Incorporating Long-Acting Insulin Glargine Into the UVA/Padova Type 1 Diabetes Simulator for In Silico Testing of MDI Therapies

IEEE Trans Biomed Eng. 2019 Oct;66(10):2889-2896. doi: 10.1109/TBME.2019.2897851. Epub 2019 Feb 6.


Objective: Glargine 100 U/mL (Gla-100) and 300 U/mL (Gla-300) are long-acting insulin analogs providing basal insulin supply in multiple daily injection (MDI) therapy of type 1 diabetes (T1D). Both insulins require extensive testing to arrive at the optimal dosing regimen, e.g., timing and amount. Here we aim at a simulation tool for evaluating benefits/risks of different dosing schemes and up-titration rules for both Gla-100 and Gla-300 before clinical testing.

Methods: A new pharmacokinetic (PK) model of both Gla-100 and Gla-300 was incorporated into the FDA-accepted University of Virginia/Padova T1D simulator: Specifically, a joint parameter distribution, built from PK parameter estimates, was used to generate individual PK parametrizations for each in silico subject. A virtual trial comparing Gla-100 vs. Gla-300 was performed and assessed against a clinical study to validate the glargine simulator.

Results: Like in vivo, in silico both insulins performed similarly with respect to glucose control: percent time of glucose between [80-140] mg/dL with Gla-100 vs. Gla-300 (primary endpoint) were 41.5 ± 1.1% vs. 39.0 ± 1.2% (P = 0.11) in silico, 31.0 ± 1.6% vs. 31.8 ± 1.5% (P = 0.73) in vivo.

Conclusions: The glargine simulator reproduced the main findings of the clinical trial, proving its validity for testing MDI therapies.

Significance: In silico testing of MDI therapies can help designing clinical trials. Due to the more standardized settings in silico (e.g., standardized meals and strict adherence to titration rule), any potential treatment effect is reaching statistical significance in simulation vs. clinical trial.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Blood Glucose / analysis
  • Computer Simulation
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Drug Administration Schedule
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / pharmacokinetics*
  • Injections
  • Insulin Glargine / administration & dosage*
  • Insulin Glargine / pharmacokinetics*
  • Insulin, Long-Acting


  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin, Long-Acting
  • Insulin Glargine