The longer-term effectiveness of pharmaceuticals to treat type 2 diabetes (T2D) beyond 6-12 months is unknown. GRADE will compare the effectiveness of the 4 most commonly used therapies over 4 to 7 years in 5047 participants with T2D for up to 10 years and treated with metformin alone. Participants were randomly assigned to receive metformin plus either the sulfonylurea glimepiride, the DPP-4 inhibitor sitagliptin, the incretin liraglutide or the basal insulin glargine. The goal is to determine which combination of diabetes medications achieves best glycemic control, has the fewest side effects, and is most beneficial for overall good health.
PRINCIPAL INVESTIGATOR(S)
ADDITIONAL INVESTIGATOR(S)
RESEARCH STAFF
Anna Murphy, CJ Buys, Colleen Suratt, Grace Nogan, Ionut Bebu, Joel Bethepu, Laura Lucs, Liz Legowski, Loree Lamour, Michael Backman, Michaela Gramzinski, Naji Younes, Naureen Elahi, Nisha Grover, Sandy Coppage, Stephanie Hall, Yuping Gao
MAJOR PUBLICATIONS
Nathan, David M., John B. Buse, Steven E. Kahn, Heidi Krause-Steinrauf, Mary E. Larkin, Myrlene Staten, Deborah Wexler, and John M. Lachin. "Rationale and Design of the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE)." Diabetes Care, 2013 Aug;36(8):2254-61. PMCID: PMC3714493
Devchand R, Nicols C, Gallivan JM, Tiktin M, Krause-Steinrauf H, Larkin M, Tuncer DM, GRADE Research Group. Assessment of a National Diabetes Education Program diabetes management booklet: The GRADE experience. Journal Of The American Association Of Nurse Practitioners, 2017;29(5):255-263.
Lachin John M. Fallacies of last observation carried forward analyses. Clinical Trials, 2016;13(2):161-168.
Lachin John M, Bebu Ionut. Application of the Wei–Lachin multivariate one-directional test to multiple event-time outcomes. Clinical Trials, 2015;12(6):627-633.
ADDITIONAL PUBLICATIONS
Learn more at ClinicalTrials.org
GRADE is a clinical trial comparing the effectiveness of 4 alternate randomly-assigned glucose-lowering therapies, in addition to metformin, in 5047 participants with type 2 diabetes over 4-7 years of follow-up to assess metabolic status, side effects, quality of life, beta cell function and micro- and macro-vascular complications.
GRADE will provide high quality evidence to guide physician decisions on the therapeutic assignments to the millions of patients with early (up to 10 years) of type 2 diabetes based on indices of effectiveness and safety over up to 7 years of treatment and follow-up. The principal outcomes to be assessed include the overall metabolic status and the durability of treatment to maintain adequate glycemic control, the evolution and progression of microvascular complications of diabetes that affect eyes, kidneys and nerves and of overt cardiovascular disease (myocardial infarction, stroke and congestive heart failure), and possibly mortality. The study will also assess the incidence of potential adverse effects, especially hypoglycemia and potentially pancreatitis and cancer. The study will also assess heterogeneity of outcomes in specific sub-populations defined by demographics (age, sex), diabetes factors (duration of T2D, family history) and various risk factors to provide patient-specific recommendations, so-called precision medicine.