Article Summary Efficacy and Safety of Inhaled Insulin (Exubera) Compared With Subcutaneous Insulin Therapy in Patients With Type 2 Diabetes. Results of a 6-month, randomized, comparative trial. Hollander PA, Blonde L, Rowe R, Mehta AE, Milburn JL, Hershon KS, Chiasson JL, Levin SR, for the EXUBERA Phase III Study Group. Diabetes Care. 2004;27:2356-2362. Objective: To compare the efficacy and tolerability of inhaled insulin with that of conventional subcutaneous insulin in patients with type 2 diabetes. Methods: This phase 3, open-label, parallel-group comparator study included 520 patients who were diagnosed with type 2 diabetes and screened at 39 medical centers in the United States and Canada. All study patients had been treated with 2 to 3 subcutaneous insulin injections (SCII) daily for at least 2 months and were not receiving any oral antihyperglycemic agents. The primary efficacy end point was change in A1C from baseline to end of study. Prior to randomization, the A1C value of study patients was 6% to 11%. All patients received instruction on the importance of diet and exercise for weight maintenance, as well as training in self-management of blood glucose, which they were to perform 4 times daily. Although the trial was designed to show equivalence of the treatment regimens rather than target glucose ranges, preprandial glucose targets were 80 mg/dL to 140 mg/dL, and bedtime targets were 100 mg/dL to 160 mg/dL. Patients were randomized to receive an inhaled insulin regimen (n=149) or to continue pretrial SCII (n=150) for 24 weeks. The inhaled insulin treatment arm consisted of premeal inhaled insulin administered within 10 minutes of the start of each meal using a dry-powder aerosol delivery system and 1 bedtime injection of ultralente insulin. Patients in the SCII arm administered self-injections of mixed NPH/regular insulin before breakfast and supper. Results: Decreases in mean A1C were similar in the 2 treatment groups (8.1% at baseline to 7.4% at week 24 in the inhaled insulin group; 8.2% to 7.6% in the SCII arm), which suggests that the regimens are statistically comparable. Forty-seven percent of patients in the former group achieved A1C <7% at week 24 versus 32% of patients receiving SCII. In the inhaled insulin treatment group, fasting plasma glucose and postprandial plasma glucose decreased from 152 mg/dL at baseline to 132 mg/dL at week 24, versus 158 mg/dL to 149 mg/dL in the SCII group. A total of 1104 hypoglycemic events occurred in the inhaled insulin group (4 classed as severe) versus 1278 events in the SCII group (1 classified as severe). Mean body weight remained stable at week 24 in the inhaled insulin group versus a slight increase in mean body weight (1.4 kg) in the SCII group. Frequency of adverse events was similar between the 2 treatment arms, with the exception of cough in the inhaled insulin arm. Cough decreased in incidence over the study period. A significant improvement in the mean overall satisfaction score was reported for the inhaled insulin group. Favorable improvements in the quality-of-life scale were also seen in the inhaled insulin group. Conclusion: Reluctance by patients and physicians to initiate insulin therapy results in poor quality of life and increases the risk of microvascular and macrovascular complications. Inhaled insulin may be a viable treatment option for patients with type 2 diabetes, particularly in patients for whom the ability to self-inject SCII may be emotionally or physically problematic.