Inhaled insulin provides improved glycemic control in patients with type 2 diabetes mellitus inadequately controlled with oral agents: a randomized controlled trial

BACKGROUND: The long-term benefits of good glycemic control are well established. The aim of this proof-of-concept study was to determine whether glycemic control can be improved in patients with type 2 diabetes mellitus with suboptimal glycemic control, despite therapeutic dosages of oral antihyperglycemic agents (OHAs), by the addition of preprandial inhaled insulin (INH). METHODS: Sixty-eight patients with inadequately controlled type 2 diabetes mellitus (glycosylated hemoglobin, 8.1%-11.9%), despite therapy with a sulfonylurea and/or metformin, were randomized to receive INH in addition to their prestudy OHA therapy (INH + OHA group, n = 32) or to continue taking their prestudy OHA alone for 12 weeks (OHA group, n = 36). Premeal INH doses were delivered in 1 to 2 inhalations of 1-mg or 3-mg doses (equivalent to 3 IU and 9 IU, respectively, of subcutaneously injected regular insulin). RESULTS: At week 12, there was a significantly greater reduction in glycosylated hemoglobin for the INH + OHA cohort (mean reduction, -2.3%) compared with the OHA-only cohort (mean reduction, -0.1%, P<.001). Eleven patients (34%) receiving INH + OHA achieved glycosylated hemoglobin values of less than 7%, compared with none taking OHAs only. Fasting plasma glucose improved significantly more in the INH + OHA group compared with the OHA-only group (-60.69 mg/dL (-3.37 mmol/L] greater reduction, P<.001), and the postprandial increase in glucose was significantly lower in those patients receiving INH + OHA (P =.02). There was 1 report of severe hypoglycemia in the INH + OHA group (home blood glucose, 54 mg/dL [3.0 mmol/L]) and a greater increase in body weight. Pulmonary function was unchanged in both groups. CONCLUSION: The addition of preprandial INH to existing OHAs improves glycemic control without the need for injections in patients with type 2 diabetes mellitus failing to achieve satisfactory control with OHAs alone.