Abstract
Diabetes is a chronic disease characterized by hyperglycemia resulting from defects in the regulation of glucose and insulin homeostasis. Hyperglycemia, if not well controlled, will progress to more serious complications. Therefore, all available treatments aim to lower blood glucose by various mechanisms of action. Glucose and glycosylated hemoglobin (HbA1c) are well established and readily measurable biomarkers of the disease. The application of model-based approaches to optimize patient therapy and to gain understanding of the physiology of glucose-insulin regulation is widely accepted in the area of diabetes research and development. In this chapter, we attempt to give a brief overview of the disease and the types of drug-disease models that may be applied in various stages of drug development, including references to key publications of drug-disease models. Through simulations, these models are the essential tools to aid the optimization of clinical trials and to learn about the safety and efficacy of new drugs relative to the standards of care and to face the increasing challenges of drug development for the treatment of diabetes.
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Acknowledgments
The authors wish to thank the Editors for the invitation and the opportunity to share our perspectives on the application of model-based approaches to diabetes research and development. We dedicate this manuscript in memory of Dr. Tom Forgue who has been a mentor, friend and colleague. We also wish to acknowledge the contributions of Dr. Bill Ebling for his insights over the years with special thanks to Dr. Tom Hardy for providing medical expertise and critical review of this chapter. The authors are thankful for the many thought-provoking comments and suggestions from colleagues in academia and industry and coworkers at Eli Lilly and Company who are dedicated to finding treatments for diabetes.
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Chien, J.Y., Sinha, V.P. (2011). The Application of Drug-Disease Models in the Development of Anti-Hyperglycemic Agents. In: Kimko, H., Peck, C. (eds) Clinical Trial Simulations. AAPS Advances in the Pharmaceutical Sciences Series, vol 1. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7415-0_9
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