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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. 1Diabetes Center, Massachusetts General Hospital, Boston, Massachusetts
  2. 2University of North Carolina School of Medicine, Chapel Hill, North Carolina
  3. 3Clinical Center for Research Excellence, Charles R. Drew University, Los Angeles, California
  4. 4Department of Internal Medicine, University of Pisa, Pisa, Italy
  5. 5Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford University, Oxford, U.K.
  6. 6Department of Internal Medicine and Yale Center for Clinical Investigation, Yale University School of Medicine, New Haven, Connecticut
  7. 7Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
  1. Corresponding author: David. M. Nathan, dnathan{at}partners.org
Diabetes Care 2009 Jan; 32(1): 193-203. https://doi.org/10.2337/dc08-9025
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    Initiation and adjustment of insulin regimens. Insulin regimens should be designed taking lifestyle and meal schedule into account. The algorithm can only provide basic guidelines for initiation and adjustment of insulin. See reference 90 for more detailed instructions. aPremixed insulins not recommended during adjustment of doses; however, they can be used conveniently, usually before breakfast and/or dinner, if proportion of rapid- and intermediate-acting insulins is similar to the fixed proportions available. bg, blood glucose.

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    Figure 2—

    Algorithm for the metabolic management of type 2 diabetes; Reinforce lifestyle interventions at every visit and check A1C every 3 months until A1C is <7% and then at least every 6 months. The interventions should be changed if A1C is ≥7%. aSulfonylureas other than glybenclamide (glyburide) or chlorpropamide. bInsufficient clinical use to be confident regarding safety. See text box, entitled titration of metformin. See Fig. 1 for initiation and adjustment of insulin. CHF, congestive heart failure.

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    Summary of glucose-lowering interventions

    InterventionExpected decrease in A1C with monotherapy (%)AdvantagesDisadvantages
    Tier 1: well-validated core
        Step 1: initial therapy
            Lifestyle to decrease weight and increase activity1.0–2.0Broad benefitsInsufficient for most within first year
            Metformin1.0–2.0Weight neutralGI side effects, contraindicated with renal insufficiency
        Step 2: additional therapy
            Insulin1.5–3.5No dose limit, rapidly effective, improved lipid profileOne to four injections daily, monitoring, weight gain, hypoglycemia, analogues are expensive
            Sulfonylurea1.0–2.0Rapidly effectiveWeight gain, hypoglycemia (especially with glibenclamide or chlorpropamide)
    Tier 2: less well validated
        TZDs0.5–1.4Improved lipid profile (pioglitazone), potential decrease in MI (pioglitazone)Fluid retention, CHF, weight gain, bone fractures, expensive, potential increase in MI (rosiglitazone)
        GLP-1 agonist0.5–1.0Weight lossTwo injections daily, frequent GI side effects, long-term safety not established, expensive
    Other therapy
        α-Glucosidase inhibitor0.5–0.8Weight neutralFrequent GI side effects, three times/day dosing, expensive
        Glinide0.5–1.5aRapidly effectiveWeight gain, three times/day dosing, hypoglycemia, expensive
        Pramlintide0.5–1.0Weight lossThree injections daily, frequent GI side effects, long-term safety not established, expensive
        DPP-4 inhibitor0.5–0.8Weight neutralLong-term safety not established, expensive
    • ↵a Repaglinide more effective in lowering A1C than nateglinide. CHF, congestive heart failure; GI, gastrointestinal; MI, myocardial infarction.

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Diabetes Care: 32 (1)

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January 2009, 32(1)
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Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy
David M. Nathan, John B. Buse, Mayer B. Davidson, Ele Ferrannini, Rury R. Holman, Robert Sherwin, Bernard Zinman
Diabetes Care Jan 2009, 32 (1) 193-203; DOI: 10.2337/dc08-9025

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Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy
David M. Nathan, John B. Buse, Mayer B. Davidson, Ele Ferrannini, Rury R. Holman, Robert Sherwin, Bernard Zinman
Diabetes Care Jan 2009, 32 (1) 193-203; DOI: 10.2337/dc08-9025
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