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