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Type 2 Diabetes Poorly Controlled With Sulfonylurea Improved by Adding Inhaled I

Jun 20, 2006

Patients with type 2 diabetes receiving poor control while taking sulfonylurea improve more by adding inhaled insulin vs metformin, according to the results of an open-label, randomized study, "Inhaled human insulin (INH; Exubera [insulin human (rDNA origin inhalation powder)]) is a dry-powder formulation and inhaler system developed by Pfizer in collaboration with Nektar Therapeutics that has recently been approved in both the U.S. and European Union for the treatment of type 1 and type 2 diabetes in adults," write Anthony H. Barnett, BSc, MD, FRCP, from the University of Birmingham and Heart of England National Health Service Foundation Trust in Birmingham, United Kingdom, and colleagues. "INH therapy has proven effective in patients failing to obtain adequate glycemic control with diet and exercise, has demonstrated improved glycemic control compared with oral antidiabetic agents, and has been shown to be comparable to subcutaneously injected insulin."

In this 24-week, multicenter trial, patients uncontrolled while receiving sulfonylurea monotherapy were divided at week 1 into 2 glycated hemoglobin (HbA1c) groups: 8% or more to 9.5% or less (moderately high) and more than 9.5% to 12% or less (very high). Patients were randomized to adjunctive premeal INH (n = 225) or to metformin (n = 202), and the main efficacy outcome was change in HbA1c level from baseline.

In the HbA1c more than 9.5% group, there was a significantly greater reduction in HbA1c level from baseline with INH than with metformin (-2.17% vs -1.79%; between-treatment difference, -0.38%; 95% confidence interval [CI], -0.63 to -0.14; P = .002).

In the HbA1c 9.5% or less group, mean adjusted HbA1c changes were -1.94% vs -1.87% (between-treatment difference, -0.07%; 95% CI, -0.33 to 0.19; P = .610), consistent with the noninferiority criterion. Although hypoglycemia events per subject-month were increased in the INH group (0.33) compared with the metformin group (0.15; risk ratio, 2.16; 95% CI, 1.67 – 2.78), there were no associated discontinuations. Other adverse events were similar between groups, except for increased cough in the INH group. Changes in pulmonary function parameters at week 24 were small and similar in both groups. Insulin antibody binding increased more with INH, but there were no associated clinical manifestations.

"In patients with type 2 diabetes poorly controlled on a sulfonylurea (HbA1c > 9.5%), the addition of premeal INH significantly improves glycemic control compared with adjunctive metformin and is well tolerated," the authors write.

Study limitations include open-label design and patients failing to respond to sulfonylurea therapy, suggesting that they already had significant beta-cell dysfunction.

"The results of this study demonstrate that adding INH to sulfonylurea therapy provides effective glycemic control and may be an alternative to oral agent combination therapy in patients with type 2 diabetes," the authors conclude. "The results corroborate findings from a similar study in which adjunctive INH was compared with the addition of a sulfonylurea (glibenclamide [glyburide]) in patients poorly controlled with metformin. Together, these studies suggest that new ways of delivering insulin without the need for injections may help in the early adoption of insulin treatment by patients and assist in achieving and maintaining long-term optimal glycemic control.

Pfizer, the maker of INH, supported this study. Two of the authors have disclosed financial relationships with Eli Lilly, Novo Nordisk, Roche, Sanofi-Aventis, GlaxoSmithKline, and/or Astra Zeneca. The costs of publication of this article were defrayed in part by the payment of page charges, mandating that it be hereby marked "advertisement."

Diabetes Care. 2006;29:1282-1287


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