The GRADE Study
Recruitment begins for important new type 2 diabetes study

The Naomi Berrie Diabetes Center is now looking for volunteers to take part in an NIH study to 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. Beginning recruitment in June, the project is called the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness—the (GRADE) Study.

When metformin is not enough to help manage type 2 diabetes,  doctors often add one of several other drugs to the person’s regimen to lower glucose levels. But while short-term studies have shown the efficacy of different drugs when used with metformin, there have been no long-term studies that show which combination works best and has fewer side effects.

“Type 2 diabetes progresses slowly, over a long period of time,” said Barbara Linder, MD, PhD, and the GRADE project officer at the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases. “This study will help us understand how different combinations of medications affect the disease over time and ultimately help physicians make better choices for their patients’ long-term care.”

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 aims to enroll about 5,000 patients. Investigators at the Berrie Center (and 36 other study sites across the country) are seeking people who have been diagnosed with type 2 diabetes within the last five years. Volunteers 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 of the classes of medications increase insulin levels. They are: 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 free of charge through the study, which includes 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,” said David M. Nathan, M.D., of Massachusetts General Hospital, Boston. Dr. Nathan and John Lachin, Sc.D., of The George Washington University, Washington, D.C., are co-principal investigators.

“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 said. “This should provide understanding of how to personalize the treatment of diabetes.

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.

“This is a wonderful opportunity for people with type 2 diabetes to receive all the benefits that clinical trials provide, such as diabetes education and diabetes medicines free of charge for the length of the study,” said the Berrie Center’s, Patricia Kringas, a nurse, a certified diabetes educator and the research coordinator for the new GRADE Study. “Being in a clinical trial can be extremely helpful, because it provides the support for patients to have good diabetes management and live healthy lives.”

If you are interested in participating in the GRADE study contact: Patricia Kringas, RN, MA and research coordinator for the GRADE Study at the Naomi Berrie Diabetes Center: (212) 851-5489 or email mpk40@columbia.edu.