Miller School/VA Selected as Site for Study of Diabetes Drug Effectiveness

The Miller School and the Miami VA Healthcare System have been selected as a clinical study site for the NIH-funded project Glycemia Reduction Approaches in Diabetes (GRADE): A Comparative Effectiveness Study.

Led by Jennifer B. Marks, M.D., professor of medicine and Section Chief of Endocrinology at the VA, and Hermes Florez, M.D., Ph.D., associate professor of medicine and public health sciences and Interim Director of the Geriatric Research, Education and Clinical Center (GRECC) at the VA, the study will compare the long-term benefits and risks of four widely used diabetes drugs in combination with metformin, the most common medication for treating type 2 diabetes.

“This is an exciting, long-term study that will answer the question of how to intensify treatment in type 2 diabetes after the use of metformin, which is considered first-line treatment,” said Marks, who is the principal investigator at UM. “It is the first head-to-head comparison of four classes of drugs to decide which is the most safe, efficacious, and cost-effective, and which patients will benefit.”

While short-term studies have shown the efficacy of different drugs when used with metformin, there have been no long-term studies examining which combination works best and has fewer side effects.

“There is a significant need for high-quality comparative effectiveness research, not only regarding glycemic control, but also costs and outcomes that matter most to patients — quality of life and the avoidance of morbid and life-limiting complications, especially cardiovascular disease,” said Florez, principal investigator at the VA, who is also Director of the Division of Epidemiology and Interim Chief of the Division of Gerontology and Geriatric Medicine at the Miller School. “Recently published data from the American Diabetes Association suggest that the cost of diabetes has risen to $245 billion per year, and the growth in cost of anti-diabetic medications is one of the main contributing factors.”

GRADE aims to enroll up to 5,000 patients to study drug effects on glucose levels, side effects, diabetes complications and quality of life over an average of five years.

Investigators at the Miller School and VA are enrolling people diagnosed with type 2 diabetes within the last five years, who 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 FDA-approved medications.

Three of the classes of medications 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. The fourth type of medication is long-acting insulin.

Through the study, participants will receive free diabetes medications and at least four medical visits per year.

Other key members of the Miami GRADE team are Lisset Oropesa, M.D., senior research associate in the Department of Public Health Sciences, and Miriam Gutt, Ph.D., research assistant professor of medicine, who serve as study coordinators at the VA and UM, respectively.

“The GRADE study will be a pioneer in addressing one of the major challenges in diabetes treatment — which combination therapy to choose from the vast array of glucose lowering medications after initial treatment with the No. 1 drug, metformin, is not sufficient,” said Gutt. “It will be very exciting to discern which combination therapies work better and on which individuals, and ultimately be able to individualize treatment.”

GRADE ( 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.

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