Article Summary Efficacy of inhaled insulin in patients with type 2 diabetes not controlled with diet and exercise: a 12-week, randomized, comparative trial. DeFronzo RA, Bergenstal RM, Cefalu WT, Pullman J, Lerman S, Bode BW, Phillips LS, for the Exubera Phase III Study Group. Diabetes Care. 2005;28:1922-1928. Objective: To determine whether use of inhaled insulin (INH) can assist the patient who has type 2 diabetes in achieving target glycemic control when nonpharmacologic means, such as diet and exercise, have not been effective. Methods: A total of 145 eligible patients with type 2 diabetes were enrolled in an open-label, parallel-group, multicenter study with a 4-week lead-in phase and a 12-week randomized treatment phase. During the lead-in phase, patients were required to attend an American Diabetes Association (ADA) instructional session on recommended diet and exercise; they were instructed to maintain a daily diet that adhered to ADA recommendations and to perform 30 minutes of moderate intensity exercise on at least 3 days per week and were taught how to use a new glucose test meter. During the treatment phase, eligible patients were randomly assigned to receive INH within 10 minutes before each meal or rosiglitazone at a dose of 4 mg twice daily; they were also required to perform self-monitoring blood glucose at least 4 times each day. Observations: The proportion of patients who reached the primary study endpoint of A1C <8% was significantly higher in the INH group than in the rosiglitazone group (82.7% vs 58.2%); similar findings revealed that 44.0% of the INH group (vs 17.9% of those taking rosiglitazone) achieved the ADA-recommended goal of A1C <7%, and that 28.0% versus 7.5% reached an A1C ≤6.5% (INH vs rosiglitazone, respectively). Findings were comparable between treatment groups on secondary study endpoints, which included changes in A1C, fasting plasma glucose, 2-hour postprandial plasma glucose following a standardized meal, and fasting serum lipids. A greater proportion of those in the INH group experienced treatment-related adverse events compared with the rosiglitazone group (51 and 22 patients, respectively). Most, however, were of mild to moderate severity, with hypoglycemia reported most often. Conclusions: This study demonstrated that the use of INH in a group of patients with type 2 diabetes that was not well controlled with diet and exercise resulted in the attainment of defined targets of glycemic control. Because it offers a potential strategy for enhancing control of glycemia, insulin therapy, particularly that provided through a noninvasive delivery system, is being considered earlier in the treatment program for patients with type 2 diabetes. INH monotherapy was shown to work more quickly than rosiglitazone in improving glycemic control and was well tolerated by study patients. All treatment-related adverse events noted with INH were mild or moderate; the most commonly reported adverse event was hypoglycemia.