Second Generation Sulfonylurea

Aka: Second Generation Sulfonylurea, Glipizide, Glyburide

1. See Also
   1. First Generation Sulfonylurea
   2. Oral Hypoglycemic Agents
2. Indications: Type II Diabetes Mellitus (early, phase 1-2)
   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
3. 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
      1. Glimepiride and Glipizide do not appear to increase risk
4. Mechanism
   1. Pancreatic beta cell stimulation for Insulin release
   2. Secretagogues do not burn out the beta cells sooner
5. 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
6. Preparations: Glimepiride
   1. Glimepiride (Amaryl)
      1. Start: 1-2 mg PO qd
      2. Usual: 4 mg PO qd
      3. Maximum: 8 mg PO qd
      4. Advantages
         1. More rapid onset with longer duration
         2. Lower Incidence of Hypoglycemia
         3. Preferred of class for Coronary Artery Disease
7. Preparations: Glipizide
   1. Glipizide (Glucotrol)
      1. Start: 5 mg PO qd
      2. Usual: 10-20 mg PO qd
      3. Maximum: 20 mg PO bid
   2. Glipizide Extended Release (Glucotrol XL)
      1. Start: 5 mg PO qd
      2. Usual: 5-10 mg PO qd
      3. Maximum: 20 mg PO qd
      4. Advantages: Least expensive Sulfonylurea
8. Preparations: Glyburide
   1. Precautions
      1. Glipizide and Glimepiride may be preferred instead due to increased risks associated with Glyburide
         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
      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
   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
9. Adverse Effects
   1. Weight gain
   2. Hypoglycemia
      1. Higher risk of severe Hypoglycemia with Glyburide
10. References
    1. Defronzo (1999) Ann Intern Med 131:281-303
    2. Gangji (2007) Diabetes Care 30:389-94
    3. Luna (1999) Prim Care 26:895-915