A Diabetes Outcome Progression Trial (ADOPT)
An international multicenter study of the comparative efficacy of rosiglitazone, glyburide, and metformin in recently diagnosed type 2 diabetes
- Giancarlo Viberti, MD1,
- Steven E. Kahn, MB, CHB2,
- Douglas A. Greene, MD3,
- William H. Herman, MD3,
- Bernard Zinman, MD4,
- Rury R. Holman, MD5,
- Steven M. Haffner, MD6,
- Daniel Levy, MD7,
- John M. Lachin, SCD8,
- Rhona A. Berry, BSC9,
- Mark A. Heise, PHD9,
- Nigel P. Jones, MA9 and
- Martin I. Freed, MD9
- 1Guy’s, King’s, and St. Thomas’ School of Medicine, King’s College, London, U.K.
- 2Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington and Department of Veterans Affairs Puget Sound Health Care System, Seattle, Washington
- 3Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan
- 4Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, Toronto, Canada
- 5Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford, U.K.
- 6University of Texas Health Science Center at San Antonio, San Antonio, Texas
- 7Framingham Heart Study, Framingham, Massachusetts
- 8Biostatistics Center, George Washington University, Rockville, Maryland
- 9GlaxoSmithKline Pharmaceuticals, Collegeville, Philadelphia, Pennsylvania
Abstract
OBJECTIVE—Therapies with metformin, sulfonylureas, or insulin improve glycemic control in the short term but do not prevent progressive islet β-cell failure or long-term deterioration in glycemia. Our goal was to evaluate, in patients recently diagnosed with type 2 diabetes (<3 years), the long-term efficacy of monotherapy with rosiglitazone on glycemic control and on the progression of pathophysiological abnormalities associated with type 2 diabetes as compared with metformin or glyburide monotherapy.
RESEARCH DESIGN AND METHODS—A Diabetes Outcome Progression Trial (ADOPT) is a randomized, double-blind, parallel-group study consisting of a screening visit, a 4-week placebo run-in, a 4-year treatment period, and an observational follow-up of ∼3,600 drug-naïve patients with type 2 diabetes diagnosed within the previous 3 years. After run-in, patients will be randomized to rosiglitazone, glyburide, or metformin titrated to the maximum effective daily doses (8 mg rosiglitazone, 15 mg glyburide, or 2 g metformin). The primary outcome is time to monotherapy failure, defined as the time following titration to the maximal effective or tolerated dose when fasting plasma glucose exceeds 180 mg/dl (10 mmol/l). Secondary outcomes include measures of islet β-cell function, insulin sensitivity, dyslipidemia, changes in urinary albumin excretion, plasminogen activator inhibitor-1 antigen, fibrinogen, and C-reactive protein. Safety and tolerability will also be evaluated. Patient-reported outcomes and resource utilization data will be collected and analyzed.
CONCLUSIONS—ADOPT will provide data on the effect of mechanistically differing treatment options on metabolic control, β-cell function, and markers of macrovascular disease risk in type 2 diabetes.
- ACR, albumin-to-creatinine ratio
- ADA, American Diabetes Association
- ADOPT, A Diabetes Outcome Progression Trial
- AE, adverse event
- CHD, coronary heart disease
- CRP, C-reactive protein
- DSC, Diabetes Symptoms Checklist
- DTSQ, Diabetes Treatment Satisfaction Questionnaire
- FPG, fasting plasma glucose
- HCG, human chorionic gonadotrophin
- HOMA, homeostasis model assessment
- HPI, intact human proinsulin
- hsCRP, highly sensitive CRP
- MRFIT, Multiple Risk Factor Intervention Trial
- OGTT, oral glucose tolerance test
- PAI-1, plasminogen activator inhibitor-1
- PI/IRI, proinsulin-to-immunoreactive insulin ratio
- SF-36, Medical Outcomes Study 36-Item Short-Form Health Survey
- UKPDS, U.K. Prospective Diabetes Study
Footnotes
-
Address correspondence and reprint requests to Giancarlo Viberti, MD, FRCP, Unit of Metabolic Medicine, Division of Medicine, GKT School of Medicine, Floor 5, Thomas Guy House, Guy’s Hospital, London SE1 9RT, U.K. E-mail: giancarlo.viberti{at}kcl.ac.uk.
Received for publication 23 August 2001 and accepted in revised form 8 July 2002.
G.V. and S.E.K. have been members of an advisory panel for, hold stock in, and have received consulting fees and research support from GlaxoSmithKline. W.H.H. has been a member of an advisory panel for and has received consulting fees and grant support from GlaxoSmithKline. B.Z. has received honoraria for speaking engagements as well as consulting fees and grant support from GlaxoSmithKline. R.R.H. and D.L. have received consulting fees from GlaxoSmithKline. S.M.H. has received honoraria for speaking engagements from GlaxoSmithKline. J.M.L. has been a member of an advisory panel for and has received consulting fees from GlaxoSmithKline.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
- DIABETES CARE
