Table 1—

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.