A software interface for in silico testing of type 2 diabetes treatments

Abstract

Background and objective: The increasing incidence of diabetes continuously stimulates the research on new antidiabetic drugs. Computer simulation can save time and costs, alleviating the need of animal trials and providing useful information for optimal experiment design and drug dosing. We recently presented a type 2 diabetes (T2D) simulator as tool for in silico testing of new molecules and guiding treatment optimization. Here we present a user-friendly interface aimed to increase the usability of the simulator.

Method: The simulator, based on a large-scale glucose, insulin, and C-peptide model and equipped with 100 virtual subjects well describing system dynamics in a real T2D population, is extended to incorporate pharmacokinetics/pharmacodynamics (PK/PD) of a drug of interest. A graphical interface is developed on top of the simulator, allowing an easy design of in silico experiments: specifically, it is possible to select the population size to test, design the experiment (crossover or parallel), its duration and the sampling grid, choose glucose and insulin doses, and define treatment PK/PD and dose administered. The simulator also provides the outcome metrics requested by the user, and performs statistical comparisons among treatments and/or placebo.

Results: To illustrate the potential of the simulator, we provided a case study using metformin and liraglutide. Literature-based PK/PD models of metformin and liraglutide have been incorporated in the simulator, by modulating key drug-sensitive model parameters. An in silico placebo-controlled trial has been done by simulating a three-arm meal tolerance test with subjects receiving placebo, metformin 850 mg, liraglutide 1.80 mg, respectively. The obtained results are in agreement with the clinical evidences, in terms of main glucose, insulin, and C-peptide outcome metrics.

Conclusions: We developed a user-friendly software interface for the T2D simulator to support the design and test of new antidiabetic drugs and treatments. This increases the simulator usability, making it suitable also for users who have low experience with computer programming.

Keywords: Computer simulation; Diabetes control; Glucose regulation; In silico trials; Modeling; Pharmacokinetics-pharmacodynamics.