Assessing the impact of a new delivery method of insulin on glycemic control using a novel trial design

Objective: The purpose of the trial was to examine the impact of inhaled human insulin (INH) on patient or physician willingness to adopt insulin after oral diabetes agent failure. Research design and methods: The EXPERIENCE trial was a one-year randomized controlled trial conducted at primary, secondary and tertiary care facilities in Europe and North America. The primary study endpoint was difference in glycated hemoglobin (A(1c)) between randomized groups at 26 weeks, and results from that phase have been reported previously. The present report concerns results from the second 26-week extension phase. We also consider the applicability of the design. The trial recruited 727 patients with type 2 diabetes mellitus who, prior to randomization, were using two or more oral diabetes agents and whose A(1c) was >= 8.0%. Patients were randomized to two treatment settings: Group 1 (usual care with the option of INH) or Group 2 (usual care only). Usual care included adjusting oral therapy (optimizing current regimen or adding/deleting agents) and/or initiating subcutaneous (SC) insulin. Results: At baseline, insulin was initiated by more (odds ratio [OR] 6.0; 95% confidence interval [CI] 4.2 to 8.8; P < 0.0001) patients in Group 1 (86.2%; 76.7% INH plus 9.5% SC) than in Group 2 (50.7%; SC insulin only). The largest reduction from baseline in A(1c) was in Group 1 (-2.0 +/- 1.2%) at Week 12 and in Group 2 (-1.8 +/- 1.3%) at Week 26 (P = 0.003). At 52 weeks, 79.8% were on insulin in Group 1 (67.4% INH; 12.4% SC) vs 58.1% (SC only) in Group 2, and mean (SD) changes in A 1c from baseline were-1.9% (1.2%) and-1.8% (1.3%) in Groups 1 and 2, respectively (P = 0.05). Hypoglycemic event rates per patient month were 0.3 and 0.1 in Groups 1 and 2, respectively (P < 0.0001). Conclusion: The EXPERIENCE trial showed that novel delivery technology can accelerate the adoption of insulin although some attenuation of differences is observed over time. And further, that this was achieved in a population of patients who appeared more ready to move to insulin therapy than observed in standard clinical practice, and a group of physicians who appeared more ready to adopt INH than the majority of physicians.