Glimepiride

Better effect in lean patients
Consider when Hemoglobin A1C <9%
Second-line to Metformin in most patients
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

Sulfa Allergy (applies to Sulfonylureas)
Renal and liver dysfunction
1. Use caution with Sulfonylureas (especially Glyburide)
2. Repaglinide or Nateglinide may be preferred here
3. Avoid most Sulfonylureas when GFR <60 ml/min (higher risk of Hypoglycemia)
  1. Glipizide Half-Life is not impacted by lower GFR and is safer to use in low GFR
Avoid Glyburide in cardiovascular disease (and in general due to Hypoglycemia risk)
1. Glimepiride and Glipizide do not appear to increase risk

Sulfonylureas trigger Insulin release from pancreatic beta cells
1. Sulfonylureas stimulate Potassium channel closure on pancreatic beta cell surface
2. Secretagogues do NOT burn out the beta cells sooner
Sulfonylureas may also increase tissue Insulin sensitivity

General
1. Increase dose every 1-2 weeks until adequate response
2. No response to Sulfonylureas in 25-30% of Type II Diabetics
Glimepiride (Amaryl)
1. Start: 1 to 2 mg orally daily taken orally with breakfast
  1. Start at 1 mg orally daily in elderly, renal or hepatic insufficiency, malnourished
2. Titrate in 1 to 2 mg increments at 1 to 2 week intervals
3. Usual: 4 mg orally daily
4. Maximum: 8 mg orally daily (doses above 4 mg daily, are unlikely to offer benefit)

See Sulfonylurea Poisoning
Hemolytic Anemia in G6PD Deficiency Risk
Weight gain
Hypoglycemia
1. Higher risk of severe Hypoglycemia with Glyburide than other Sulfonylureas
2. Hypoglycemia risk increases with lower GFR
3. See Sulfonylurea Drug Interactions Causing Hypoglycemia
Cardiovascular Disease
1. Early studies had suggested possible increased Cardiovascular Risk
2. Does not appear to be at increased risk with Sulfonylureas overall
  1. However, still avoid Glyburide in cardiovascular disease (and in general due to Hypoglycemia risk)
3. Glimepiride and Glipizide appear to be neutral in their Cardiovascular Risk effects
  1. Contrast with GLP-1 Agonists and SGLT2 Inhibitors which reduce Cardiovascular Risk
4. (2019) presc lett 26(12): 71

Unknown safety in Lactation
Unknown safety in pregnancy
1. Discontinue at least 2 weeks before delivery (risk of Neonatal Hypoglycemia)

See Sulfonylurea Drug Interactions Causing Hypoglycemia
Never combine Insulin Secretagogues (Sulfonylureas or Meglitinides)
1. They all have same site of activity
2. If one does not work, then all will not work

Sulfonylurea effects as a class
1. Lower Hemoglobin A1C 0.8 to 1.5%
2. Do not affect all-cause mortality
Glimepiride Specific Advantages
1. More rapid onset with longer duration
2. Lower Incidence of Hypoglycemia than Glyburide, but greater risk than Glipizide
3. Risk of Hypoglycemia increases with lower GFR
4. Preferred of class for Coronary Artery Disease