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
  • Contraindications
  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 most Sulfonylureas when GFR <60 ml/min (higher risk of Hypoglycemia)
      1. Glipizide Half-Life is not impacted by lower GFR and is safer to use in low GFR
  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. Sulfonylureas stimulate Potassium channel closure on pancreatic beta cell surface
    1. Triggers 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
  • Medications
  • Glimepiride
  1. Glimepiride (Amaryl)
    1. Start: 1-2 mg orally daily taken orally with breakfast
    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. Risk of Hypoglycemia increases with lower GFR
      4. Preferred of class for Coronary Artery Disease
  • Medications
  • 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 taken 30 minutes before breakfast
    2. Usual: 5-10 mg orally daily
    3. Maximum: 20 mg orally daily
      1. Doses above 10 mg daily ER, are unlikely to offer benefit (divide twice daily if used)
    4. Advantages: Least expensive Sulfonylurea
    5. Disadvantages: Extended release may increase Hypoglycemia risk when compared with immediate release
  • Medications
  • 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. Avoid in older adults
      2. Glyburide should be avoided in renal dysfunction where GFR <50-60 mL/min (increases hypglycemia risk)
      3. Glyburide should be avoided in severe hepatic dysfunction (increases Hypoglycemia risk)
      4. Gangji (2007) Diabetes Care 30:389-94 [PubMed]
  2. Glyburide (DiaBeta, Micronase)
    1. Start: 2.5 to 5 mg orally daily with breakfast
    2. Usual: 5-20 mg orally daily
    3. Maximum: 20 mg orally daily
  3. Glyburide Micronized (Glynase, PresTab)
    1. Start: 1.5 to 3 mg orally daily with breakfast
    2. Usual: 3-12 mg orally daily
    3. Maximum: 12 mg orally daily
  • Adverse Effects
  1. Weight gain
  2. Hypoglycemia
    1. Higher risk of severe Hypoglycemia with Glyburide than other Sulfonylureas
    2. Hypoglycemia risk increases with lower GFR
    3. See Drug Interactions below for concurrent agents that increase Hypoglycemia risk
  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
  • Efficacy
  1. Lower Hemoglobin A1C 0.8 to 1.5%
  2. Do not affect all-cause mortality