Background: Insulin therapy is often a delayed strategy in patients with type 2 diabetes mellitus because it is associated with weight gain, hypoglycaemia, and the need for subcutaneous injections. We aimed to assess the efficacy and safety of prandial Technosphere inhaled insulin compared with twice daily biaspart insulin.
Methods: In this randomised, open-label, parallel-group study, adult patients with type 2 diabetes mellitus and poor glycaemic control despite insulin therapy, with or without oral antidiabetes drugs, were enrolled from ten countries between Feb 23, 2006, and Aug 8, 2007. Patients were randomly allocated in a 1:1 ratio to receive 52 weeks' treatment with: prandial Technosphere inhaled insulin powder plus bedtime insulin glargine; or twice daily premixed biaspart insulin (70% insulin aspart protamine suspension and 30% insulin aspart of rDNA origin). The primary endpoint was a comparison of change in glycosylated haemoglobin (HbA(1c)) from baseline to week 52 between treatment groups; the non-inferiority margin was 0.4%. Analysis was by per protocol for non-inferiority testing of the primary endpoint. This study is registered with ClinicalTrials.gov, number NCT00309244.
Findings: 334 patients were allocated to inhaled insulin plus insulin glargine, and 343 to biaspart insulin; 107 patients on inhaled insulin plus insulin glargine and 85 on biaspart insulin discontinued the trial. 211 patients on inhaled insulin plus insulin glargine and 237 on biaspart insulin were included in per-protocol analyses. Change in HbA(1c) with inhaled insulin plus insulin glargine (-0.68%, SE 0.077, 95% CI -0.83 to -0.53) was similar and non-inferior to that with biaspart insulin (-0.76%, 0.071, -0.90 to -0.62). The between-group difference was 0.07% (SE 0.102, 95% CI -0.13 to 0.27). Patients had significantly lower weight gain and had fewer mild-to-moderate and severe hypoglycaemic events on inhaled insulin plus insulin glargine than on biaspart insulin. The safety and tolerability profile was similar for both treatments, apart from increased occurrence of cough and change in pulmonary function in the group receiving inhaled insulin plus insulin glargine.
Interpretation: This study is part of a large clinical development programme addressing the efficacy and tolerability of use of Technosphere inhaled insulin in a wide variety of patients.
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