II. Indications: Type II Diabetes Mellitus (early, phase 1-2)
- Better effect in lean patients
- Consider when Hemoglobin A1C <9%
- Second-line to Metformin in most patients
- Consider as first-line in specific cohorts
III. Contraindications
- Sulfa Allergy (applies to Sulfonylureas)
- Renal and liver dysfunction
- Use caution with Sulfonylureas (especially Glyburide)
- Repaglinide or Nateglinide may be preferred here
- Avoid most Sulfonylureas when GFR <60 ml/min (higher risk of Hypoglycemia)
- Avoid Glyburide in cardiovascular disease (and in general due to Hypoglycemia risk)
- Glimepiride and Glipizide do not appear to increase risk
IV. Mechanism
V. Dosing: Pearls
- Use Long acting agents
- Increase dose every 1-2 weeks until adequate response
- No response in 25-30% of Type II Diabetics
- Never combine secretagogues
- They all have same site of activity
- If one does not work, then all will not work
VI. Medications: Glimepiride
-
Glimepiride (Amaryl)
- Start: 1-2 mg orally daily taken orally with breakfast
- Usual: 4 mg orally daily
- Maximum: 8 mg orally daily (doses above 4 mg daily, are unlikely to offer benefit)
- Advantages
- More rapid onset with longer duration
- Lower Incidence of Hypoglycemia than Glyburide, but greater risk than Glipizide
- Risk of Hypoglycemia increases with lower GFR
- Preferred of class for Coronary Artery Disease
VII. Medications: Glipizide
-
Glipizide (Glucotrol)
- Start: 5 mg orally daily
- Usual: 10-20 mg orally daily
- Maximum: 20 mg orally twice daily
-
Glipizide Extended Release (Glucotrol XL)
- Start: 5 mg orally daily taken 30 minutes before breakfast
- Usual: 5-10 mg orally daily
- Maximum: 20 mg orally daily
- Doses above 10 mg daily ER, are unlikely to offer benefit (divide twice daily if used)
- Advantages: Least expensive Sulfonylurea
- Disadvantages: Extended release may increase Hypoglycemia risk when compared with immediate release
VIII. Medications: Glyburide
- Precautions
- Glipizide may be preferred instead due to increased risks of Hypoglycemia associated with Glyburide, Glimepiride
- Other agents are generic (no cost advantage to Glyburide)
- Glyburide has been associated with worse cardiovascular outcomes in patients presenting for emergent PCI
- Glyburide appears to predispose to more severe Hypoglycemia than the other Second Generation Sulfonylureas
- Avoid in older adults
- Glyburide should be avoided in renal dysfunction where GFR <50-60 mL/min (increases hypglycemia risk)
- Glyburide should be avoided in severe hepatic dysfunction (increases Hypoglycemia risk)
- Gangji (2007) Diabetes Care 30:389-94 [PubMed]
- Glipizide may be preferred instead due to increased risks of Hypoglycemia associated with Glyburide, Glimepiride
-
Glyburide (DiaBeta, Micronase)
- Start: 2.5 to 5 mg orally daily with breakfast
- Usual: 5-20 mg orally daily
- Maximum: 20 mg orally daily
-
Glyburide Micronized (Glynase, PresTab)
- Start: 1.5 to 3 mg orally daily with breakfast
- Usual: 3-12 mg orally daily
- Maximum: 12 mg orally daily
IX. Adverse Effects
- See Sulfonylurea Poisoning
- Hemolytic Anemia in G6PD Deficiency Risk
- Weight gain
-
Hypoglycemia
- Higher risk of severe Hypoglycemia with Glyburide than other Sulfonylureas
- Hypoglycemia risk increases with lower GFR
- See Drug Interactions below for concurrent agents that increase Hypoglycemia risk
- Cardiovascular Disease does not appear to be at increased risk with Sulfonylureas
- Early studies had suggested possible increased Cardiovascular Risk
- Sulfonylureas appear to be neutral in their Cardiovascular Risk effects
- Contrast with GLP-1 Agonists and SGLT2 Inhibitors which reduce Cardiovascular Risk
- (2019) presc lett 26(12): 71
X. Safety
- Unknown safety in Lactation
- Unknown safety in pregnancy
- Discontinue at least 2 weeks before delivery
XI. Drug Interactions: Increased risk of Hypoglycemia with Sulfonylureas
XII. Efficacy
- Lower Hemoglobin A1C 0.8 to 1.5%
- Do not affect all-cause mortality
XIII. References
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Definition (CSP) | compounds of the type R-SO2-NHCONH-; when R=Ph, these are a group of hypoglycemic agents which enhance insulin secretion by beta cells and insulin sensitivity in target tissue, and so are effective in type II (noninsulin-dependent) diabetes mellitus. |
Concepts | Organic Chemical (T109) , Pharmacologic Substance (T121) |
MSH | D013453 |
SnomedCT | 273950002, 34012005, 372711004, 259552008 |
LNC | LP18787-9, MTHU005387 |
English | Compounds, Sulfonylurea, SULFONYLUREA CPDS, Sulfonylurea and its derivs, Sulphonylurea and its derivs, sulfonylureas (medication), sulfonylureas, sulfonylurea compounds, oral hypoglycemics sulfonylureas, Sulfonylurea Compounds, Sulfonylurea Compounds [Chemical/Ingredient], sulphonylureas, sulphonylurea, Sulfonylurea, Sulfonylurea compounds, Sulfonylurea product, Sulphonylurea, Sulphonylurea compounds, Sulphonylurea product, Sulfonylurea and its derivatives, Sulphonylurea and its derivatives, Sulfonylurea (product), Sulfonylurea (substance), Sulfonylurea and its derivatives (substance), sulfonylurea, Sulfonylurea, NOS, Sulfonylurea [dup] (substance), Sulfonylureas |
Swedish | Sulfonylureaföreningar |
Czech | sulfonylmočovinové sloučeniny, glibornurid, sulfonylureové deriváty, sulfonylureové sloučeniny |
Finnish | Sulfonyyliurea |
Russian | SUL'FONILMOCHEVINY SOEDINENIIA, GLIBORNURID, ГЛИБОРНУРИД, СУЛЬФОНИЛМОЧЕВИНЫ СОЕДИНЕНИЯ |
Croatian | SULFONILUREJA, SPOJEVI |
Polish | Sulfonylomocznika związki |
Portuguese | Compostos de Sulfonilureia |
Spanish | sulfonilurea (producto), sulfonilurea (sustancia), sulfonilurea y derivados (sustancia), sulfonilurea y derivados, sulfonilurea, Compuestos de Sulfonilurea |
French | Sulfonylurées |
German | Sulfonylharnstoffverbindungen |
Italian | Derivati della solfonilurea |
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 |