PRELIMINARY-STUDY OF THE EFFICACY OF INSULIN AEROSOL DELIVERED BY ORAL INHALATION IN DIABETIC-PATIENTS

Objective.-To maximize deposition of an aerosolized dose of insulin (m ean+/-SD=0.99+/-0.06 U/kg of body weight) in the lungs of subjects wit h non-insulin-dependent diabetes mellitus (NIDDM), and investigate its efficacy in normalizing plasma glucose levels during the fasting stat e. Design.-Nonrandomized, placebo-controlled trial. Setting.-A primary care facility. Patients or Other Participants.-Six nonobese, nonsmoki ng volunteers with NIDDM. No subjects withdrew from the study. Interve ntion.-Aerosolized insulin was administered by oral inhalation after a 12-hour period of fasting. Aerosol was generated by a raindrop nebuli zer from regular 500 U/mL pork insulin. During inhalation, inspiratory flow was regulated at 17 L/min. Plasma samples were collected after i nhalation and analyzed for insulin and glucose levels. Main Outcome Me asures.-Plasma insulin and glucose levels. Results.-Deposition of the aerosol was maximized within the lungs, with 79% +/-17% of the inhaled dose depositing below the larynx. Geometric mean fasting plasma insul in level was 71 pmol/L (11.8 muU/mL), rising to 269 pmol/L (44.8 muU/m L) after insulin inhalation. Average time to peak insulin level was 40 +/-34 minutes. The mean fasting plasma glucose level (12.63+/-2.59 mmo l/L [225.5+/-46.3 mg/dL]) was reduced to within the normal range in fi ve subjects and was almost normal in the sixth subject (5.52+/-0.89 mm ol/L [98.6+/-15.9 mg/dL]). Average maximum decrease in plasma glucose from baseline was 55%+/-10% (n=6) vs 13%-9% after placebo aerosol inha lation (n=3). No side effects were reported following insulin or place bo aerosol inhalation. Conclusions.-These preliminary results indicate that a dose of approximately 1.0 U of aerosolized insulin per kilogra m of body weight, delivered by oral inhalation and deposited predomina ntly within the lungs, is well tolerated and can effectively normalize plasma glucose levels in patients with NIDDM.