Glipizide

Aka: Glipizide, Glucotrol, Glucotrol XL

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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. Glipizide Half-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: Glipizide

  1. Glipizide (Glucotrol) tablets 5 mg, 10 mg
  2. Glipizide Extended Release (Glucotrol XL) tablets 2.5 mg, 5 mg, 10 mg
    1. Advantages: Least expensive Sulfonylurea, long acting Sulfonylureas are preferred
    2. Disadvantages: Extended release may increase Hypoglycemia risk when compared with immediate release

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
    3. Long acting Sulfonylureas are preferred, but Glipizide XL may be at higher risk of Hypoglycemia
  2. Glipizide (Glucotrol)
    1. Start: 5 mg orally daily
      1. Start at 2.5 mg orally daily in elderly or liver disease
    2. Titrate in 2.5 to 5 mg increments
    3. Usual: 10-20 mg orally daily
    4. Daily doses >15 mg should be divided twice daily
    5. Maximum: 20 mg orally twice daily (40 mg/day)
  3. Glipizide Extended Release (Glucotrol XL)
    1. Start: 5 mg orally daily taken 30 minutes before breakfast
    2. Usual: 5 to 10 mg orally daily
    3. Maximum: 20 mg orally daily
      1. Doses above 10 mg daily ER, are unlikely to offer benefit (divide twice daily if used)

VII. Adverse Effects

  1. See Sulfonylurea Poisoning
  2. Hemolytic Anemia in G6PD Deficiency Risk
  3. Weight gain
  4. Hypoglycemia
    1. See Sulfonylurea Drug Interactions Causing Hypoglycemia
    2. Higher risk of severe Hypoglycemia with Glyburide than other Sulfonylureas
    3. Hypoglycemia risk increases with lower GFR
    4. Glipizide may be preferred instead due to increased risks of Hypoglycemia associated with Glyburide, Glimepiride
      1. Other agents are generic (no cost advantage to Glyburide)
  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

XI. Resources

  1. Glipizide (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=3e21bcc7-6f0d-4d63-befd-aa3ac8c63e37
  2. Glipizide ER (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f4b2b88c-946c-4670-8538-84f858b7af33

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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Related Studies

Cost: Medications

glipizide (on 10/19/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
GLIPIZIDE 10 MG TABLET Generic $0.05 each
GLIPIZIDE 5 MG TABLET Generic $0.03 each
GLIPIZIDE ER 10 MG TABLET Generic $0.17 each
GLIPIZIDE ER 2.5 MG TABLET Generic $0.14 each
GLIPIZIDE ER 5 MG TABLET Generic $0.11 each
GLIPIZIDE XL 10 MG TABLET Generic $0.17 each
GLIPIZIDE XL 2.5 MG TABLET Generic $0.14 each
GLIPIZIDE XL 5 MG TABLET Generic $0.11 each
GLIPIZIDE-METFORMIN 2.5-250 MG Generic $0.29 each
GLIPIZIDE-METFORMIN 2.5-500 MG Generic $0.26 each
GLIPIZIDE-METFORMIN 5-500 MG Generic $0.27 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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