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Modeling and Evaluation of Murine Diabetic Cardiomyopathy Model
Published on: November 29, 2024
Development and Qualification of a Drug-Disease Modeling Platform to Characterize Clinically Relevant Endpoints in
Puneet Gaitonde1,2, Felipe K Hurtado1, Parag Garhyan3
1Center for Pharmacometrics & Systems Pharmacology, Department of Pharmaceutics, University of Florida, Lake Nona (Orlando), Florida, USA.
Abstract:
Type 2 diabetes mellitus (T2DM) is a chronic, progressive disease characterized by persistently elevated blood glucose concentration (hyperglycemia). We developed a mechanistic drug-disease modeling platform based on data from more than 4,000 T2DM subjects in seven phase II/III clinical trials. The model integrates longitudinal changes in clinically relevant biomarkers of glycemic control with information on baseline disease state, demographics, disease progression, and different therapeutic interventions, either when given alone or as add-on combination therapy. The model was able to simultaneously characterize changes in fasting plasma glucose, fasting serum insulin, and glycated hemoglobin A1c following administration of sulfonylurea, metformin, and thiazolidinedione as well as disease progression in clinical trials ranging from 16-104 weeks of treatment. The mechanistic components of this generalized mechanism-based platform, based on knowledge of pharmacology, insulin-glucose homeostatic feedback, and diabetes pathophysiology, allows its application to be further expanded to other antidiabetic drug classes and combination therapies.
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