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Glipizide: Drug information

Glipizide: Drug information
2024© UpToDate, Inc. and its affiliates and/or licensors. All Rights Reserved.
For additional information see "Glipizide: Patient drug information"

For abbreviations, symbols, and age group definitions show table
Brand Names: US
  • glipiZIDE XL;
  • Glucotrol XL;
  • Glucotrol [DSC]
Brand Names: Canada
  • Glucotrol XL
Pharmacologic Category
  • Antidiabetic Agent, Sulfonylurea
Dosing: Adult
Diabetes mellitus, type 2, treatment

Diabetes mellitus, type 2, treatment:

Note: May be used as an adjunctive agent or alternative monotherapy for patients in whom initial therapy with lifestyle intervention and metformin failed or who cannot take metformin. Sulfonylureas are associated with a greater risk of hypoglycemia than other noninsulin antidiabetic agents; if one is chosen, a sulfonylurea with a lower relative risk of hypoglycemia (eg, glipizide, glimepiride) is preferred (Ref).

Immediate release:

Oral: Initial: 2.5 to 5 mg once daily 30 minutes before the first main meal; in patients whose glycemic levels are close to goal, use lower initial doses (eg, 2.5 mg once daily) to reduce the risk of hypoglycemia (Ref). In patients with severe hyperglycemia (eg, fasting glucose >250 mg/dL, HbA1c >9%) without ketonuria or spontaneous weight loss and in whom type 1 diabetes is unlikely, some experts use a higher initial dose of 10 mg twice daily 30 minutes before meals (Ref).

Dosage adjustment: May increase dose in 2.5 to 5 mg increments every 1 to 4 weeks if needed to achieve glycemic goals; usual maintenance dose: 2.5 to 10 mg/day (maximum effective dose: 20 mg/day) (Ref). Note: Increasing dosage to the labeled maximum dose of 40 mg/day has not been shown to improve glycemic control (Ref). Administer daily doses >15 mg/day in 2 divided doses given 30 minutes before meals; may also divide the daily dose into 2 doses if once-daily dosing does not provide adequate glycemic control.

Extended release:

Oral: Initial: 2.5 to 5 mg once daily with the first main meal; in patients whose glycemic levels are close to goal, use lower initial doses (eg, 2.5 mg once daily) to reduce the risk of hypoglycemia (Ref).

Dosage adjustment: May increase dose in 2.5 to 5 mg increments every 1 to 4 weeks if needed to achieve glycemic goals; usual maintenance dose: 5 to 10 mg/day (maximum: 20 mg/day) (Ref).

Glipizide conversion recommendations:

Conversion from IR to ER glipizide: May switch the IR total daily dose to the nearest equivalent daily dose of the ER tablet and administer once daily.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Altered kidney function:

Note: Glipizide is a preferred sulfonylurea in patients with chronic kidney disease (it has inactive metabolites) (Ref); however, conservative initial and maintenance dosing is recommended to avoid hypoglycemic events (Ref):

Oral: Immediate-release and extended-release tablets:

eGFR ≥50 mL/minute/1.73 m2: No dose adjustment necessary.

eGFR 10 to <50 mL/minute/1.73 m2: Initial: 2.5 mg once daily. May cautiously titrate based on glycemic control up to a maximum 20 mg/day (Ref).

eGFR <10 mL/minute/1.73 m2: Avoid use if possible (Ref). If necessary, initial dose of 2.5 mg once daily, may cautiously titrate based on glycemic control up to a maximum of 20 mg/day (Ref).

Hemodialysis, intermittent (thrice weekly): Not likely to be dialyzable (Ref).

Dose for eGFR <10 mL/minute, use with caution (Ref).

Peritoneal dialysis: Dose for eGFR <10 mL/minute, use with caution (Ref).

Dosing: Hepatic Impairment: Adult

Immediate release: Oral: Initial: 2.5 mg once daily; maintenance dosing should be conservative to avoid hypoglycemia

Extended release: Oral: Initial: 2.5 mg once daily; maintenance dosing should be conservative to avoid hypoglycemia

Dosing: Older Adult

Diabetes mellitus, type 2, treatment (alternative agent):

Note: Use of sulfonylureas (eg, glipizide) is associated with increased risk of hypoglycemia. The American Diabetes Association suggests using sulfonylureas with caution, and notes preference for glipizide (or glimepiride) due to lower relative risk of hypoglycemia compared to other sulfonylureas (Ref).

Immediate release: Oral: Initial: 2.5 mg once daily; consider titrating by 2.5 to 5 mg/day at 1- to 2-week intervals. Maintenance dosing should be conservative to avoid hypoglycemia.

Extended release: Oral: Initial: 2.5 mg once daily; maintenance dosing should be conservative to avoid hypoglycemia.

Adverse Reactions (Significant): Considerations
Cardiovascular effects

Product labeling states oral hypoglycemic drugs may be associated with an increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin. Data to support this association are limited, and several studies, including a large prospective trial (Ref), have not supported an association. In patients with established atherosclerotic cardiovascular disease, other agents are preferred (Ref).

Hypoglycemia

Use of sulfonylureas, including glipizide, may result in hypoglycemia, which may be severe. Shorter-acting sulfonylureas (eg, glipizide, gliclazide) are associated with a lesser risk of hypoglycemia as compared to their longer-acting counterparts and/or agents with active metabolites (eg, glimepiride, glyburide) (Ref); the duration of glipizide-induced hypoglycemia may be prolonged in patients receiving an extended-release formulation (Ref). In general, sulfonylureas are associated with a higher risk of hypoglycemia when compared to other non-insulin antihyperglycemic agents (eg, metformin, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 receptor agonists, thiazolidinediones) (Ref).

Mechanism: Dose-dependent (Ref); related to the pharmacologic action. Sulfonylureas stimulate the release of insulin from the pancreas.

Onset: Rapid; may occur after a single dose (Ref). Timing may be impacted by concomitant use of other antihyperglycemic medications, nutritional status (eg, caloric intake), dose titration, or accumulation.

Risk factors:

• Deficient caloric intake or malnourishment

• Rigorous or prolonged exercise

• Ingestion of alcohol

• Concomitant use of other antihyperglycemic agents (Ref)

• Concomitant use of antibiotics (Ref), fibrates (eg, gemfibrozil (Ref)), or warfarin (Ref)

• Older adults (eg, ≥65 years of age (Ref))

• Patients with poor general health

• Patients with impaired kidney function; Note: In patients with impaired kidney function, glipizide may be less likely to cause hypoglycemia as compared to other sulfonylureas as glipizide is metabolized by the liver and excreted in the urine as inactive metabolites. (Ref)

• Patients with impaired liver function

• Patients with pituitary insufficiency

• Patients with or at risk for hypoglycemia awareness; risk factors may include:

- Autonomic neuropathy

- Older adults

- Concomitant use of beta-blockers or other sympatholytic agents (Ref)

- Recent hypoglycemia (hypoglycemia-associated autonomic failure) (Ref)

- Patients that are heterozygous or homozygous for CYP2C9 variant alleles (*2 or *3) with subsequent decreased enzyme activity may be at an increased risk for sulfonylurea-induced hypoglycemia, especially with use of gliclazide (Ref).

Sulfonamide allergy

The FDA-approved product labeling for many medications containing a sulfonamide chemical group includes a broad contraindication in patients with a prior allergic reaction to any sulfonamide. Although there is a potential for cross-reactivity between antibiotic sulfonamides, concerns for cross-reactivity have previously extended to all compounds containing the sulfonamide structure (SO2NH2). An expanded understanding of allergic mechanisms indicates cross-reactivity between antibiotic sulfonamides and nonantibiotic sulfonamides is unlikely to occur (Ref).

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults and may include incidences from dosages exceeding the recommended dose.

1% to 10%:

Endocrine & metabolic: Hypoglycemia (3%)

Gastrointestinal: Abdominal pain (1%), constipation (<3%), diarrhea (1% to 5%), dyspepsia (<3%), flatulence (3%), nausea (<3%), vomiting (<3%)

Hypersensitivity: Hypersensitivity reaction (<2%; including eczema, erythema of skin, maculopapular rash, morbilliform rash, pruritus, urticaria)

Nervous system: Dizziness (2% to 7%), drowsiness (2%), headache (2%), nervousness (4%), tremor (4%)

Frequency not defined:

Endocrine & metabolic: Increased lactate dehydrogenase

Hepatic: Increased serum alkaline phosphatase, increased serum aspartate aminotransferase

Renal: Increased blood urea nitrogen, increased serum creatinine

Postmarketing:

Dermatologic: Skin rash

Endocrine & metabolic: Hyponatremia, SIADH

Hematologic & oncologic: Agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, pancytopenia, thrombocytopenia

Hepatic: Cholestatic jaundice, hepatic injury (can be induced with alcohol consumption) (Ilario 200), hepatic porphyria, jaundice

Neuromuscular & skeletal: Myopathy (Das 2016)

Miscellaneous: Disulfiram-like reaction

Contraindications

Hypersensitivity to glipizide, sulfonamide derivatives, or any component of the formulation; type 1 diabetes mellitus; diabetic ketoacidosis (with or without coma).

Note: Although the FDA-approved product labeling states this medication is contraindicated in patients with hypersensitivity to sulfonamide-containing drugs, the scientific basis of this cross-sensitivity has been challenged. See “Warnings/Precautions” for more detail.

Warnings/Precautions

Disease-related concerns:

• Bariatric surgery:

– Altered absorption: Use IR formulations after surgery to minimize the potential effects of bypassing stomach and proximal small bowel with gastric bypass or more rapid gastric emptying and proximal small bowel transit with sleeve gastrectomy (Apovian 2015). ER formulations may have altered release and absorption patterns after gastric bypass or sleeve gastrectomy (but not gastric band). Compared to control, Tmax in a gastric bypass cohort administered tolbutamide was significantly shorter (1.4 ± 1.8 vs 5.1 ± 1.7 hours; P < 0.001), while Cmax and AUC0- ∞ were not altered (Tandra 2013).

– Hypoglycemia: Use an antidiabetic agent without the potential for hypoglycemia if possible; hypoglycemia may occur after gastric bypass, sleeve gastrectomy, and gastric band (Mechanick 2020). Insulin secretion and sensitivity may be partially or completely restored after these procedures (gastric bypass is most effective, followed by sleeve and finally band) (Korner 2009; Peterli 2012). First-phase insulin secretion and hepatic insulin sensitivity have been shown to be significantly improved in the immediate days after gastric bypass and sleeve gastrectomy. The restorative effects of these procedures on peripheral insulin sensitivity may occur later in the 3- to 12-month period postsurgery (Mingrone 2016).

– Weight gain: Evaluate risk vs benefit and consider alternative therapy after gastric bypass, sleeve gastrectomy, and gastric banding; weight gain may occur (Apovian 2015).

• Glucose-6-phosphate dehydrogenase (G6PD) deficiency: Patients with G6PD deficiency may be at an increased risk of sulfonylurea-induced hemolytic anemia; however, cases have also been described in patients without G6PD deficiency during postmarketing surveillance. Use with caution and consider a nonsulfonylurea alternative in patients with G6PD deficiency.

• Hepatic impairment: Use with caution in patients with hepatic impairment.

• Renal impairment: Use with caution in patients with renal impairment.

• Stress-related states: It may be necessary to discontinue therapy and administer insulin if the patient is exposed to stress (fever, trauma, infection, surgery).

Dosage form specific issues:

• GI tract stricture/narrowing: The extended release formulation consists of drug within a nondeformable matrix; following drug release/absorption, the matrix/shell is expelled in the stool. The use of nondeformable products in patients with known stricture/narrowing of the GI tract has been associated with symptoms of obstruction. Avoid use of extended release tablets (Glucotrol XL) in patients with severe gastrointestinal narrowing or esophageal dysmotility.

Other warnings/precautions:

• Appropriate use: Not for use in patients with diabetic ketoacidosis (DKA) or patients with type 1 diabetes mellitus.

• Hospitalized patients: Consider temporary discontinuation of noninsulin antidiabetic agents and initiation or continuation of insulin therapy during hospitalization (ADA 2023). In noncritically ill hospitalized patients, continued use of glipizide may be considered if there are no contraindications, regular nutritional intake is expected, and blood glucose is well controlled; close monitoring and subsequent dosage adjustments are recommended (ADA/AACE [Moghissi 2009]; Bogun 2013; Inzucchi 2006).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral:

Glucotrol: 5 mg [DSC]

Glucotrol: 10 mg [DSC] [scored]

Generic: 2.5 mg, 5 mg, 10 mg

Tablet Extended Release 24 Hour, Oral:

glipiZIDE XL: 2.5 mg, 5 mg, 10 mg

Glucotrol XL: 2.5 mg [DSC], 5 mg, 10 mg

Generic: 2.5 mg, 5 mg, 10 mg

Generic Equivalent Available: US

Yes

Pricing: US

Tablet, 24-hour (glipiZIDE ER Oral)

2.5 mg (per each): $0.41

5 mg (per each): $0.41

10 mg (per each): $0.81

Tablet, 24-hour (Glucotrol XL Oral)

2.5 mg (per each): $0.47

5 mg (per each): $0.47

10 mg (per each): $0.85

Tablets (glipiZIDE Oral)

2.5 mg (per each): $1.84

5 mg (per each): $0.36 - $0.40

10 mg (per each): $0.59 - $0.65

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet Extended Release 24 Hour, Oral:

Glucotrol XL: 5 mg, 10 mg

Administration: Adult

Oral: Note: Patients that are NPO or require decreased caloric intake may need doses held to avoid hypoglycemia.

Immediate release: Administer 30 minutes before a meal (preferably before breakfast if once-daily dosing) to achieve greatest reduction in postprandial hyperglycemia.

Extended release: Administer with breakfast or the first meal of the day; swallow tablets whole, do not chew, divide or crush.

Bariatric surgery: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Switch to IR tablet. Avoid use of sulfonylureas immediately postoperative. Hormonal changes induced by surgery and low carbohydrate immediate postop diet could lead to profound hypoglycemia if sulfonylureas are administered.

Use: Labeled Indications

Diabetes mellitus, type 2, treatment: Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus

Medication Safety Issues
Sound-alike/look-alike issues:

GlipiZIDE may be confused with glimepiride, glyBURIDE

Glucotrol may be confused with Glucophage, Glucotrol XL, glyBURIDE, GlycoTrol (dietary supplement)

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (sulfonylurea hypoglycemics, oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).

Older Adult: High-Risk Medication:

Avoid routine use of sulfonylureas due to increased risk of hypoglycemia; however, if a sulfonylurea is needed, one with a lower relative risk of hypoglycemia (eg, gliclazide, glipizide, glimepiride) is preferred (ADA 2023; Beers Criteria [AGS 2023]; Diabetes Canada).

Metabolism/Transport Effects

Substrate of CYP2C9 (major), OATP1B1/1B3 (SLCO1B1/1B3); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Ajmaline: Sulfonamides may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. Risk C: Monitor therapy

Alcohol (Ethyl): Sulfonylureas may enhance the adverse/toxic effect of Alcohol (Ethyl). A flushing reaction may occur. Alcohol (Ethyl) may enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy

Alpha-Glucosidase Inhibitors: May enhance the hypoglycemic effect of Sulfonylureas. Management: Consider a decrease in sulfonylurea dose when initiating therapy with an alpha-glucosidase inhibitor and monitor patients for hypoglycemia. Risk D: Consider therapy modification

Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy

Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Risk X: Avoid combination

Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Risk C: Monitor therapy

Amiodarone: May enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy

Androgens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Antidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy

Beta-Blockers (Beta1 Selective): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy

Beta-Blockers (Nonselective): May enhance the hypoglycemic effect of Sulfonylureas. Beta-Blockers (Nonselective) may diminish the therapeutic effect of Sulfonylureas. Risk C: Monitor therapy

Bortezomib: May enhance the therapeutic effect of Antidiabetic Agents. Bortezomib may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Chloramphenicol (Systemic): May increase the serum concentration of Sulfonylureas. Risk C: Monitor therapy

Cimetidine: May increase the serum concentration of GlipiZIDE. Risk C: Monitor therapy

Clarithromycin: May enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy

Colesevelam: May decrease the serum concentration of Sulfonylureas. Management: Administer sulfonylureas 4 hours prior to colesevelam. Risk D: Consider therapy modification

CYP2C9 Inducers (Moderate): May decrease the serum concentration of Sulfonylureas. Risk C: Monitor therapy

CYP2C9 Inhibitors (Moderate): May increase the serum concentration of Sulfonylureas. Risk C: Monitor therapy

Dexketoprofen: May enhance the adverse/toxic effect of Sulfonamides. Risk C: Monitor therapy

Dipeptidyl Peptidase-IV Inhibitors: May enhance the hypoglycemic effect of Sulfonylureas. Management: Consider a decrease in sulfonylurea dose when initiating therapy with a dipeptidyl peptidase-IV inhibitor and monitor patients for hypoglycemia. Risk D: Consider therapy modification

Direct Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy

Elexacaftor, Tezacaftor, and Ivacaftor: May increase the serum concentration of GlipiZIDE. Risk C: Monitor therapy

Etilefrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Fibric Acid Derivatives: May enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy

Glucagon-Like Peptide-1 Agonists: May enhance the hypoglycemic effect of Sulfonylureas. Management: Consider sulfonylurea dose reductions when used in combination with glucagon-like peptide-1 agonists. Risk D: Consider therapy modification

Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy

Herbal Products with Glucose Lowering Effects: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy

Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Hypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Risk C: Monitor therapy

Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy

Indobufen: May increase the serum concentration of GlipiZIDE. Risk C: Monitor therapy

Lumacaftor and Ivacaftor: May decrease the serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may increase the serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Risk C: Monitor therapy

Maitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Mecamylamine: Sulfonamides may enhance the adverse/toxic effect of Mecamylamine. Risk X: Avoid combination

Methoxsalen (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Methoxsalen (Systemic). Risk C: Monitor therapy

Metreleptin: May enhance the hypoglycemic effect of Sulfonylureas. Management: Sulfonylurea dosage adjustments (including potentially large decreases) may be required to minimize the risk for hypoglycemia with concurrent use of metreleptin. Monitor closely for signs or symptoms of hypoglycemia. Risk D: Consider therapy modification

MetroNIDAZOLE (Systemic): May increase the serum concentration of Sulfonylureas. Risk C: Monitor therapy

Miconazole (Oral): May enhance the hypoglycemic effect of Sulfonylureas. Miconazole (Oral) may increase the serum concentration of Sulfonylureas. Risk C: Monitor therapy

Mitiglinide: May enhance the adverse/toxic effect of Sulfonylureas. Risk X: Avoid combination

Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Pegvisomant: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy

Posaconazole: May enhance the hypoglycemic effect of GlipiZIDE. Posaconazole may increase the serum concentration of GlipiZIDE. Risk C: Monitor therapy

Probenecid: May increase the serum concentration of Sulfonylureas. Risk C: Monitor therapy

Prothionamide: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Quinolones: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Quinolones may diminish the therapeutic effect of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Risk C: Monitor therapy

RaNITIdine (Withdrawn from US Market): May increase the serum concentration of GlipiZIDE. Risk C: Monitor therapy

Rifapentine: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Risk C: Monitor therapy

Ritodrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Salicylates: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors: May enhance the hypoglycemic effect of Sulfonylureas. Management: Consider a decrease in sulfonylurea dose when initiating therapy with a sodium-glucose cotransporter 2 (SGLT2) inhibitor and monitor patients for hypoglycemia. Risk D: Consider therapy modification

Sulfonamide Antibiotics: May enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy

Tetracyclines: May enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy

Tezacaftor and Ivacaftor: May increase the serum concentration of GlipiZIDE. Risk C: Monitor therapy

Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Thiazolidinediones: May enhance the hypoglycemic effect of Sulfonylureas. Management: Consider sulfonylurea dose adjustments in patients taking thiazolidinediones and monitor for hypoglycemia. Risk D: Consider therapy modification

Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Sulfonylureas may enhance the anticoagulant effect of Vitamin K Antagonists. Vitamin K Antagonists may enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy

Voriconazole: May increase the serum concentration of Sulfonylureas. Risk C: Monitor therapy

Food Interactions

Ethanol: May cause rare disulfiram reactions. Management: Monitor patients.

Food: A delayed release of insulin may occur if glipizide is taken with food. Management: Immediate release tablets should be administered 30 minutes before meals to avoid erratic absorption.

Reproductive Considerations

Sulfonylureas are not recommended for patients with type 2 diabetes mellitus planning to become pregnant. Patients who could become pregnant should use effective contraception during therapy. Transition to a preferred therapy should be initiated prior to conception and contraception should be continued until glycemic control is achieved (ADA 2023; Alexopoulos 2019; Egan 2020)

Pregnancy Considerations

Glipizide was found to cross the placenta in vitro (Elliott 1994).

Severe hypoglycemia lasting 4 to 10 days has been noted in infants born to mothers taking a sulfonylurea at the time of delivery. The manufacturer recommends if glipizide is used during pregnancy, it should be discontinued at least 2 weeks before the expected delivery date.

Poorly controlled diabetes during pregnancy can be associated with an increased risk of adverse maternal and fetal outcomes, including diabetic ketoacidosis, preeclampsia, spontaneous abortion, preterm delivery, delivery complications, major malformations, stillbirth, and macrosomia. To prevent adverse outcomes, prior to conception and throughout pregnancy, maternal blood glucose and HbA1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ADA 2023; Blumer 2013).

Agents other than glipizide are currently recommended to treat diabetes mellitus in pregnancy (ADA 2023).

Breastfeeding Considerations

Data from two mother-infant pairs note that glipizide was not detected in breast milk (Feig 2005).

Current guidelines note that breastfeeding is encouraged for all women, including those with diabetes (ACOG 201 2018; ADA 2023; Blumer 2013). A small snack before breastfeeding may help decrease the risk of hypoglycemia in women with pregestational diabetes (ACOG 201 2018; Reader 2004).

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. Monitor the infant for hypoglycemia.

Dietary Considerations

Take immediate release tablets 30 minutes before meals (preferably before breakfast if once-daily dosing); extended release tablets should be taken with breakfast or the first meal of the day. Individualized medical nutrition therapy (MNT) based on ADA recommendations is an integral part of therapy.

Monitoring Parameters

Signs and symptoms of hypoglycemia (fatigue, excessive hunger, profuse sweating, numbness of extremities), blood glucose; renal function; liver function; weight (due to potential to cause weight gain).

HbA1c: Monitor at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; monitor quarterly in patients in whom treatment goals have not been met, or with therapy change. Note: In patients prone to glycemic variability (eg, patients with insulin deficiency), or in patients whose HbA1c is discordant with serum glucose levels or symptoms, consider evaluating HbA1c in combination with blood glucose levels and/or a glucose management indicator (ADA 2023; KDIGO 2020).

Reference Range

Recommendations for glycemic control in patients with diabetes:

Nonpregnant adults with diabetes (AACE [Samson 2023], ADA 2023):

HbA1c: <7% (a more aggressive [<6.5%] or less aggressive [<8%] HbA1c goal may be targeted based on patient-specific characteristics). Note: In patients using a continuous glucose monitoring system, a goal of time in range >70% with time below range <4% is recommended and is similar to a goal HbA1c <7%.

Preprandial capillary blood glucose: 80 to 130 mg/dL (SI: 4.4 to 7.2 mmol/L) (more or less stringent goals may be appropriate based on patient-specific characteristics).

Peak postprandial capillary blood glucose (~1 to 2 hours after a meal): <180 mg/dL (SI: <10 mmol/L) (more or less stringent goals may be appropriate based on patient-specific characteristics).

Older adults (≥65 years of age) (ADA 2023):

Note: Consider less strict targets in patients who are using insulin and/or insulin secretagogues (sulfonylureas, meglitinides) (ES [LeRoith 2019]).

HbA1c: <7% to 7.5% (healthy); <8% (complex/intermediate health). Note: Individualization may be appropriate based on patient and caregiver preferences and/or presence of cognitive impairment. In patients with very complex or poor health (ie, limited remaining life expectancy), consider making therapy decisions based on avoidance of hypoglycemia and symptomatic hyperglycemia rather than HbA1c level.

Preprandial capillary blood glucose: 80 to 130 mg/dL (SI: 4.4 to 7.2 mmol/L) (healthy); 90 to 150 mg/dL (SI: 5 to 8.3 mmol/L) (complex/intermediate health); 100 to 180 mg/dL (SI: 5.6 to 10 mmol/L) (very complex/poor health).

Bedtime capillary blood glucose: 80 to 180 mg/dL (SI: 4.4 to 10 mmol/L) (healthy); 100 to 180 mg/dL (SI: 5.6 to 10 mmol/L) (complex/intermediate health); 110 to 200 mg/dL (SI: 6.1 to 11.1 mmol/L) (very complex/poor health).

Classification of hypoglycemia (ADA 2023):

Level 1: 54 to 70 mg/dL (SI: 3 to 3.9 mmol/L); hypoglycemia alert value; initiate fast-acting carbohydrate (eg, glucose) treatment.

Level 2: <54 mg/dL (SI: <3 mmol/L); threshold for neuroglycopenic symptoms; requires immediate action.

Level 3: Hypoglycemia associated with a severe event characterized by altered mental and/or physical status requiring assistance.

Mechanism of Action

Stimulates insulin release from the pancreatic beta cells; reduces glucose output from the liver; insulin sensitivity is increased at peripheral target sites

Pharmacokinetics (Adult Data Unless Noted)

Duration: 12 to 24 hours

Absorption: Immediate release: Rapid and complete; delayed with food

Distribution: 10 to 11 L

Protein binding: 98% to 99%; primarily to albumin

Bioavailability: 90% to 100%

Metabolism: Hepatic via CYP2C9; forms metabolites (inactive)

Half-life elimination: 2 to 5 hours

Time to peak: 1 to 3 hours; extended release tablets: 6 to 12 hours

Excretion: Urine (<10% as unchanged drug; 80% as metabolites); feces (10%)

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Glipom | Minidiab | Sucrazide;
  • (AR) Argentina: Glipizida gen med | Minodiab;
  • (AT) Austria: Glibenese | Minidiab;
  • (AU) Australia: Melizide | Minidiab;
  • (BD) Bangladesh: Actine | Diactin | Diaplus | Glimerol | Zitrol;
  • (BE) Belgium: Glibenese | Minidiab;
  • (BG) Bulgaria: Antidiab | Glucopress | Minidiab;
  • (BR) Brazil: Glipgen | Glipizida | Minidiab;
  • (CH) Switzerland: Glibenese;
  • (CL) Chile: Minidiab | Xiprine;
  • (CN) China: Di sha | Ge li shu | Ge lie shu | Glipizde | Glutrol | Kang er bi da | Le tou fu | Man di bao | Mei bi da | Minidiab | Mitoneu | Qin su | Sheng qin | Si le ke | Tang ge lie | Tang ke tai | You da ling;
  • (CZ) Czech Republic: Antidiab | Minidiab;
  • (DO) Dominican Republic: Glifel | Minodiab;
  • (EE) Estonia: Antidiab | Glibenese | Glibenese gits | Minidiab;
  • (EG) Egypt: Glibenase | Glupizide | Minidiab;
  • (ES) Spain: Minodiab;
  • (FI) Finland: Apamid | Glibenese | Glipizid generics | Melizid | Mindiab;
  • (FR) France: Glibenese | Glipizide merck | Minidiab;
  • (GB) United Kingdom: Glibenese | Glipizide cox | Glipizide kent | Glipizide Myplan | Glipizide sandoz | Minodiab;
  • (GR) Greece: Glibenese | Minodiab;
  • (HK) Hong Kong: Diasef | Minidiab | Sunglucon;
  • (HU) Hungary: Minidiab;
  • (ID) Indonesia: Aldiab | Glyzid | Minidiab;
  • (IE) Ireland: Glibenese;
  • (IN) India: Bimode | D-glip | Diacon | Diaglip | Dibizide | G-trol | Glez | Glibetic | Glide | Glip | Glipicontin | Glipikem | Glipixor | Glipy | Glucolip | Glucotrol | Glynase | Glyson | Glytop | Glyzip | Lipi | Semi glynase;
  • (IT) Italy: Minidiab;
  • (JO) Jordan: Glibenese | Glipiram | Minidiab | Sucrazide;
  • (KE) Kenya: Diactin | Glipistin;
  • (KR) Korea, Republic of: Digrin | Durimon;
  • (KW) Kuwait: Minidiab;
  • (LB) Lebanon: Minidiab;
  • (LT) Lithuania: Antidiab | Glibenese | Minidiab;
  • (LU) Luxembourg: Glibenese | Minidiab;
  • (LV) Latvia: Glibenese | Minidiab;
  • (MA) Morocco: Minidiab;
  • (MX) Mexico: Flumedil | Gabaz | Glipizida | Glupitel | Luditec | Minodiab | Pigloss | Singloben;
  • (MY) Malaysia: Dibizide | Glix | Melizide | Minidiab;
  • (NG) Nigeria: Greelip;
  • (NL) Netherlands: Glibenese;
  • (NO) Norway: Apamid | Glipizid | Mindiab;
  • (NZ) New Zealand: Minidiab;
  • (OM) Oman: Glipom;
  • (PE) Peru: Minidiab;
  • (PH) Philippines: Glipdin | Glucozide | Gluzid | Minidiab;
  • (PK) Pakistan: Glibenese | Glipase | Minidiab;
  • (PL) Poland: Antidiab | Glibenese | Glipizide bp | Minidiab;
  • (PR) Puerto Rico: Glucotrol;
  • (PT) Portugal: Minidiab;
  • (QA) Qatar: Glipom | Minidiab | Minodiab | Sucrazide;
  • (RU) Russian Federation: Antidiab | Glibenese | Glynase | Minidiab | Movogleken;
  • (SA) Saudi Arabia: Minidiab | Sucrazide;
  • (SE) Sweden: Glipiscand | Glipizid meda | Mindiab;
  • (SG) Singapore: Beapizide | Diasef | Glipizide Shin Poong | Melizide | Minidiab | Sunglucon;
  • (SI) Slovenia: Antidiab;
  • (SK) Slovakia: Antidiab | Minidiab;
  • (TH) Thailand: Apamid | Depizide | Diasef | Dipazide | Gipzide | Glibezide | Glimax | Glipidiab | Glipizide nida | Glizide | Glucodiab | Glycediab | Glygen | Gp zide | Melizide | Minibit | Minidiab | Namedia | Topizide | Tozide;
  • (TN) Tunisia: Sucrazide;
  • (TR) Turkey: Minidiab;
  • (TW) Taiwan: Contan | Diabes | Glibetin | Glicon | Glidiab | Glipin | Glix | Glucozide | Glupizide | Glutrol | Loil | Minidiab;
  • (UA) Ukraine: Glynase | Minidiab;
  • (UG) Uganda: Glynase;
  • (VE) Venezuela, Bolivarian Republic of: Minidiab;
  • (VN) Viet Nam: Gliptis;
  • (ZA) South Africa: Minidiab;
  • (ZM) Zambia: Glynase xl
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