Second Generation Sulfonylurea

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

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II. 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

III. 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

IV. Mechanism

  1. Pancreatic beta cell stimulation for Insulin release
  2. Secretagogues do not burn out the beta cells sooner

V. 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

VI. 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

VII. 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

VIII. 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

IX. 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

X. Drug-interactions: Increased risk of Hypoglycemia with Sulfonylureas

  1. Chloramphenicol
  2. Clarithromycin
  3. Fibrates
  4. Fluconazole
  5. Fluoroquinolones (esp. Gatifloxacin)
  6. H2 Receptor Antagonists
  7. Miconazole
  8. Phenylbutazone
  9. Sulfonamide
  10. Verapamil
  11. References
    1. Kabbara (2015) Ther Clin Risk Manag 11: 639–647 [PubMed]
    2. May (2016) Ther Adv Endocrinol Metab 7(2): 69–83 [PubMed]

XI. References

  1. (2017) Presc Lett 25(1): 1-2
  2. Defronzo (1999) Ann Intern Med 131:281-303 [PubMed]
  3. Gangji (2007) Diabetes Care 30:389-94 [PubMed]
  4. Luna (1999) Prim Care 26:895-915 [PubMed]

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Related Studies

Cost: Medications

glipizide (on 10/19/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
GLIPIZIDE 10 MG TABLET Generic $0.05 each
GLIPIZIDE 5 MG TABLET Generic $0.03 each
GLIPIZIDE ER 10 MG TABLET Generic $0.17 each
GLIPIZIDE ER 2.5 MG TABLET Generic $0.14 each
GLIPIZIDE ER 5 MG TABLET Generic $0.11 each
GLIPIZIDE XL 10 MG TABLET Generic $0.17 each
GLIPIZIDE XL 2.5 MG TABLET Generic $0.14 each
GLIPIZIDE XL 5 MG TABLET Generic $0.11 each
GLIPIZIDE-METFORMIN 2.5-250 MG Generic $0.29 each
GLIPIZIDE-METFORMIN 2.5-500 MG Generic $0.26 each
GLIPIZIDE-METFORMIN 5-500 MG Generic $0.27 each
glyburide (on 11/23/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
GLYBURIDE 1.25 MG TABLET Generic $0.07 each
GLYBURIDE 2.5 MG TABLET Generic $0.09 each
GLYBURIDE 5 MG TABLET Generic $0.06 each
GLYBURIDE MICRO 6 MG TABLET Generic $0.20 each
GLYBURIDE-METFORMIN 2.5-500 MG Generic $0.04 each
GLYBURIDE-METFORMIN 5-500 MG Generic $0.05 each
glimepiride (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
GLIMEPIRIDE 1 MG TABLET Generic $0.04 each
GLIMEPIRIDE 2 MG TABLET Generic $0.04 each
GLIMEPIRIDE 4 MG TABLET Generic $0.04 each
FPNotebook does not benefit financially from showing this medication data or their pharmacy links. This information is provided only to help medical providers and their patients see relative costs. Insurance plans negotiate lower medication prices with suppliers. Prices shown here are out of pocket, non-negotiated rates. See Needy Meds for financial assistance information. GoodRx is another tool for finding lower drug prices.

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