We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Development and Qualification of a Drug‐Disease Modeling Platform to Characterize Clinically Relevant Endpoints in Type 2 Diabetes Trials.
- Authors
Hurtado, Felipe K.; Schmidt, Stephan; Gaitonde, Puneet; Garhyan, Parag; Chien, Jenny Y.
- 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.
- Subjects
TYPE 2 diabetes; BLOOD sugar; GLYCEMIC control; DIABETES pathophysiology; HYPOGLYCEMIC agents
- Publication
Clinical Pharmacology & Therapeutics, 2018, Vol 104, Issue 4, p699
- ISSN
0009-9236
- Publication type
Article
- DOI
10.1002/cpt.998