Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy

A consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes

  1. David M. Nathan, MD1,
  2. John B. Buse, MD, PhD2,
  3. Mayer B. Davidson, MD3,
  4. Ele Ferrannini, MD4,
  5. Rury R. Holman, FRCP5,
  6. Robert Sherwin, MD6 and
  7. Bernard Zinman, MD7
  1. 1From the Diabetes Center, Massachusetts General Hospital,
    Boston, Massachusetts
  2. 2From the University of North Carolina School of Medicine,
    Chapel Hill, North Carolina
  3. 3From the Clinical Center for Research Excellence, Charles R. Drew University,
    Los Angeles, California
  4. 4From the Department of Internal Medicine, University of Pisa,
    , Italy
  5. 5From the Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford University,
    , U.K.
  6. 6From the Department of Internal Medicine and Yale Center for Clinical Investigation, Yale University School of Medicine,
    New Haven, Connecticut
  7. 7From the Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto,
    Toronto, Ontario
    , Canada
  1. Corresponding author: David. M. Nathan, dnathan{at}

The epidemic of type 2 diabetes and the recognition that achieving specific glycemic goals can substantially reduce morbidity have made the effective treatment of hyperglycemia a top priority.1-3 While the management of hyperglycemia, the hallmark metabolic abnormality associated with type 2 diabetes, has historically taken center stage in the treatment of diabetes, therapies directed at other coincident features, such as dyslipidemia, hypertension, hypercoagulability, obesity, and insulin resistance, have also been a major focus of research and therapy. Maintaining glycemic levels as close to the nondiabetic range as possible has been demonstrated to have a powerful beneficial effect on diabetes-specific microvascular complications, including retinopathy, nephropathy, and neuropathy, in the setting of type 1 diabetes;4,5 in type 2 diabetes, more intensive treatment strategies have likewise been demonstrated to reduce microvascular complications.6-8 Intensive glycemic management resulting in lower A1C levels has also been shown to have a beneficial effect on cardiovascular disease (CVD) complications in type 1 diabetes;9,10 however, current studies have failed to demonstrate a beneficial effect of intensive diabetes therapy on CVD in type 2 diabetes.11-13

The development of new classes of blood glucose-lowering medications to supplement the older therapies, such as lifestyle-directed interventions, insulin, sulfonylureas, and metformin, has increased the number of treatment options available for type 2 diabetes. Whether used alone or in combination with other blood glucose-lowering interventions, the increased number of choices available to practitioners and patients has heightened uncertainty regarding the most appropriate means of treating this widespread disease.14 Although numerous reviews on the management of type 2 diabetes have been published in recent years,15-17 practitioners are often left without a clear pathway of therapy to follow. We developed the following consensus approach to the management …

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