Drug class: Sulfonylureas

Medically reviewed by Drugs.com on Jun 10, 2025. Written by ASHP.

Introduction

Antidiabetic agent; sulfonylurea.

Uses for Glipizide

Type 2 Diabetes Mellitus

Used as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Used as monotherapy and in combination with other antidiabetic agents (e.g., metformin, thiazolidinedione).

Commercially available as a single entity preparation and in fixed combination with metformin.

Guidelines from the American Diabetes Association (ADA) and other experts generally recommend that use of sulfonylureas for the treatment of type 2 diabetes mellitus be limited or discontinued due to increased risk of weight gain and hypoglycemia. Sulfonylureas may be considered in patients with access or cost barriers to other antidiabetic regimens. When used, these guidelines recommend the lowest possible dosage. When selecting a treatment regimen for type 2 diabetes mellitus, consider factors such as cardiovascular and renal comorbidities, drug efficacy and adverse effects, hypoglycemia risk, presence of overweight or obesity, cost, access, and patient preferences. Weight management should be included as a distinct treatment goal and other healthy lifestyle behaviors should also be considered.

Not indicated for treatment of type 1 diabetes mellitus or diabetic ketoacidosis.

Glipizide Dosage and Administration

General

Patient Monitoring

• Monitor patients carefully to determine the need for continued therapy and to ensure the drug continues to be effective. In patients usually well controlled by dietary management alone, short-term therapy with glipizide may be sufficient during periods of transient loss of glycemic control.

• Monitor therapy with regular clinical and laboratory evaluations, including blood and urine glucose determinations, to determine the minimum effective dosage and to detect primary failure (inadequate lowering of blood glucose concentration at maximum recommended dosage) or secondary failure (loss of control of blood glucose following an initial period of effectiveness). HbA_1c measurements may also be useful for monitoring patient response.

Dispensing and Administration Precautions

• Based on the Institute for Safe Medication Practices (ISMP), glipiZIDE is a high-alert medication that has a heightened risk of causing significant patient harm when used in error.

• The ISMP includes glipiZIDE and glyBURIDE on the ISMP List of Confused Drug Names, and recommends special safeguards to ensure the accuracy of prescriptions for these drugs.

• The 2023 American Geriatrics Society (AGS) Beers Criteria for Potentially Inappropriate Medication (PIM) Use in Older Adults includes all sulfonylureas on the list of PIMs that are best avoided by older adults in most circumstances or under specific situations, such as certain diseases, conditions, or care settings. The criteria are intended to apply to adults ≥65 years of age in all ambulatory, acute, and institutional settings of care, except hospice and end-of-life care settings. The Beers Criteria Expert Panel specifically recommends to avoid sulfonylureas as first- or second-line monotherapy or add-on therapy unless there are substantial barriers to the use of safer and more effective agents; if a sulfonylurea is used, choose short-acting agents (e.g., glipizide) over long-acting agents (e.g., glyburide, glimepiride).

Administration

Oral Administration

Commercially available as single-entity tablets or in fixed combination with metformin hydrochloride.

Immediate-release tablets: Usually administered initially as a single daily dose in the morning before breakfast; recommended to administer 30 minutes before meal to achieve maximum reduction in postprandial blood glucose concentration. Once-daily dosing at dosages up to 15—20 mg shown to provide adequate control of blood glucose throughout the day in most patients with usual meal patterns; however, some may have a more satisfactory response when administered as 2 or 3 divided doses. Dosages exceeding 15—20 mg daily should be administered in divided doses before meals of sufficient caloric content. When divided-dosing regimen employed in patients receiving more than 15 mg daily, doses and schedule of administration should be individualized according to patient's meal pattern and response. Dosages greater than 30 mg daily have been given safely in twice-daily dosing regimens for prolonged periods. When given concomitantly with colesevelam, administer glipizide at least 4 hours prior to colesevelam.

Extended-release tablets: Administer once daily, generally with breakfast or first main meal of the day. Swallow whole and do not divide, chew, or crush. Patients receiving extended-release tablets may occasionally notice a tablet-like substance in their stools; this is normal since tablet containing drug is designed to remain intact and slowly release drug from a nonabsorbable shell during passage through GI tract. When given concomitantly with colesevelam, administer glipizide at least 4 hours prior to colesevelam.

Fixed combination of glipizide and metformin hydrochloride: Should be taken once or twice daily with food. See full prescribing information for additional instructions for combination product.

Dosage

Adults

Type 2 Diabetes Mellitus

Glipizide

Oral

Initially, 5 mg once daily.

In patients predisposed to hypoglycemia (e.g., debilitated, malnourished, or geriatric patients; those with hepatic or renal impairment; patients taking other antidiabetic drugs), initial dosage of 2.5 mg daily recommended.

Subsequent dosage should be adjusted according to patient's tolerance and therapeutic response.

Immediate-release tablets: Adjust dosage in increments of 2.5—5 mg at intervals of at least several days. Dosages above 15 mg daily should be divided; total daily dosages above 30 mg have safely been given twice daily.

Extended-release tablets: Patients receiving immediate-release tablets may be switched to extended-release tablets by giving nearest equivalent total daily dosage once daily.

Transition period generally not required when transferring from other oral antidiabetic agents to immediate-release tablets. Patients being transferred from longer half-life sulfonylureas should be monitored for hypoglycemia during initial 1—2 weeks of transition period due to potential for overlapping drug effect.

Maintenance dosage of glipizide varies considerably, ranging from 2.5—40 mg daily. Most patients require 5—25 mg daily as immediate-release tablets or 5—10 mg daily as extended release tablets, but some clinicians report higher dosages may be necessary. Maximum daily dosage is 40 mg daily as immediate-release tablets or 20 mg daily as extended-release tablets.

Transitioning from Insulin Therapy

Patients maintained on insulin dosages ≤20 units daily: May transfer directly to usual recommended initial dosage of glipizide and administration of insulin may be abruptly discontinued.

Patients requiring insulin dosages >20 units daily: Usual initial recommended dosage of glipizide should be started and insulin dosage reduced by 50%. Subsequently, insulin is withdrawn gradually and dosage of glipizide is adjusted at intervals of at least several days according to patient's tolerance and therapeutic response.

During period of insulin withdrawal, patients should test urine at least 3 times daily for glucose and ketones, and should be instructed to report results to clinician so that appropriate adjustments can be made, if necessary. In some patients, especially those requiring greater than 40 units of insulin daily, manufacturer suggests it may be advisable to consider hospitalization during the transition from insulin to glipizide.

Glipizide/Metformin Hydrochloride Fixed-combination Therapy

Oral

Initially, 2.5 mg of glipizide and 250 mg metformin hydrochloride once daily. In patients with more severe hyperglycemia (i.e., fasting plasma glucose 280—320 mg/dL), initial dosage of 2.5 mg of glipizide and 500 mg of metformin hydrochloride twice daily may be considered. Efficacy not established in patients with fasting plasma glucose concentrations exceeding 320 mg/dL.

Increase dosage in increments of 1 tablet daily every 2 weeks until minimum effective dosage required to achieve adequate glycemic control or to a maximum daily dosage of 10 mg of glipizide and 2 g of metformin hydrochloride reached.

Patients inadequately controlled with sulfonylurea or metformin monotherapy: Initially, 2.5 or 5 mg of glipizide and 500 mg of metformin hydrochloride twice daily with morning and evening meals. Initial dosage in fixed combination should not exceed daily dosage of glipizide or metformin hydrochloride already being taken to minimize risk of hypoglycemia. Dosage of fixed combination should be titrated upwards in increments not exceeding 5 mg of glipizide and 500 mg of metformin hydrochloride until adequate glycemic control or maximum daily dosage of 20 mg of glipizide and 2 g of metformin hydrochloride is reached.

Patients currently receiving glipizide (or other sulfonylurea agent) and metformin (administered as separate tablets): Initially, 2.5 or 5 mg of glipizide and metformin 500 mg tablets; initial dosage of fixed-combination preparation should not exceed daily dosages of glipizide (or equivalent dosage of other sulfonylurea) and metformin hydrochloride currently being taken. When transferring from previous therapy to fixed combination preparation, decision to switch to nearest equivalent dosage or titrate dosage is based on clinical judgment. Hypoglycemia and hyperglycemia is possible in such patients and change in therapy should be undertaken with appropriate monitoring. Safety and efficacy of switching from combined therapy with separate preparations to the fixed-combination preparation have not been established in clinical studies.

Special Populations

Hepatic Impairment

Glipizide Monotherapy

Immediate release: Initial dosage of 2.5 mg recommended; initial and maintenance dosage should be conservative to avoid hypoglycemic reactions.

Extended release: Initial dosage of 2.5 mg recommended.

Glipizide/Metformin Hydrochloride Fixed-combination Therapy

Avoid use in patients with clinical or laboratory evidence of hepatic disease.

Renal Impairment

Glipizide Monotherapy

Immediate release: No specific population dosage recommendations at this time; initial and maintenance dosage should be conservative to avoid hypoglycemic reactions.

Extended release: No specific population dosage recommendations at this time.

Glipizide/Metformin Hydrochloride Fixed-combination Therapy

Do not initiate in patients with eGFR between 30—45 mL/minute per 1.73 m².

Contraindicated if eGFR is <30 mL/minute per 1.73 m².

If patient already taking and eGFR falls below 45 mL/minute per 1.73 m², assess benefits and risks of continuing therapy. Discontinue if eGFR falls below 30 mL/minute per 1.73 m².

Geriatric Patients

Glipizide Monotherapy

Immediate release: Initial starting dosage of 2.5 mg recommended; dosage selection should be conservative, usually starting at low end of dosage range, reflecting greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy, to avoid hypoglycemic reactions.

Extended release: Initial dosage of 2.5 mg recommended.

Glipizide/Metformin Hydrochloride Fixed-combination Therapy

No specific population dosage recommendations at this time; do not titrate to maximum dosage to avoid risk of hypoglycemia. Initial and maintenance dosage selection should be conservative, usually starting at low end of dosage range, reflecting greater frequency of decreased renal function.

Cautions for Glipizide

Contraindications

• Known hypersensitivity to the drug or any ingredients in the formulation.

• Known hypersensitivity to sulfonamide derivatives.

• Diabetic ketoacidosis with or without coma. Diabetic ketoacidosis should be treated with insulin.

• Type 1 diabetes mellitus.

Warnings/Precautions

Increased Risk of Cardiovascular Mortality

Administration of oral hypoglycemic drugs reported to be associated with increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin.

Warning based on study conducted by the University Group Diabetes Program (UGDP), which reported that administration of oral antidiabetic agents was associated with increased cardiovascular mortality compared to diet alone or diet and insulin. Results of the UGDP study exhaustively analyzed and there has been general disagreement in scientific and medical communities regarding study's validity and clinical importance. Results from the United Kingdom Prospective Diabetes (UKPD) study, a large, long-term (over 10 years) study in newly diagnosed type 2 diabetes did not confirm increase in cardiovascular events or mortality in group treated intensively with sulfonylureas, insulin, or combination therapy compared with less intensive conventional antidiabetic therapy.

Although only one drug in the sulfonylurea class (tolbutamide) was included in the UGDP study, it is prudent from a safety standpoint to consider that this warning may also apply to other hypoglycemic drugs in this class, in view of their similarities in mode of action and chemical structure. Patients should be informed of potential risks and advantages of glipizide and of alternative therapies.

Macrovascular Outcomes

Manufacturer states there are no clinical studies that conclusively establish macrovascular risk reduction with glipizide or any other antidiabetic drug.

Renal and Hepatic Disease

Metabolism and excretion of glipizide may be slowed in patients with renal and/or hepatic impairment. If hypoglycemia occurs in such patients, it may be prolonged and appropriate management should be instituted.

Hypoglycemia

All sulfonylurea drugs are capable of causing severe hypoglycemia. Hypoglycemia may occur in patients receiving glipizide alone or when used in combination with other antidiabetic agents; concomitant use with other antidiabetic agents increases risk of hypoglycemia.

Ability to concentrate and react may be impaired as a result of hypoglycemia. Severe hypoglycemia can lead to unconsciousness or convulsions and may result in temporary or permanent impairment of brain function or death.

Early warning signs of hypoglycemia may be different or less pronounced in patients with autonomic neuropathy, in geriatric patients, and in patients taking β-adrenergic blocking agents. These situations may result in severe hypoglycemia before the patient is aware of the hypoglycemia.

Appropriate patient selection and careful attention to dosage are important to avoid glipizide-induced hypoglycemia. If hypoglycemia occurs during therapy with the drug, immediate reevaluation and adjustment of glipizide dosage and/or patient's meal pattern are necessary. A lower dosage of glipizide may be required to minimize risk of hypoglycemia when used concomitantly with other antidiabetic agents. Educate patients to recognize and manage hypoglycemia.

Loss of Glycemic Control

When a patient stabilized on any antidiabetic regimen is exposed to stress (e.g., fever, trauma, infection, or surgery), loss of glycemic control may occur. At times, it may be necessary to discontinue glipizide and administer insulin.

Effectiveness of any oral hypoglycemic drug in lowering blood glucose to a desirable level decreases in many patients over a period of time, which may be due to progression of severity of disease or diminished responsiveness to the drug.

Hemolytic Anemia

Patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency who receive sulfonylureas may develop hemolytic anemia. In patients with G6PD deficiency, a non-sulfonylurea antidiabetic agent should be considered.

Hemolytic anemia also reported with glipizide during postmarketing experience in patients who did not have known G6PD deficiency.

Gastrointestinal Obstruction

Obstructive symptoms in patients with known strictures reported in association with another drug with a non-dissolvable extended release formulation.

Avoid use of extended-release glipizide tablets (Glucotrol XL) in patients with preexisting gastrointestinal narrowing (pathologic or iatrogenic).

Use of Fixed Combinations

When glipizide is used in fixed combination with metformin, the cautions, precautions, and contraindications associated with metformin must be considered in addition to those associated with glipizide.

Specific Populations

Pregnancy

Available data from a small number of published studies and postmarketing experience with extended-release glipizide tablets in pregnancy over decades have not identified any drug-associated risks for major birth defects, miscarriage, or adverse maternal outcomes.

Poorly controlled diabetes mellitus in pregnancy carries risk to the mother and fetus; however, use of glipizide is generally not recommended and should be used only when clearly necessary (i.e., when insulin therapy is infeasible).

Neonates born to women with gestational diabetes treated with sulfonylureas during pregnancy may be at increased risk for neonatal intensive care admission and may develop respiratory distress, hypoglycemia, or birth injury; they also may be large for gestational age. Prolonged, severe hypoglycemia lasting up to 4—10 days has been reported in some neonates born to women receiving sulfonylureas up to the time of delivery; this effect has been reported more frequently with use of agents having prolonged elimination half-lives. To minimize risk of neonatal hypoglycemia if glipizide is used during pregnancy, discontinue drug at least 2 weeks before expected delivery date. Neonates should be observed for symptoms of hypoglycemia and respiratory distress and managed accordingly.

Lactation

Unknown whether glipizide is distributed into milk in humans; some sulfonylureas are distributed into human milk. No data on effects on milk production. Developmental and health benefits of breast-feeding should be considered along with mother's clinical need for glipizide and any potential adverse effects on the breast-fed child from glipizide or underlying maternal condition. If used during breast-feeding, infants should be monitored for signs of hypoglycemia (e.g., jitters, cyanosis, apnea, hypothermia, excessive sleepiness, poor feeding, seizures). If glipizide is discontinued and dietary management alone is inadequate for controlling blood glucose concentration, administration of insulin should be considered.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

No overall differences in effectiveness or safety between younger and older patients, but greater sensitivity cannot be ruled out. Geriatric patients are particularly susceptible to hypoglycemic action of antidiabetic agents; hypoglycemia may be difficult to recognize in these patients. In general, dosage selection should be cautious, usually starting at the low end of dosage range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Hepatic Impairment

No information regarding effects of hepatic impairment on glipizide disposition. As glipizide is highly protein bound and hepatic biotransformation is predominant route of elimination, pharmacokinetics and/or pharmacodynamics may be altered in hepatic impairment. If hypoglycemia occurs in such patients, it may be prolonged and appropriate management should be instituted.

Renal Impairment

Pharmacokinetics not evaluated in patients with varying degrees of renal impairment. Limited data indicate that glipizide biotransformation products may remain in circulation for a longer time in subjects with renal impairment than seen in normal renal function.

Common Adverse Effects

Most common adverse effects (>3%): Dizziness, diarrhea, nervousness, tremor, hypoglycemia, flatulence.

Drug Interactions

Protein-bound Drugs

Because glipizide is highly protein bound, it theoretically could be displaced from binding sites by, or could displace from binding sites, other protein-bound drugs such as oral anticoagulants, hydantoins, salicylate and other NSAIAs, and sulfonamides. Protein binding of glipizide is nonionic; consequently, glipizide may be less likely to be displaced from binding sites by, or displace from binding sites, other highly protein-bound drugs whose protein binding is ionic in nature.

Patients receiving highly protein-bound drugs should be observed for adverse effects when glipizide is initiated or discontinued and vice versa.

Drugs That May Alter the Hypoglycemic Effect of Sulfonylureas

Several drugs may enhance the hypoglycemic effect of sulfonylurea antidiabetic agents, including glipizide. When these drugs are administered or discontinued in patients receiving glipizide, monitor closely for hypoglycemia or loss of glycemic control, respectively.

Several drugs may decrease the hypoglycemic effect of sulfonylurea antidiabetic agents, including glipizide. When these drugs are administered or discontinued in patients receiving glipizide, monitor closely for loss of glycemic control or hypoglycemia, respectively.

Specific Drugs

Glipizide Pharmacokinetics

Absorption

Bioavailability

Rapidly and essentially completely absorbed from GI tract.

Absolute oral bioavailability: 80—100%.

Biphasic peak serum concentrations may occur, suggesting enterohepatic circulation.

Onset

Peak plasma concentration: 1—3 hours (range: 1—6 hours).

Onset of hypoglycemic action (fasting state): 15—30 minutes, maximal within 1—2 hours.

Duration

Hypoglycemic action may persist for up to 24 hours.

Food

Peak plasma concentration delayed 20—40 minutes when administered in fasting state compared to nonfasting state.

Special Populations

Glipizide concentrations may be increased in renal or hepatic insufficiency.

Distribution

Extent

Distributed into bile; very small amounts distributed into erythrocytes and saliva.

Unknown if distributed into human milk.

Plasma Protein Binding

92—99%; principally nonionic.

Elimination

Metabolism

Almost completely metabolized in liver.

Elimination Route

Excreted principally in the urine (60—90%) as unchanged drug and metabolites within 24—72 hours. Less than 10% excreted as unchanged drug.

Also excreted in feces (5—20%), almost completely via biliary elimination.

Half-life

Glipizide: 3—4.7 hours (range: 2—7.3 hours).

Glipizide metabolites: 2—6 hours.

Special Populations

Half-life of metabolites prolonged to greater than 20 hours in impaired renal function; however, glipizide metabolites largely considered inactive.

Pharmacokinetics and/or pharmacodynamics may be altered in hepatic impairment.

Renal excretion and terminal elimination half-life of metabolites substantially decreased and increased, respectively, in severe renal impairment.

No differences in pharmacokinetics observed in geriatric patients compared with younger subjects.

Stability

Storage

Oral

Tablets

Store at 20—25°C in a tight, light-resistant container.

Tablets, extended release

Store at 20—25°C (excursions permitted to 15—30°C) protected from moisture and humidity.

Actions

• Precise mechanism of hypoglycemic action unknown; appears to lower blood glucose principally by binding to the sulfonylurea receptor in the pancreatic beta cell plasma membrane, leading to closure of ATP-sensitive potassium channels and simulating the release of insulin.

• Also appears to enhance peripheral insulin action at postreceptor (probably intracellular) site(s) during short term therapy.

• Ineffective in absence of functioning beta cells.

• During prolonged administration, extrapancreatic effects appear to substantially contribute to hypoglycemic action; principal effects appear to include enhanced peripheral sensitivity to insulin and reduction of basal hepatic glucose production.

• On a weight basis, glipizide is one of the most potent sulfonylurea agents.

Advice to Patients

• Advise patients to read the FDA-approved patient labeling (Patient Information).

• Inform patients of the potential risks (including potential adverse effects) and advantages of glipizide and of alternative therapies.

• When glipizide is used in fixed combination with other drugs, inform patients of other precautionary information about the concomitant agent(s).

• Advise patients that glipizide immediate-release tablets should be taken approximately 30 minutes before a meal.

• Advise patients that glipizide extended-release tablets should be taken with breakfast or the first main meal of the day and that the tablets should be taken whole and should not be chewed, crushed, or divided. Inform patients taking glipizide extended-release tablets that they may occasionally notice something that looks like a tablet in their stool.

• Inform patients that during periods of stress (e.g., fever, trauma, infection, or surgery), a loss of glycemic control may occur. Inform patients that at such times, it may be necessary to discontinue glipizide and administer insulin.

• Educate patients and responsible family members on how to recognize and manage hypoglycemia. Advise patients and responsible family members on the risks of hypoglycemia, symptoms and treatment, and conditions that predispose to its development.

• Inform patients of the importance of adherence to dietary instructions, regular physical activity, periodic blood glucose monitoring and glycosylated hemoglobin (hemoglobin A_1c; HbA_1c) testing, recognition and management of hypoglycemia and hyperglycemia, and assessment of diabetes mellitus complications.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

• Advise patients to inform their clinician if they are or plan to become pregnant or breast-feed. Advise women who breast-feed of the need to monitor the breast-fed infant for signs of hypoglycemia (e.g., jitters, cyanosis, hypothermia, excessive sleepiness, poor feeding, seizures).

• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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