The Baylor Endocrine Center at Dallas is seeking volunteers to participate in a study that will compare the long-term benefits and risks of four widely used diabetes drugs in combination with metformin, the most common first-line medication for treating type 2 diabetes.
The project, entitled “The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study” (GRADE), is being funded by the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health (NIH).
The GRADE Web page notes that Type 2 diabetes is an epidemic that is threatening to become the century’s major public health problem and poses enormous human and economic challenges worldwide. Most people with diabetes will eventually need two medications to control blood glucose levels, and a major challenge is to determine which of the several possible medications is the best choice for people who are already being treated with metformin, the most commonly used diabetes drug. However, when metformin is not enough to help manage type 2 diabetes, the patient’s doctor may add one of several other drugs to lower blood sugar. While short-term studies have shown the effectiveness of different drugs when used with metformin, there have been no long-term studies. Consequently, the purpose of the GRADE study is to determine which combination of two medications works best for glycemic control, has the fewest side effects, and is the most beneficial for overall health. The study will compare drug effects on glucose levels, adverse effects, diabetes complications and quality of life over an average of nearly five years.
GRADE’s objective is to enroll some 5,000 patients around the country, and investigators at Baylor Endocrine Center and at 36 other study sites are seeking individuals who have been diagnosed with type 2 diabetes within the past five years. Study subjects may be currently taking metformin, but no other diabetes medications. During the study, all participants will take metformin along with a second medication randomly assigned from among four classes of medications approved for use with metformin by the U.S. Food and Drug Administration. Three of the classes of medications increase insulin levels, namely: sulfonylurea, which increases insulin levels directly; DPP-4 inhibitor, which indirectly increases insulin levels by increasing the effect of a naturally occurring intestinal hormone; and GLP-1 agonist, which increases the amount of insulin released in response to nutrients. The fourth type of medication is a long-acting insulin. Participants will have their diabetes medications managed through the study free of charge, including at least four medical visits per year, but will receive other health care through their own providers.
“What differentiates GRADE from previous studies is that it will perform a head-to-head, comprehensive comparison of the most commonly used drugs over a long period of time,” explains Dr. David M. Nathan, MD, of Massachusetts General Hospital, Boston in a Baylor release. Dr. Nathan and Dr. John Lachin, ScD, of The George Washington University, Washington, D.C., are co-principal investigators for the GRADE study nationally.
“In addition to determining which medications control blood glucose levels most effectively over time, we hope to examine individual factors that are associated with better or worse response to the different medications,” Dr. Nathan adds. “This should provide understanding of how to personalize the treatment of diabetes.”
Dr. Barbara Linder, MD, PhD, of the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health, is the project officer for GRADE.
GRADE (ClinicalTrials.gov number: NCT01794143) is supported under NIH grant U01DK098246. Additional support in the form of donation of supplies comes from the National Diabetes Education Program, Sanofi-Aventis, Bristol-Meyers Squibb, Novo Nordisk, Merck, BD Medical and Roche Diagnostics.
Learn more about the study at
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