The incidence of type 2 diabetes and its costs to the healthcare system are continuing to rise. Despite the availability of at least five drug classes for the treatment of type 2 diabetes, metformin remains the most widely used first-line pharmacotherapy. As medicine enters the genomic era, there is the opportunity to understand the genetics underlying inter-individual variation in pharmacological responses of metformin to achieve safer, more effective treatment in those who respond, deploy alternative therapies in those who do not, and develop new comparable agents. The goals of this workshop are to review the state of the science on metformin pharmacogenomics, discuss the scientific and clinical hurdles to furthering our knowledge of the variations in patient responses to metformin, and consider how to utilize effectively this increased understanding to improve patient outcomes in both the academic and private sectors. The workshop also will explore how the potential effectiveness of metformin for additional indications such as diabetes and cancer prevention, polycystic ovarian disease, and Alzheimer's disease can both aid and be aided by the understanding of metformin pharmacogenomics.
Jose Florez, Kathleen Giacomini, Alan Shuldiner
Aaron Pawlyk, Catherine McKeon, Myrlene Staten, Arthur Castle
June 7, 2012
Session I: Understanding the Uses and Responses of Metformin
Moderator: Alan Shuldiner, University of Maryland
- 8:00 a.m.
- Welcome and Orientation
- 8:15 a.m.
- Introduction to Metformin and Its Clinical Use
Ronald Goldberg, University of Miami Miller School of Medicine
- 8:45 a.m.
- Where Are We With Metformin PGx and Where Can We Go?
Ewan Pearson, University of Dundee, United Kingdom
- 9:30 a.m.
- Metformin Pharmacogenomics: Ethnicity and Transporter Gene x Gene Interactions
Kathleen Giacomini, University of California, San Francisco
- 10:00 a.m.
- Pharmacometabolomics and Its Integration With Pharmacogenomics
Rima Kaddurah-Daouk, Duke University Medical Center
- 10:30 a.m.
- 10:45 a.m.
- Guided Discussion Panel
Multitudes of Metformin Populations: Type 2 Diabetes (T2D)– Prevention, Treatment, Pediatrics, Cancer, Aging, Alzheimer's Disease, and Polycystic Ovarian Disease
- 10:45 a.m.
- Challenges Outside of T2D: Diabetes Prevention and Gene Variants
Jose Florez, Massachusetts General Hospital
- 11:00 a.m.
- Panel Discussion
Jose Florez, Massachusetts General Hospital (Prevention)
Phil Zeitler, Children's Hospital Colorado (Pediatric)
Corrine Welt, Massachusetts General Hospital (Polycystic Ovary Syndrome)
Pamela Goodwin, Mount Sinai Hospital (Breast Cancer)
- 11:30 a.m.
- Lunch - grab it and come back!
Session II: Models of Collaboration
Moderator: Toni Pollin, University of Maryland School of Medicine
- 12:15 p.m.
- The eMERGING Role of Health-care Systems in Pharmacogenomics
Rex Chisholm, Northwestern University
- 12:35 p.m.
- Pharmacy Benefit Manager-based Pharmacogenomics and Personalized Medicine Approaches
Eric Stanek, Medco Health Solutions, Inc.
- 12:55 p.m.
- Genetic Architecture of Drug Efficacy and Toxicity - Implications For Discovery and Clinical Implementation
Robert Plenge, Harvard Medical School/Brigham and Women's Hospital
Session III: Models of Collaboration
Moderator: Monique Hedderson, Kaiser Permanente Northern California
- 1:10 p.m.
- RIKEN Center for Genomic Medicine and Collaboration With the Pharmacogenomics Research Network
Michiaki Kubo, Center for Genomic Medicine, RIKEN, Japan
- 1:30 p.m.
- PharmGKB: Lessons From Other Pharmacogenomics Efforts
Teri Klein, Stanford University
- 1:50 p.m.
- Toward Personalized Medicine in Diabetes: A View From Pharma
Dawn Waterworth, GlaxoSmithKline
- 2:10 p.m.
- Past, Present, and Future NIH-funded Metformin Trials
David Nathan, Harvard Medical School/Massachusetts General Hospital
- 2:40 p.m.
- Quick Objectives Overview for Breakout Sessions
Aaron Pawlyk, NIDDK
- 2:45 p.m.
Session IV: Breakout sessions
- 3:00 p.m.
- Discussions of key scientific issues and next steps towards understanding the pharmacogenomics of the metformin response:
- Pharmacogenomics to Understand Metformin’s Mechanism and New Drug Target Discovery
Chairs: Jose Florez, Massachusetts General Hospital and Marc Reitman, NIDDK
- Scientific, Informatics, Collaborative, and Logistical Needs for Large-scale Validation of Metformin Pharmacogenomics
Chairs: Kathy Giacomini, University of California, San Francisco and Monique Hedderson, Kaiser Permanente Northern California
- Challenges to Translating Metformin Pharmacogenomics Into the Clinic for Multiple Endpoints and in Diverse Ethnic Backgrounds
Chairs: Alan Shuldiner, University of Maryland and Eric Stanek, Medco Health Solutions, Inc.
- 3:45 p.m.
- Break; Meeting Chairs prepare summary
- 4:00 p.m.
- Presentations of Discussions at Breakouts and Moderated Discussion
Moderators: External Scientific Chairs
- 4:45 p.m.