Second Generation Sulfonylurea

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

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 6/18/2017 at Walmart.com)
Glipizide 10mg #60 tablets for $4.00 $0.07 each
Glipizide 10mg #180 tablets for $10.00 $0.06 each
Glipizide 5mg #30 tablets for $4.00 $0.13 each
Glipizide 5mg #90 tablets for $10.00 $0.11 each
Glyburide (on 6/18/2017 at Walmart.com)
Glyburide 2.5mg #30 tablets for $4.00 $0.13 each
Glyburide 2.5mg #90 tablets for $10.00 $0.11 each
Glyburide 5mg (blue) #30 tablets for $4.00 $0.13 each
Glyburide 5mg (blue) #90 tablets for $10.00 $0.11 each
Glyburide 5mg (green) #30 tablets for $4.00 $0.13 each
Glyburide 5mg (green) #90 tablets for $10.00 $0.11 each
Glyburide, micronized (on 6/18/2017 at Walmart.com)
Glyburide, micronized 3mg #30 tablets for $4.00 $0.13 each
Glyburide, micronized 3mg #90 tablets for $10.00 $0.11 each
Glyburide, micronized 6mg #30 tablets for $4.00 $0.13 each
Glyburide, micronized 6mg #90 tablets for $10.00 $0.11 each
Glimepiride (on 6/18/2017 at Walmart.com)
Glimepiride 1mg #30 tablets for $4.00 $0.13 each
Glimepiride 1mg #90 tablets for $10.00 $0.11 each
Glimepiride 2mg #30 tablets for $4.00 $0.13 each
Glimepiride 2mg #90 tablets for $10.00 $0.11 each
Glimepiride 4mg #30 tablets for $4.00 $0.13 each
Glimepiride 4mg #90 tablets for $10.00 $0.11 each
glipizide (on 3/22/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
GLIPIZIDE 10 MG TABLET Generic $0.04 each
GLIPIZIDE 5 MG TABLET Generic $0.03 each
GLIPIZIDE ER 10 MG TABLET Generic $0.27 each
GLIPIZIDE ER 2.5 MG TABLET Generic $0.20 each
GLIPIZIDE ER 5 MG TABLET Generic $0.15 each
GLIPIZIDE XL 10 MG TABLET Generic $0.27 each
GLIPIZIDE XL 2.5 MG TABLET Generic $0.20 each
GLIPIZIDE XL 5 MG TABLET Generic $0.15 each
GLIPIZIDE-METFORMIN 2.5-250 MG Generic $0.44 each
GLIPIZIDE-METFORMIN 2.5-500 MG Generic $0.46 each
GLIPIZIDE-METFORMIN 5-500 MG Generic $0.43 each
glyburide (on 5/17/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
GLYBURIDE 1.25 MG TABLET Generic $0.11 each
GLYBURIDE 2.5 MG TABLET Generic $0.11 each
GLYBURIDE 5 MG TABLET Generic $0.13 each
GLYBURIDE MICRO 3 MG TABLET Generic $0.06 each
GLYBURIDE MICRO 6 MG TABLET Generic $0.16 each
GLYBURIDE-METFORMIN 1.25 MG-250 MG TABLET Generic $0.06 each
GLYBURIDE-METFORMIN 2.5-500 MG Generic $0.06 each
GLYBURIDE-METFORMIN 5-500 MG Generic $0.06 each
glimepiride (on 5/17/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
GLIMEPIRIDE 1 MG TABLET Generic $0.05 each
GLIMEPIRIDE 2 MG TABLET Generic $0.07 each
GLIMEPIRIDE 4 MG TABLET Generic $0.10 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.

Ontology: Glyburide (C0017628)

Definition (NCI) A highly protein bound, longer-acting second-generation sulfonylurea with antihyperglycemic activity. Glyburide, also called glibenclamide, is more likely to cause hypoglycemic episodes due to its longer half-life and possible displacement by other highly protein bound drugs. This agent is metabolized into two inactive metabolites which are excreted in the bile and urine. This agent shows peroxisome proliferator-activated receptor gamma (PPARgamma) agonistic activity.
Definition (MSH) An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide.
Definition (CSP) N-4-beta-(2-methoxy-5-chlorobenzamido) -ethylbenzosulfonyl-N'- cyclohexylurea; hypoglycemic used against non-insulin dependent diabetes mellitus; thought to act by increasing insulin receptor expression in target tissues.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D005905
SnomedCT 384978002, 80870001, 387466004
LNC LP14720-4, MTHU001812
English Glibenclamide, Glybenclamide, Benzamide, 5-chloro-N-(2-(4-((((cyclohexylamino)carbonyl)amino)sulfonyl)phenyl)ethyl)-2-methoxy-, glyburide, Glyburide, Gyburide, Glyburide (substance), glyburide (medication), GLYBURIDE, Glyburide [Chemical/Ingredient], glybenclamide, glyBURIDE, glibenclamide, Glybenzcyclamide, Glyburide (product), Glibenclamide (substance), GlyBURIDE
Swedish Glyburid
Czech glibenklamid
Finnish Glyburidi
German Glyburid, Glibenclamid, Glybencylamid
Russian GLIBURID, GLIBENKLAMID, ГЛИБЕНКЛАМИД, ГЛИБУРИД
Croatian GLIBURID
Polish Euclamin, Glyburide, Glibenklamid
Japanese グリベンクラミド, グリブリド
Spanish gliburida (sustancia), glibenclamida (producto), glibenclamida (sustancia), glibenclamida, glibenzciclamida, gliburida, Glibenclamida, Gliburida
French Glibenclamide
Italian Gliburide
Portuguese Glibenclamida, Glibureto
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Glipizide (C0017642)

Definition (NCI) A short-acting, second-generation sulfonylurea with hypoglycemic activity. Glipizide is rapidly absorbed, has a very quick onset of action and a short half-life. This agent is extensively metabolized in the liver and the metabolites as well as the unchanged form are excreted in the urine.
Definition (MSH) An oral hypoglycemic agent which is rapidly absorbed and completely metabolized.
Definition (CSP) 1-cyclohexyl-3-(p-(2-(5-methyl pyrazinecarboxamido) ethyl) phenyl) sulfonylurea; a typical member of the sulfonylurea family of type II (NIDDM) antidiabetic drugs.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D005913
SnomedCT 26124005, 387143009
LNC LP14719-6, MTHU001811
English Glidiazinamide, Glipizide, Glydiazinamide, Glypidizine, Pyrazinecarboxamide, N-(2-(4-((((cyclohexylamino)carbonyl)amino)sulfonyl)phenyl)ethyl)-5-methyl-, glipizide, GLIPIZIDE, glipizide (medication), Glipizide [Chemical/Ingredient], glipiZIDE, Glipizide product, Glipizide (product), Glipizide (substance), GlipiZIDE
Swedish Glipizid
Czech glipizid
Finnish Glipitsidi
Russian GLIPIZID, ГЛИПИЗИД
Japanese グリピジジン, グリジアジンアミド, グリピジド
Polish Glipizyd
Spanish glidiacinamida, glidiazinamida, glipicida (sustancia), glipicida, glipizida (producto), glipizida (sustancia), glipizida, Glidiacinamida, Glipidicina, Glipizida
French Glipizide
German Glidiazinamid, Glipizidum, Glipizid, Glydiazinamid, Glypidizin
Italian Glipizide
Portuguese Glidiazinamida, Glipidizina, Glipizida
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: glimepiride (C0061323)

Definition (NCI) A long-acting, third-generation sulfonylurea with hypoglycemic activity. Compared to other generations of sulfonylurea compounds, glimepiride is very potent and has a longer duration of action. This agent is metabolized by CYP2C9 and shows peroxisome proliferator-activated receptor gamma (PPARgamma) agonistic activity.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C057619
SnomedCT 109079009, 386966003
LNC LP35577-3, MTHU018302
English 1-(4-(2-(3-ethyl-4-methyl-2-oxo-3-pyrrolinecarboxamido)ethyl)phenylsulfonyl)-3-(4-methylcyclohexyl)urea, glimepiride, glimepiride (medication), glymepiride, GLIMEPIRIDE, glimepiride [Chemical/Ingredient], Glimepiride, Glimepiride (product), Glimepiride (substance)
Spanish glimepirida (producto), glimepirida (sustancia), glimepirida
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Amaryl (C0595112)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C057619
English Amaryl, amaryl, Amarel, Aventis Behring brand of glimepiride, Aventis Pharma brand of glimepiride, Aventis brand of glimepiride, Hoechst brand of glimepiride
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Second generation sulfonylurea (C1300198)

Concepts Organic Chemical (T109) , Pharmacologic Substance (T121)
SnomedCT 386050002
English Second generation sulfonylurea (product), Second generation sulfonylurea, Second generation sulphonylurea
Spanish sulfonilurea de segunda generación (producto), sulfonilurea de segunda generación
Derived from the NIH UMLS (Unified Medical Language System)

Related Topics in Pharmacology

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