Titration of Inhaled Human Insulin (Exubera) in a Treat-to-Target Regimen for Patients with Type 2 Diabetes

Objective: This study assessed the feasibility of safely achieving target glycated hemoglobin (A1C) of <= 7% by intensifying structured insulin titration regimens using inhaled human insulin (Exubera (R) [EXU] [Pfizer Inc., New York, NY] [insulin human (recombinant DNA origin)] inhalation powder) in patients with type 2 diabetes inadequately controlled on combination oral antidiabetes agents (OADs). Methods: In a randomized, open-label, parallel, 24-week multicenter trial, 107 type 2 diabetes patients with mean baseline A1C of 8.6% taking two or more OADs were randomized to adjust EXU before meals following either weekly office visits or more intense twice-weekly telephone/office consultations, using a simple but structured insulin titration algorithm seeking to attain specific premeal glucose levels. Primary outcome was the percentage of patients reaching A1C <= 7%; secondary measures were changes in A1C, eight-point self-monitored blood glucose values, postprandial glucose levels during a meal tolerance, and frequency of hypoglycemia. Results: A1C improved whether EXU was systematically titrated once (6.8%) or twice weekly (6.8%), and two-thirds of patients in both groups attained A1C <= 7% (69% and 67%, respectively). Relative to baseline, glucose profiles were reduced at all time points measured, and postprandial glucose levels during meal tolerance improved to a similar extent in both groups. There were 538 hypoglycemic events with twice-weekly and 343 with once-weekly EXU titration; other adverse events were similar between groups. Conclusions: Added to oral therapy, premeal inhaled insulin can safely achieve <= 7% A1C in most patients with type 2 diabetes inadequately controlled while taking two or more OADs if a once-or twice-weekly structured insulin titration regimen is used.