The University of Minnesota and Park Nicollet International Diabetes Center are looking for volunteers to take part in a 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 (GRADE) Study.
If metformin is not enough to help manage type 2 diabetes, a person’s doctor may add one of several other drugs to lower glucose (blood sugar). But while short-term studies have shown the efficacy of different drugs when used with metformin, there have been no long-term studies of which combination works best and has fewer side effects.
“While metformin is the standard first-line medication for diabetes, it has not been as clear which second-line medication is most effective with metformin,” said John Misa, M.D., Chief of Primary Care, Park Nicollet Clinic, and co-investigator at the site. “Through this large, long-term study, we will learn which medications work best with metformin, improving our care for all patients with type 2 diabetes.”
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 nationally. Investigators at the Minnesota-based study sites and 35 other sites across the nation are seeking people diagnosed with type 2 diabetes within the last five years. They 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, including at least four medical visits per year, but will receive other health care through their own providers.
“Type 2 diabetes is a progressive disease and over time effective therapy usually requires the use of more than one medication,” said Elizabeth Seaquist, M.D., Professor of Medicine, University of Minnesota, and Principal Investigator of the University of Minnesota clinical site. “In clinical practice, patients and their care givers have many options for treatment but have no evidence to tell them which combinations work best together. GRADE will provide this evidence, and simplify the choices patients and their care givers must make in everyday practice.”
David M. Nathan, M.D., of Massachusetts General Hospital, Boston and John Lachin, Sc.D., of The George Washington University, Washington, D.C., are co-principal investigators. Barbara Linder, M.D., Ph.D., of the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health, is the project officer for GRADE.