Medicinal Evolution of Natural Hormones to Transform Drug Treatment of Obesity
Richard DiMarchi, Ph.D.
Distinguished Professor Linda & Jack Gill Chair in Biomolecular Science
Indiana University
Dr. Richard DiMarchi is Distinguished Professor of Chemistry and Gill Chair in Biomolecular Sciences at Indiana University. A member of the National Academy of Medicine and National Inventors Hall of Fame, he previously held leadership roles at Eli Lilly and Novo Nordisk. He contributed to the discovery and development of Humalog®, Glucagon®, and Forteo® and pioneered multimode agonists for diabetes and obesity. Dr. DiMarchi holds more than 100 U.S. patents, has authored over 250 scientific publications, and co-founded six biotechnology companies. In 2026, he was named a recipient of the Broermann Medical Innovation Award for groundbreaking contributions to metabolic research.
Summary
The epidemic of obesity and its associated comorbidities represents a medicinal challenge that warrants broad molecular diversity. In concert with multiple collaborators, my IU laboratory has pioneered the recruitment of endogenous hormones and physiological mechanisms optimized for pharmacological purposes to address the heterogeneity constituted by the multiple diseases associated with the metabolic syndrome. From the earliest demonstration with lispro-insulin to the most recent discovery of single molecule, mixed incretin agonists we have pursued the discovery of chemically optimized macromolecules directed at the successful management of endocrine and related diseases. We have integrated classical small and large molecule-based pharmacology, while advancing the chemical methodology in synthesis of complex macromolecules. The integrated pharmacology of these peptides, proteins and nuclear hormones has provided a library of drug candidates replicated across multiple academic and commercial laboratories, clinical studies and inspired select registered drugs that deliver transformative therapeutic outcomes. The methodological approach to achieving these results may have merit in the search for medicines to treat other complex diseases correlative to advanced age.
Learning Objectives:
- How endogenous hormones and physiological mechanisms can be leveraged to develop pharmacologic therapies for obesity, metabolic syndrome, and related endocrine diseases.
- hHow the chemical optimization of peptides, proteins, and nuclear hormones—including mixed incretin agonists—can enhance therapeutic activity and support the development of novel medicines for complex metabolic disorders.
- How integrated approaches combining molecular design, pharmacology, and translational research can inform the development of therapies for obesity-related comorbidities and other complex diseases associated with aging.
This page was last updated on Wednesday, August 26, 2026