Preliminary study of the efficacy of insulin aerosol delivered by oral inhalation in diabetic patients.

ABSTRACT

OBJECTIVE: To maximize deposition of an aerosolized dose of insulin (mean +/- SD = 0.99 +/- 0.06 U/kg of body weight) in the lungs of subjects with non-insulin-dependent diabetes mellitus (NIDDM), and investigate its efficacy in normalizing plasma glucose levels during the fasting state. DESIGN: Nonrandomized, placebo-controlled trial. SETTING: A primary care facility. PATIENTS OR OTHER PARTICIPANTS: Six nonobese, nonsmoking volunteers with NIDDM. No subjects withdrew from the study. INTERVENTION Aerosolized insulin was administered by oral inhalation after a 12-hour period of fasting. Aerosol was generated by a raindrop nebulizer from regular 500 U/mL pork insulin. During inhalation, inspiratory flow was regulated at 17 L/min. Plasma samples were collected after inhalation and analyzed for insulin and glucose levels. MAIN OUTCOME MEASURES: 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 insulin level was 71 pmol/L (11.8 microU/mL), rising to 269 pmol/L (44.8 microU/mL) after insulin inhalation. Average time to peak insulin level was 40 +/- 34 minutes. The mean fasting plasma glucose level (12.63 +/- 2.59 mmol/L [225.5 +/- 46.3 mg/dL]) was reduced to within the normal range in five subjects and was almost normal in the sixth subject (5.52 +/- 0.89 mmol/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 inhalation (n = 3). No side effects were reported following insulin or placebo aerosol inhalation. CONCLUSIONS: These preliminary results indicate that a dose of approximately 1.0 U of aerosolized insulin per kilogram of body weight, delivered by oral inhalation and deposited predominantly within the lungs, is well tolerated and can effectively normalize plasma glucose levels in patients with NIDDM.