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
    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 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

VII. 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

VIII. 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 [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

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Cost: Medications

GLIPIZIDE (on 2/19/2015 at Target.com)
GLIPIZIDE 10 MG* Tablet #90 for $10.00 $0.11 each
GLIPIZIDE 5 MG Tablet #90 for $10.00 $0.11 each
GLYBURIDE (on 2/19/2015 at Target.com)
GLYBURIDE 2.5 MG Tablet #90 for $10.00 $0.11 each
GLYBURIDE 5 MG Tablet #90 for $10.00 $0.11 each
GLIMEPIRIDE (on 2/19/2015 at Target.com)
GLIMEPIRIDE 1 MG Tablet #90 for $10.00 $0.11 each
GLIMEPIRIDE 2 MG Tablet #90 for $10.00 $0.11 each
GLIMEPIRIDE 4 MG Tablet #90 for $10.00 $0.11 each
glipizide (on 8/17/2016 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 $0.28 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 $0.28 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 $0.50 each
GLIPIZIDE-METFORMIN 2.5-500 MG Generic $0.62 each
GLIPIZIDE-METFORMIN 5-500 MG Generic $0.50 each
glyburide (on 8/17/2016 at Medicaid.Gov Survey of pharmacy drug pricing)
GLYBURIDE 1.25 MG TABLET Generic $0.12 each
GLYBURIDE 2.5 MG TABLET Generic $0.13 each
GLYBURIDE 5 MG TABLET Generic $0.17 each
GLYBURIDE MICRO 1.5 MG TAB Generic $0.05 each
GLYBURIDE MICRO 3 MG TABLET Generic $0.11 each
GLYBURIDE MICRO 6 MG TABLET Generic $0.21 each
GLYBURIDE-METFORMIN 1.25 MG-250 MG TABLET Generic $0.08 each
GLYBURIDE-METFORMIN 2.5-500 MG Generic $0.08 each
GLYBURIDE-METFORMIN 5-500 MG Generic $0.08 each
glimepiride (on 8/17/2016 at Medicaid.Gov Survey of pharmacy drug pricing)
GLIMEPIRIDE 1 MG TABLET Generic $0.08 each
GLIMEPIRIDE 2 MG TABLET Generic $0.12 each
GLIMEPIRIDE 4 MG TABLET Generic $0.17 each
amaryl (on 4/1/2016 at Medicaid.Gov Survey of pharmacy drug pricing)
AMARYL 2 MG TABLET Generic $0.12 each
AMARYL 4 MG TABLET Generic $0.17 each

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

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

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

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

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