OBJECTIVE—Despite the demonstrated benefits of glycemic control, patient acceptance of basal/bolus insulin therapy for type 1 diabetes has been slow. We investigated whether a basal/bolus insulin regimen involving rapid-acting, dry powder, inhaled insulin could provide glycemic control comparable with a basal/bolus subcutaneous regimen.

RESEARCH DESIGN AND METHODS—Patients with type 1 diabetes (ages 12–65 years) received twice-daily subcutaneous NPH insulin and were randomized to premeal inhaled insulin (n = 163) or subcutaneous regular insulin (n = 165) for 6 months.

RESULTS—Mean glycosylated hemoglobin (A1C) decreased comparably from baseline in the inhaled and subcutaneous insulin groups (−0.3 and −0.1%, respectively; adjusted difference −0.16% [CI −0.34 to 0.01]), with a similar percentage of subjects achieving A1C <7%. Although 2-h postprandial glucose reductions were comparable between the groups, fasting plasma glucose levels declined more in the inhaled than in the subcutaneous insulin group (adjusted difference −39.5 mg/dl [CI −57.5 to −21.6]). Inhaled insulin was associated with a lower overall hypoglycemia rate but higher severe hypoglycemia rate. The overall hypoglycemia rate (episodes/patient-month) was 9.3 (inhaled) vs. 9.9 (subcutaneous) (risk ratio [RR] 0.94 [CI 0.91–0.97]), and the severe hypoglycemia rate (episodes/100 patient-months) was 6.5 vs. 3.3 (RR 2.00 [CI 1.28–3.12]). Increased insulin antibody serum binding without associated clinical manifestations occurred in the inhaled insulin group. Pulmonary function between the groups was comparable, except for a decline in carbon monoxide−diffusing capacity in the inhaled insulin group without any clinical correlates.

CONCLUSIONS—Inhaled insulin may provide an alternative for the management of type 1 diabetes as part of a basal/bolus strategy in patients who are unwilling or unable to use preprandial insulin injections.