Improving Efficacy of Inhaled Technosphere Insulin (Afrezza) by Postmeal Dosing: In-silico Clinical Trial with the University of Virginia/Padova Type 1 Diabetes Simulator

Diabetes Technol Ther. 2016 Sep;18(9):574-85. doi: 10.1089/dia.2016.0128. Epub 2016 Jun 22.


Background: Technosphere(®) insulin (TI), an inhaled human insulin with a fast onset of action, provides a novel option for the control of prandial glucose. We used the University of Virginia (UVA)/Padova simulator to explore in-silico the potential benefit of different dosing regimens on postprandial glucose (PPG) control to support the design of further clinical trials. Tested dosing regimens included at-meal or postmeal dosing, or dosing before and after a meal (split dosing).

Methods: Various dosing regimens of TI were compared among one another and to insulin lispro in 100 virtual type-1 patients. Individual doses were identified for each regimen following different titration rules. The resulting postprandial glucose profiles were analyzed to quantify efficacy and the risk for hypoglycemic events.

Results: This approach allowed us to assess the benefit/risk for each TI dosing regimen and to compare results with simulations of insulin lispro. We identified a new titration rule for TI that could significantly improve the efficacy of treatment with TI.

Conclusion: In-silico clinical trials comparing the treatment effect of different dosing regimens with TI and of insulin lispro suggest that postmeal dosing or split dosing of TI, in combination with an appropriate titration rule, can achieve a superior postprandial glucose control while providing a lower risk for hypoglycemic events than conventional treatment with subcutaneously administered rapid-acting insulin products.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Computer Simulation
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Drug Administration Schedule
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / therapeutic use
  • Insulin / administration & dosage*
  • Insulin / therapeutic use
  • Postprandial Period


  • Hypoglycemic Agents
  • Insulin