Glimepiride

Aka: Glimepiride, Amaryl

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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. Contraindications

  1. Sulfa Allergy (applies to Sulfonylureas)
  2. 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. GlipizideHalf-Life is not impacted by lower GFR and is safer to use in low GFR
  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. 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
  2. Sulfonylureas may also increase tissue Insulin sensitivity

V. Medications: Glimepiride

  1. Glimepiride (Amaryl) 1 mg, 2 mg, 4 mg

VI. Dosing

  1. General
    1. Increase dose every 1-2 weeks until adequate response
    2. No response to Sulfonylureas in 25-30% of Type II Diabetics
  2. 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)

VII. Adverse Effects

  1. See Sulfonylurea Poisoning
  2. Hemolytic Anemia in G6PD Deficiency Risk
  3. Weight gain
  4. 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
  5. 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

VIII. Safety

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

IX. Drug Interactions

  1. See Sulfonylurea Drug Interactions Causing Hypoglycemia
  2. 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

X. Efficacy

  1. Sulfonylurea effects as a class
    1. Lower Hemoglobin A1C 0.8 to 1.5%
    2. Do not affect all-cause mortality
  2. 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

XI. Resources

  1. Glimepiride (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=07ad4366-4b21-f633-49f3-c2b35f88168d

XII. 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]
  5. Vaughan (2024) Am Fam Physician 109(4): 333-42 [PubMed]

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Cost: Medications

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
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. GoodRx is another tool for finding lower drug prices.

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