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
-
Sulfonylureas trigger Insulin release from pancreatic beta cells
- Sulfonylureas stimulate Potassium channel closure on pancreatic beta cell surface
- Secretagogues do NOT burn out the beta cells sooner
- Sulfonylureas may also increase tissue Insulin sensitivity
V. Medications: Glimepiride
- Glimepiride (Amaryl) 1 mg, 2 mg, 4 mg
VI. Dosing
-
General
- Increase dose every 1-2 weeks until adequate response
- No response to Sulfonylureas in 25-30% of Type II Diabetics
- Glimepiride (Amaryl)
- Start: 1 to 2 mg orally daily taken orally with breakfast
- Start at 1 mg orally daily in elderly, renal or hepatic insufficiency, malnourished
- Titrate in 1 to 2 mg increments at 1 to 2 week intervals
- Usual: 4 mg orally daily
- Maximum: 8 mg orally daily (doses above 4 mg daily, are unlikely to offer benefit)
- Start: 1 to 2 mg orally daily taken orally with breakfast
VII. 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 Sulfonylurea Drug Interactions Causing Hypoglycemia
- Cardiovascular Disease
- Early studies had suggested possible increased Cardiovascular Risk
- Does not appear to be at increased risk with Sulfonylureas overall
- However, still avoid Glyburide in cardiovascular disease (and in general due to Hypoglycemia risk)
- Glimepiride and Glipizide 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
VIII. Safety
- Unknown safety in Lactation
- Unknown safety in pregnancy
- Discontinue at least 2 weeks before delivery (risk of Neonatal Hypoglycemia)
IX. Drug Interactions
- See Sulfonylurea Drug Interactions Causing Hypoglycemia
- Never combine Insulin Secretagogues (Sulfonylureas or Meglitinides)
- They all have same site of activity
- If one does not work, then all will not work
X. Efficacy
-
Sulfonylurea effects as a class
- Lower Hemoglobin A1C 0.8 to 1.5%
- Do not affect all-cause mortality
- Glimepiride Specific 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
XI. Resources
Images: Related links to external sites (from Bing)
Related Studies
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 |
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 |