The University of Maryland Medical Center and the Baltimore VA Medical Center, which are affiliated with the University of Maryland School of Medicine, constitute one of the 37 sites across the United States participating in this trial, called the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study. The study is funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health (NIH). Investigators aim to enroll approximately 5,000 people who have been diagnosed with type 2 diabetes within the last five years. University of Maryland researchers expect to enroll 150 people over the next three years.
Kristi D. Silver, M.D.
In type 2 diabetes, the body does not make enough insulin or use it effectively, resulting in high levels of glucose in the blood. Metformin, a drug that reduces the amount of glucose produced by the liver, is the most commonly used first-line medication. If it does not adequately treat the disease, doctors may add one of several other drugs to help control blood sugar levels.
“Type 2 diabetes progresses slowly, over a long period of time, and most people eventually need two medications to control blood glucose levels,” says Kristi D. Silver, M.D., associate professor of medicine at the University of Maryland School of Medicine and principal investigator for the two sites. “The GRADE study will help us understand how these drug combinations impact blood sugars and the disease in general over time.”
Although studies have shown the efficacy of different drugs when used in combination with metformin over short periods of time, there have been no studies to determine which combination works best and has the fewest side effects when taken over long periods of time.
“Ultimately, this information will help physicians make better choices for their patients’ long-term diabetes care,” says Dr. Silver, who is acting director of the University of Maryland Center for Diabetes and Endocrinology at the University of Maryland Medical Center.
E. Albert Reece, M.D., Ph.D., M.B.A., vice president for medical affairs at the University of Maryland and the John Z. and Akiko K. Bowers Distinguished Professor and dean of the University of Maryland School of Medicine, says, “Type 2 diabetes has reached epidemic proportions, affecting approximately 29 million people in the United States — many of whom will require treatment for much of their lives. The need for effective long-term treatment can dramatically affect decisions that physicians make regarding which medications to prescribe. We need to help patients better manage this chronic disease and avoid serious complications, such as kidney damage and heart disease. The GRADE study is a step in the right direction.”
The study will compare drug effects on glucose levels, adverse effects, diabetes complications and quality of life over an average of nearly five years.
To qualify for the study, patients may be on metformin, but not on any other diabetes medication. During the study, all participants will take metformin, along with a second medication randomly assigned from among four classes of medications, all approved for use with metformin by the U.S. Food and Drug Administration.
Three classes of medications used to treat patients with type 2 diabetes increase insulin levels: 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. There is a fourth type of medication, a long-acting insulin, which also is routinely prescribed.
Participants will be followed for up to seven years to evaluate the drugs’ relative effectiveness in achieving good glycemic control and impact on other diabetes-related conditions and overall health.
David M. Nathan, M.D., of Massachusetts General Hospital, and John Lachin, Sc.D., of George Washington University, are leading the national study.
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-Myers Squibb, Novo Nordisk, Merck, BD Medical and Roche Diagnostics. Learn more about the study at https://grade.bsc.gwu.edu.
For information about the trial at the University of Maryland Medical Center and Baltimore VA Medical Center, contact the study coordinator Camille Paul at (410) 706-1724 or firstname.lastname@example.org.
About the University of Maryland School of Medicine
Established in 1807, the University of Maryland School of Medicine is the first public medical school in the United States, and the first to institute a residency-training program. The School of Medicine was the founding school of the University of Maryland and today is an integral part of the 11-campus University System of Maryland. On the University of Maryland’s Baltimore campus, the School of Medicine serves as the anchor for a large academic health center which aims to provide the best medical education, conduct the most innovative biomedical research and provide the best patient care and community service to Maryland and beyond. www.medschool.umaryland.edu.