Effect of Afrezza on glucose dynamics during HCL treatment

Objective: A major obstacle in optimizing the performance of closed-loop (CL) 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 post-meal hyperglycemic excursions. We aimed to investigate the effect of Afrezza inhaled insulin with ultrafast-in and out action profile on improving post-prandial blood glucose control during hybrid closed loop (HCL) treatment in young adults with type 1 diabetes.

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

Results: The mean PPG for the rapid acting insulin control arm and A_H were similar (185±50mg/dL vs. 195±46mg/dL, respectively; p=0.45), while it was higher for meals using A_L (208±54mg/dL, p=0.04). The A_H 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 (A_H) pre-meal bolus reduced the early glycemic excursion and improved PPG during HCL compared to aspart pre-meal bolus. The improvement in PPG was not sustained after the end of Afrezza glucodynamic action at 120min.