(GLIP i zide)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Glucotrol: 5 mg, 10 mg [scored]
Generic: 5 mg, 10 mg
Tablet Extended Release 24 Hour, Oral:
GlipiZIDE XL: 2.5 mg, 5 mg, 10 mg
Glucotrol XL: 2.5 mg, 5 mg, 10 mg
Generic: 2.5 mg, 5 mg, 10 mg
Brand Names: U.S.
- GlipiZIDE XL
- Glucotrol XL
- Antidiabetic Agent, Sulfonylurea
Stimulates insulin release from the pancreatic beta cells; reduces glucose output from the liver; insulin sensitivity is increased at peripheral target sites
Immediate release: Rapid and complete; delayed with food
Hepatic via CYP2C9; forms metabolites (inactive)
Urine (<10% as unchanged drug; 80% as metabolites); feces (10%)
Time to Peak
1-3 hours; extended release tablets: 6-12 hours
Duration of Action
98% to 99%; primarily to albumin
Use: Labeled Indications
Diabetes mellitus, type 2: Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (noninsulin dependent, NIDDM).
Limitations of use: Not recommended for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis.
Hypersensitivity to glipizide, sulfonamide derivatives, or any component of the formulation; type 1 diabetes mellitus (insulin dependent, IDDM); diabetic ketoacidosis (with or without coma).
Note: Although the FDA-approved product labeling states this medication is contraindicated with other sulfonamide-containing drug classes, the scientific basis of this statement has been challenged. See Warnings/Precautions for more detail.
Documentation of allergenic cross-reactivity for sulfonylureas is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.
Diabetes mellitus, type 2: Oral:
Immediate release: Initial: 5 mg once daily; titrate in 2.5 to 5 mg increments no more frequently than every few days based on blood glucose response; if once-daily dose is ineffective, may divide the dose; doses >15 mg/day should be administered in divided doses. Maximum recommended once-daily dose: 15 mg; maximum recommended total daily dose: 40 mg (some clinicians recommend a maximum total daily dose of 20 mg [Defronzo 1999]).
Extended release: Initial: 5 mg once daily; start patients at risk for hypoglycemia at 2.5 mg; adjust dose based on glycemic control; maximum: 20 mg/day.
When transferring from immediate release to extended release glipizide: May switch the total daily dose of immediate release to the nearest equivalent daily dose of the extended release tablet and administer once daily.
When transferring from insulin to glipizide immediate release:
Current insulin requirement ≤20 units: Discontinue insulin and initiate glipizide at usual dose
Current insulin requirement >20 units: Decrease insulin by 50% and initiate glipizide at usual dose; gradually decrease insulin dose based on patient response.
Conversion from therapy with long half-life agents: Observe patient carefully for 1 to 2 weeks when converting from a longer half-life agent (eg, chlorpropamide) to glipizide due to overlapping hypoglycemic effects.
Immediate release: Initial: 2.5 mg once daily; consider titrating by 2.5 to 5 mg/day at 1- to 2-week intervals
Extended release: 2.5 mg once daily; maintenance dosing should be conservative to avoid hypoglycemia.
Dosing: Renal Impairment
There are no specific dosage adjustments provided in the manufacturer’s labeling. Glipizide is primarily converted to inactive metabolites and may be less likely to cause hypoglycemia in patients with renal impairment compared to other sulfonylureas. A reduced dose may be necessary (Alsahli 2015). Avoidance of sustained release formulation has been suggested. (Snyder 2004)
Dosing: Hepatic Impairment
Initial: 2.5 mg once daily
Patients that are NPO or require decreased caloric intake may need doses held to avoid hypoglycemia.
Extended release: Administer with breakfast or the first meal of the day; swallow tablets whole, do not chew, divide or crush.
Immediate release: Administer 30 minutes before a meal (preferably before breakfast if once-daily dosing) to achieve greatest reduction in postprandial hyperglycemia.
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.
Extended release: Store at 68°F to 77°F (20°C to 25°C); excursions permitted between 59°F to 86°F (15°C to 30°C). Protect from moisture and humidity.
Immediate release: Store below 30°C (86°F).
Ajmaline: Sulfonamides may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. Monitor therapy
Alcohol (Ethyl): Sulfonylureas may enhance the adverse/toxic effect of Alcohol (Ethyl). A flushing reaction may occur. Monitor therapy
Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy
Aminolevulinic Acid: Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid. Monitor therapy
Androgens: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Exceptions: Danazol. Monitor therapy
Antidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy
Antidiabetic Agents (Thiazolidinedione): May enhance the hypoglycemic effect of Sulfonylureas. Management: Consider sulfonylurea dose adjustments in patients taking thiazolidinediones and monitor for hypoglycemia. Consider therapy modification
Beta-Blockers: May enhance the hypoglycemic effect of Sulfonylureas. Cardioselective beta-blockers (eg, acebutolol, atenolol, metoprolol, and penbutolol) may be safer than nonselective beta-blockers. All beta-blockers appear to mask tachycardia as an initial symptom of hypoglycemia. Ophthalmic beta-blockers are probably associated with lower risk than systemic agents. Exceptions: Levobunolol; Metipranolol. Monitor therapy
Carbocisteine: Sulfonylureas may enhance the adverse/toxic effect of Carbocisteine. Specifically, sulfonylureas may enhance adverse effects of alcohol that is present in liquid formulations of carbocisteine-containing products. Monitor therapy
Ceritinib: May increase the serum concentration of CYP2C9 Substrates. Management: Concurrent use of ceritinib with a CYP2C9 substrate that has a narrow therapeutic index (e.g., warfarin, phenytoin) should be avoided when possible. Monitor therapy
Chloramphenicol: May decrease the metabolism of Sulfonylureas. Monitor therapy
Cimetidine: May increase the serum concentration of Sulfonylureas. Monitor therapy
Clarithromycin: May increase the serum concentration of GlipiZIDE. Monitor therapy
Colesevelam: May decrease the serum concentration of GlipiZIDE. Management: Administer glipizide at least 4 hours prior to colesevelam. Consider therapy modification
Cyclic Antidepressants: May enhance the hypoglycemic effect of Sulfonylureas. Monitor therapy
CYP2C9 Inducers (Strong): May increase the metabolism of CYP2C9 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
CYP2C9 Inhibitors (Moderate): May decrease the metabolism of CYP2C9 Substrates. Monitor therapy
CYP2C9 Inhibitors (Strong): May decrease the metabolism of CYP2C9 Substrates. Consider therapy modification
Dabrafenib: May decrease the serum concentration of CYP2C9 Substrates. Management: Seek alternatives to the CYP2C9 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Dexketoprofen: May enhance the adverse/toxic effect of Sulfonamides. Monitor therapy
DPP-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. Consider therapy modification
Enzalutamide: May decrease the serum concentration of CYP2C9 Substrates. Management: Concurrent use of enzalutamide with CYP2C9 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP2C9 substrate should be performed with caution and close monitoring. Consider therapy modification
Fibric Acid Derivatives: May enhance the hypoglycemic effect of Sulfonylureas. Monitor therapy
Fluconazole: May increase the serum concentration of Sulfonylureas. Management: Seek alternatives when possible. If used together, monitor closely for increased effects of sulfonylureas if fluconazole is initiated/dose increased, or decreased effects if fluconazole is discontinued/dose decreased. Consider therapy modification
GLP-1 Agonists: May enhance the hypoglycemic effect of Sulfonylureas. Management: Consider sulfonylurea dose reductions when used in combination with glucagon-like peptide-1 agonists. Avoid the use of lixisenatide in patients receiving both basal insulin and a sulfonylurea. Consider therapy modification
Herbs (Hypoglycemic Properties): May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy
Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy
Hypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Monitor therapy
Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy
Lumacaftor: May decrease the serum concentration of CYP2C9 Substrates. Lumacaftor may increase the serum concentration of CYP2C9 Substrates. Monitor therapy
MAO Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
Mecamylamine: Sulfonamides may enhance the adverse/toxic effect of Mecamylamine. Avoid combination
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. Consider therapy modification
Miconazole (Oral): May enhance the hypoglycemic effect of Sulfonylureas. Miconazole (Oral) may increase the serum concentration of Sulfonylureas. Monitor therapy
MiFEPRIStone: May increase the serum concentration of CYP2C9 Substrates. Management: Use CYP2C9 substrates at the lowest recommended dose, and monitor closely for adverse effects, during and in the 2 weeks following mifepristone treatment. Consider therapy modification
Mitiglinide: May enhance the adverse/toxic effect of Sulfonylureas. Avoid combination
Pegvisomant: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Monitor therapy
Posaconazole: May enhance the hypoglycemic effect of GlipiZIDE. Posaconazole may increase the serum concentration of GlipiZIDE. Monitor therapy
Probenecid: May decrease the protein binding of Sulfonylureas. Probenecid may increase the serum concentration of Sulfonylureas. Monitor therapy
Quinolone Antibiotics: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolone Antibiotics may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy
RaNITIdine: May increase the serum concentration of Sulfonylureas. Monitor therapy
RifAMPin: May decrease the serum concentration of Sulfonylureas. Management: Seek alternatives to these combinations when possible. Monitor closely for diminished therapeutic effects of sulfonylureas if rifampin is initiated/dose increased, or enhanced effects if rifampin is discontinued/dose decreased. Consider therapy modification
Salicylates: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
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 inhibitor and monitor patients for hypoglycemia. Consider therapy modification
Sulfonamide Derivatives: May enhance the hypoglycemic effect of Sulfonylureas. Monitor therapy
Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy
Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. 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. Monitor therapy
Voriconazole: May increase the serum concentration of Sulfonylureas. Monitor therapy
Frequency not always defined.
Cardiovascular: Syncope (<3%)
Central nervous system: Dizziness (2% to 7%), nervousness (4%), anxiety (<3%), depression (<3%), hypoesthesia (<3%), insomnia (<3%), pain (<3%), paresthesia (<3%), drowsiness (2%), headache (2%)
Dermatologic: Diaphoresis (<3%), pruritus (1% to <3%), eczema (1%), erythema (1%), maculopapular rash (1%), morbilliform rash (1%), skin rash (1%), urticaria (1%)
Endocrine & metabolic: Hypoglycemia (<3%), increased lactate dehydrogenase
Gastrointestinal: Diarrhea (1% to 5%), flatulence (3%), dyspepsia (<3%), vomiting (<3%), constipation (1% to <3%), nausea (1% to <3%), abdominal pain (1%)
Hepatic: Increased serum alkaline phosphatase, increased serum AST
Neuromuscular & skeletal: Tremor (4%), arthralgia (<3%), leg cramps (<3%), myalgia (<3%)
Ophthalmic: Blurred vision (<3%)
Renal: Increased blood urea nitrogen, increased serum creatinine
Respiratory: Rhinitis (<3%)
<1% (Limited to important or life-threatening): Agranulocytosis, anorexia, aplastic anemia, bloody stools, cardiac arrhythmia, cholestatic jaundice, conjunctivitis, disulfiram-like reaction, dyspnea, edema, hemolytic anemia, hepatic injury, hypertension, hypertonia, hyponatremia, jaundice, leukopenia, migraine, pancytopenia, porphyria, retinal hemorrhage, SIADH (syndrome of inappropriate antidiuretic hormone secretion), skin photosensitivity, thrombocytopenia, unsteady gait, vertigo
Concerns related to adverse effects:
• Cardiovascular mortality: 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 (UKPDS) have not supported an association.
• Hypoglycemia: All sulfonylurea drugs are capable of producing severe hypoglycemia. Hypoglycemia is more likely to occur when caloric intake is deficient, after severe or prolonged exercise, when ethanol is ingested, or when more than one glucose-lowering drug is used. It is also more likely in elderly or debilitated patients, malnourished patients and in patients with impaired renal or hepatic function, adrenal and/or pituitary insufficiency; use with caution. Autonomic neuropathy, advanced age, and concomitant use of beta-blockers or other sympatholytic agents may impair the patient’s ability to recognize the signs and symptoms of hypoglycemia; use with caution.
• Sulfonamide (“sulfa”) 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 sulfonamides. There is a potential for cross-reactivity between members of a specific class (eg, two antibiotic sulfonamides). However, 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 may not occur or at the very least this potential is extremely low (Brackett 2004; Johnson 2005; Slatore 2004; Tornero 2004). In particular, mechanisms of cross-reaction due to antibody production (anaphylaxis) are unlikely to occur with nonantibiotic sulfonamides. T-cell-mediated (type IV) reactions (eg, maculopapular rash) are less well understood and it is not possible to completely exclude this potential based on current insights. In cases where prior reactions were severe (Stevens-Johnson syndrome/TEN), some clinicians choose to avoid exposure to these classes.
• 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; hypoglycemia may be prolonged.
• 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.
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
• Debilitated or malnourished patients: Use with caution; dosing should be conservative and monitor closely for hypoglycemia.
• Elderly: Use with caution; dosing should be conservative and monitor closely for hypoglycemia.
• Secondary failure: Loss of efficacy may be observed following prolonged use as a result of the progression of type 2 diabetes mellitus which results in continued beta cell destruction. In patients who were previously responding to sulfonylurea therapy, consider additional factors which may be contributing to decreased efficacy (eg, inappropriate dose, nonadherence to diet and exercise regimen). If no contributing factors can be identified, consider discontinuing use of the sulfonylurea due to secondary failure of treatment. Additional antidiabetic therapy (eg, insulin) will be required.
Signs and symptoms of hypoglycemia (fatigue, excessive hunger, profuse sweating, numbness of extremities), blood glucose, hemoglobin A1c (at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; quarterly in patients not meeting treatment goals or with therapy change [ADA 2016a])
Pregnancy Risk Factor
Adverse events have been observed in some animal reproduction studies. 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.
In women with diabetes, maternal hyperglycemia can be associated with congenital malformations as well as adverse effects in the fetus, neonate, and the mother (ACOG 2005; ADA 2015; Kitzmiller 2008; Metzger 2007). 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 (ACOG 2013; ADA 2015; Blumer 2013; Kitzmiller 2008). Prior to pregnancy, effective contraception should be used until glycemic control is achieved (Kitzmiller 2008). Other agents are currently recommended to treat diabetes in pregnant women (ACOG 2013; Blumer 2013).
The manufacturer recommends if glipizide is used during pregnancy, it should be discontinued at least 1 month before the expected delivery date.
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience dizziness, diarrhea, nausea, flatulence, anxiety, or tablet shell in stool. Have patient report immediately to prescriber signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating), vision changes, slurred speech, tingling, or severe loss of strength and energy (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.