Second Generation Sulfonylurea


Second Generation Sulfonylurea, Glipizide, Glyburide, Glimepiride, Amaryl, Sulfonylurea Drug Interactions Causing Hypoglycemia

  1. Better effect in lean patients
  2. Consider when Hemoglobin A1C <9%
  3. Second-line to Metformin in most patients
  4. Consider as first-line in specific cohorts
    1. Consider when post-prandial Glucose 200 to 300 mg/dl
    2. Consider when Type II with Polyuria, polydipsia
  • Contraindication
  1. Sulfa Allergy (applies to sulonylureas)
  2. Renal and liver dysfunction
    1. Use caution with Sulfonylureas (especially Glyburide)
    2. Repaglinide or Nateglinide may be preferred here
  3. Avoid Glyburide in cardiovascular disease (and in general due to Hypoglycemia risk)
    1. Glimepiride and Glipizide do not appear to increase risk
  • Mechanism
  1. Pancreatic beta cell stimulation for Insulin release
  2. Secretagogues do not burn out the beta cells sooner
  • Dosing
  • Pearls
  1. Use Long acting agents
  2. Increase dose every 1-2 weeks until adequate response
  3. No response in 25-30% of Type II Diabetics
  4. Never combine secretagogues
    1. They all have same site of activity
    2. If one does not work, then all will not work
  • Preparations
  • Glimepiride
  1. Glimepiride (Amaryl)
    1. Start: 1-2 mg orally daily
    2. Usual: 4 mg orally daily
    3. Maximum: 8 mg orally daily (doses above 4 mg daily, are unlikely to offer benefit)
    4. Advantages
      1. More rapid onset with longer duration
      2. Lower Incidence of Hypoglycemia than Glyburide, but greater risk than Glipizide
      3. Preferred of class for Coronary Artery Disease
  • Preparations
  • Glipizide
  1. Glipizide (Glucotrol)
    1. Start: 5 mg orally daily
    2. Usual: 10-20 mg orally daily
    3. Maximum: 20 mg orally twice daily
  2. Glipizide Extended Release (Glucotrol XL)
    1. Start: 5 mg orally daily
    2. Usual: 5-10 mg orally daily
    3. Maximum: 20 mg orally daily (doses above 10 mg daily ER, are unlikely to offer benefit)
    4. Advantages: Least expensive Sulfonylurea
  • Preparations
  • Glyburide
  1. Precautions
    1. Glipizide may be preferred instead due to increased risks of Hypoglycemia associated with Glyburide, Glimepiride
      1. Other agents are generic (no cost advantage to Glyburide)
    2. Glyburide has been associated with worse cardiovascular outcomes in patients presenting for emergent PCI
      1. Jørgensen (2011) Int J Cardiol 152:327-331 [PubMed]
    3. Glyburide appears to predispose to more severe Hypoglycemia than the other Second Generation Sulfonylureas
      1. Glyburide should be avoided in renal dysfunction where GFR <50 mL/min (increases hypglycemia risk)
      2. Glyburide should be avoided in severe hepatic dysfunction (increases Hypoglycemia risk)
      3. Gangji (2007) Diabetes Care 30:389-94 [PubMed]
  2. Glyburide (DiaBeta, Micronase)
    1. Start: 2.5 to 5 mg PO qd
    2. Usual: 5-20 mg PO qd
    3. Maximum: 20 mg PO qd
  3. Glyburide Micronized (Glynase, PresTab)
    1. Start: 1.5 to 3 mg PO qd
    2. Usual: 3-12 mg PO qd
    3. Maximum: 12 mg PO qd
  • Adverse Effects
  1. Weight gain
  2. Hypoglycemia
    1. Higher risk of severe Hypoglycemia with Glyburide than other Sulfonylureas
    2. See Drug Interactions below
  3. Cardiovascular Disease does not appear to be at increased risk with Sulfonylureas
    1. Early studies had suggested possible increased cardiovascular risk
    2. Sulfonylureas appear to be neutral in their cardiovascular risk effects
    3. Contrast with GLP-1 Agonists and SGLT2 Inhibitors which reduce cardiovascular risk
    4. (2019) presc lett 26(12): 71