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Effect of Inhaled Insulin on Fasting and Postprandial Plasma Glucose

Lisa Ceglia, MD; Joseph Lau, MD; and Anastassios G. Pittas, MD, MSc
[+] Article, Author, and Disclosure Information

From Tufts-New England Medical Center, Boston, MA 02111.

Potential Financial Conflicts of Interest: None disclosed.

Ann Intern Med. 2007;146(11):821-822. doi:10.7326/0003-4819-146-11-200706050-00017
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Inhaled insulin too fast and powerful in FDA label
Posted on June 28, 2007
Bjorn E. Belfrage
Department of Clinical Pharmacology, Karolinska University Hospital, Stockholm, Sweden
Conflict of Interest: None Declared

Mikhail and collegues raise the interesting topic of fasting and postprandial plasma glucose with inhaled insulin (1). On their request Ceglia and collegues expanded their meta-analysis (2) to include these variables. No significant differences in postprandial glucose levels between inhaled and injected meal insulin were seen (1).

However, none of the studies included in the meta-analysis compared the inhaled insulin (Exubera) group with a group receiving a subcutaneous insulin analogue as the only meal insulin. To my knowledge no such studies have been published.

It is tempting to draw conclusions about the postprandial glucose control with inhaled insulin compared to injected analogues from the agency-approved product information for Exubera. However, it includes a misleading presentation, making Exubera seem more fast-acting and more powerful than the original data actually show.

According to the original data, presented in Diabetes Care -05 (3), the maximum effect of Exubera is approximately 20 percent weaker than the maximum effect of an equipotent dose (96 percent of AUC) of subcutaneous insulin lispro. The effect of insulin lispro continues to be stronger than the Exubera effect for approximately five hours after the insulin administration. The glucose infusion rate ("GIR") needed to keep the glucose level constant is used as a measure of insulin effect. The effect of subcutaneous human insulin is also shown. See "figure 1A" on page 1078 at http://care.diabetesjournals.org/cgi/reprint/28/5/1077.

The same data is presented quite differently in the drug information approved by the FDA and EMEA (4,5), see "figure 2" on page 3 at http://www.fda.gov/cder/foi/label/2006/021868lbl.pdf. By using percent of maximum individual GIR values on the vertical axis, the curve belonging to Exubera starts rising earlier, and rises higher than the curves from the two other insulins giving the impression of a faster and more powerful effect. The same figure can be found in a Pfizer document (6) where the accompanying data exactly match the data from the Diabetes Care article.

Since a higher proportion of the lispro effect occurs within the first few hours after dosing, it would be interesting to see if that gives an advantage over Exubera in terms of postprandial glucose control. Even if it doesn't, and although the agency-approved figure doesn't lie, the different exuberance of inhaled insulin in the two figures is striking.


1. Mikhail NE, Wali S, Cope D. Effect of inhaled insulin on fasting and postprandial plasma glucose. Ann Intern Med. 2007 Jun 5;146(11):821; author reply by Ceglia and collegues: 821-2.

2. Ceglia L, Lau J, Pittas AG. Meta-analysis: efficacy and safety of inhaled insulin therapy in adults with diabetes mellitus. Ann Intern Med. 2006 Nov 7;145(9):665-75.

3. Rave K, Bott S, Heinemann L, Sha S, Becker RH, Willavize SA, Heise T. Time-action profile of inhaled insulin in comparison with subcutaneously injected insulin lispro and regular human insulin. Diabetes Care. 2005 28(5):1077-82.

4. Exubera, summary of product characteristics approved by the EMEA 2007-03-08. http://www.emea.europa.eu/humandocs/PDFs/EPAR/exubera/H-588-PI -en.pdf

5. Exubera, label approved by the FDA 2006-01-27. http://www.fda.gov/cder/foi/label/2006/021868lbl.pdf

6. Advisory Committee Briefing Document. Exubera. Pfizer. 2005-08-03. Page 55. http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4169B1_01_01 -Pfizer-Exubera.pdf

Conflict of Interest:

None declared

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