Research and development of Metformin (Glucophage)
Its Clinical Research Center has been involved in the early stages of research on new anti-diabetic medications approved by the FDA for the management of diabetes in the United States and throughout the world. Metformin (Glucophage), the most commonly prescribed drug for the treatment of type 2 diabetes today was introduced and disseminated in the U.S. after results of extensive studies performed by Professor Ralph A. DeFronzo, M.D., Principal Investigator for the US Multicenter Metformin Trials, and Deputy Director of the Texas Diabetes Institute.
DeFronzo RA et al. New England Journal of Medicine 333:541-549, August 31, 1995
Pioneering early treatment and diabetes prevention
Since the early 1990’s seminal investigations conducted at the Texas Diabetes Institute have led the way to the widespread use of numerous safe and efficacious new agents such as Pioglitazone, Byetta, Farxiga, Atorvastatin, Losartan, Nateglinide, novel Insulin Analogs, and many others, in the fight against diabetes and its complications.
- Myazaki Y et al. Diabetes 52:1943-1950, April, 2003
- Belfort R et al. New England Journal of Medicine 355:2297-2307, Nov 3, 2006
- Bajaj M et al. Diabetes 52:1364-1370, June 2003
- Cersosimo E et al. Journal of Clinical Endocrinology and Metabolism 96: 1763-1771, 2011
- DeFronzo RA et al. New England Journal of Medicine 364: 1104-1115, 2011
- Merovci A et al. Journal of Clinical Investigation 124: 509-514, 2014
More recently, Dr. DeFronzo has completed a nationwide trial using pioglitazone and reduced the conversion of prediabetes to diabetes by 72%. The latest trend is to combine newer drugs to address obesity and diabetes with anti-hyperglycemic effects and weight loss. This has been accomplished with the use of Byetta, which have been extensively studied at the Texas Diabetes Institute.
- DeFronzo RA et al. New England J Med 364:1104-1115, March 24, 2011
- DeFronzo RA et al. Diabetes Care 33:951-957, May 2010
Innovation, safety and efficacy of anti-diabetic drugs
The Texas Diabetes Institute Diabetes Research Center has had very active participation in various nationwide clinical trials designed to develop new treatment agents for type 2 and 1 diabetes. In some of these trials the TDI has actually taken the lead and positive and encouraging results have been and continue to be reported in major Journals.
- Fernandez M et al. Diabetes Care 31:101-108, 2008
- Cersosimo E et al. J Clinical Endo and Metabol 96:1763-1770, March 2011
- Triplitt C et al. Vascular Health and Risk Management, July 2010
Implementation of new combination therapies for diabetes
Many clinical trials are intended to identify the best combination therapies for people with diabetes. In this regard the Texas Diabetes Institute has been extremely successful. Many of the results have been presented orally at national and international meetings and papers have been published and continue to be submitted for publications.
- DeFilippis et al. Diabetes Care 29:2371-2377, Nov 2006
- DeFronzo RA et al. Diabetes Care 34:S202-S209, May 2011
Glucose control and avoidance of diabetes complications
Studies conducted at the Texas Diabetes Institute have generated sufficient information to justify safe and aggressive lowering of the blood glucose in patients with diabetes. These clinical investigations essentially provide support for the use of any means, within safety boundaries, to achieve and maintain blood sugar levels within the target range, i.e., below 100-110 mg/dl during fasting and no greater than 160-180 mg/dl after meals. Glucose control is important because for every 1% reduction in mean HbA1c value there is a ~35% reduction in the development and progression of complications, such as heart disease, stroke, kidney failure, eye and peripheral nerve disorders, that may lead to amputations.
Based upon these discoveries at the Texas Diabetes Institute, and in other research institutions, centers around the world have implemented these recommendations.
Avoidance of diabetes complications, such as amputations, blindness and kidney failure, is one very important aspect of our research mission.
- Shulman Gi et al. New England J Med 322:223-228, Jan 25, 1990
- Cersosimo E and DeFronzo RA. Diabetes Metab Res Rev 22:423-436, 2006
- Wajcberg E et al. J Clin Endo Metabol 92:1256-1262, 2007
De-coding the genetics of Type 2 diabetes
A major research mission of the Texas Diabetes Institute is to identify type 2 diabetes genes that contribute to a person's genetic susceptibility to develop the type 2 diabetes mellitus in the Mexican-American Community. In the Hispanic community, if both parents have diabetes, there is a 60-70% chance their children will develop diabetes. If only one parent has diabetes, there is a 30-40% chance that the children will develop diabetes. Lack of physical activity, obesity, and a high fat diet are important contributing factors, which can magnify the genetic tendency and lead to overt diabetes. Unraveling the genetic code that causes type 2 diabetes in Mexican-Americans is the principal aim of a large ongoing study under the leadership of Professor Ralph A. DeFronzo.
- Bajaj M et al. Diabetes 56:743-752, march 2007
- Kashyap S et al. Diabetes 52:2461-2474, Oct 2003
- Coletta DK et al. Diabetes 58:279-284, Jan 2009
- Reyna S et al. Diabetes 57:2595-2602, Oct 2008
(Ralph A. DeFronzo, MD)
- Lily Award, 1987 (ADA)
- Albert Renold Award, 2001 (ADA)
- Novartis Award, 2003 (ADA)
- Banting Medal for Scientific Achievement Award, 2008 (ADA)
- Claude Bernard Award for Scientific Achievement, 2008 (EASD)
- Presidential Award, UTHSCSA, 2009
- Outstanding Clinical Investigator Worldwide, 2012 (CODHy)
- Outstanding Scientific Achievement Award, 2014 (American College of Clinical Nutrition)
After his truly seminal findings regarding the role of insulin resistance in the pathogenesis of type 2 diabetes, Dr. Ralph DeFronzo’s latest quest centers on genetic research, an exciting discovery process that hopefully will lead to a cure for type 2 diabetes mellitus.
In the year 2008 Dr. Ralph DeFronzo was honored by the ADA and EASD simultaneously with the Banting Medal for Scientific Achievement Award (ADA) and the Claude Bernard for Scientific Achievement (EASD). These prestigious awards represent the pinnacle of Dr. DeFronzo’s clinical research career in the field of diabetes. Dr. DeFronzo is a “symbol of excellence” and a true leader and a master for all his clinical and research teammates at the Texas Diabetes Institute.
Reference: DeFronzo RA. Banting Lecture. Diabetes 58:773-795, April 2009