Effect of Afrezza on Glucose Dynamics During HCL Treatment

Abstract

Objective: A major obstacle in optimizing the performance of closed-loop automated insulin delivery systems has been the delay in insulin absorption and action that results from the subcutaneous (SC) route of insulin delivery leading to exaggerated postmeal hyperglycemic excursions. We aimed to investigate the effect of Afrezza inhaled insulin with ultrafast-in and -out action profile on improving postprandial blood glucose control during hybrid closed-loop (HCL) treatment in young adults with type 1 diabetes.

Research design and methods: We conducted an inpatient, three-way, randomized crossover standardized meal study to assess the efficacy and safety of Afrezza at a low (AL) and a high (AH) dose as compared with a standard SC rapid-acting insulin (aspart) premeal bolus during Diabetes Assistant (DiAs) HCL treatment. Participants received two sequential meals on three study days, and premeal insulin bolus was determined based on home insulin-to-carbohydrate ratio for each meal (rounded up to the closest available Afrezza cartridge dose for AH and down for AL). The primary efficacy outcome was the peak postprandial plasma glucose (PPG) level calculated by pooling data for up to 4 h after the start of each meal. Secondary outcomes included hyperglycemic, hypoglycemic, and euglycemic venous glucose metrics.

Results: The mean ± SD PPG for the rapid-acting insulin control arm and AH was similar (185 ± 50 mg/dL vs. 195 ± 46 mg/dL, respectively; P = 0.45), while it was higher for meals using AL (208 ± 54 mg/dL, P = 0.04). The AH achieved significantly lower early PPG level than the control arm (30 min; P < 0.001), and improvement in PPG waned at later time points (120 and 180 min; P = 0.02) coinciding with the end of Afrezza glucodynamic action.

Conclusions: Afrezza (AH) premeal bolus reduced the early glycemic excursion and improved PPG during HCL compared with aspart premeal bolus. The improvement in PPG was not sustained after the end of Afrezza glucodynamic action at 120 min.

Trial registration: ClinicalTrials.gov NCT03234491.

© 2020 by the American Diabetes Association.

Figures

Figure 1

Comparison of venous glucose levels (upper panels), serum insulin (middle panels), and basal insulin infusion rates (lower panels) over time between the Afrezza arms and the control arm.