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 (AACE/ACE [Garber 2020]; ADA 2021; ADA/EASD [Davies 2018]).
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 (DeFronzo 1999; Wexler 2021; manufacturer's labeling). 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 (Wexler 2021; manufacturer's labeling).
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) (DeFronzo 1999; Del Prato 2014; Wexler 2021; manufacturer's labeling). Note: Increasing dosage to the labeled maximum dose of 40 mg/day has not been shown to improve glycemic control (DeFronzo 1999). 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 (DeFronzo 1999; Wexler 2021; manufacturer's labeling).
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) (DeFronzo 1999; Wexler 2021; manufacturer's labeling).
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.
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) (ADA [Tuttle 2014]; KDOQI 2012); however, conservative initial and maintenance dosing is recommended to avoid hypoglycemic events (manufacturer’s labeling):
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 (Arjona Ferreira 2013a; expert opinion).
eGFR <10 mL/minute/1.73 m2: Avoid use if possible (Golightly 2013). 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 (Arjona Ferreira 2013a; Gianchandani 2017).
Hemodialysis, intermittent (thrice weekly): Not likely to be dialyzable (manufacturer’s labeling).
Dose for eGFR <10 mL/minute, use with caution (Arjona Ferreira 2013b; Gianchandani 2017).
Peritoneal dialysis: Dose for eGFR <10 mL/minute, use with caution (Gianchandani 2017; expert opinion).
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
Diabetes mellitus, type 2, treatment (alternative agent):
Note: For the treatment of type 2 diabetes in older adults, medication classes with low risk of hypoglycemia are preferred (ADA 2021); sulfonylureas are known to have a relatively high risk of hypoglycemia as compared to other noninsulin antidiabetic agents due to their mechanism of action (AACE [Garber 2020]; ADA 2021). In general, if a sulfonylurea is chosen, a shorter-duration sulfonylurea (eg, glipizide, glimepiride) is preferred (ADA 2021).
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral:
Glucotrol: 5 mg [DSC], 10 mg [DSC] [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
Yes
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
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.
Diabetes mellitus, type 2, treatment: Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
GlipiZIDE may be confused with glimepiride, glyBURIDE
Glucotrol may be confused with Glucophage, Glucotrol XL, glyBURIDE, GlycoTrol (dietary supplement)
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. 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%, postmarketing, and/or case reports: Agranulocytosis, anorexia, aplastic anemia, bloody stools, cardiac arrhythmia, chills, cholestatic jaundice, confusion, conjunctivitis, decreased libido, disulfiram-like reaction, dyspnea, dysuria, edema, eye pain, flushing, hemolytic anemia, hepatic injury, hypertension, hypertonia, hyponatremia, jaundice, leukopenia, migraine, pancytopenia, pharyngitis, porphyria, retinal hemorrhage, SIADH (syndrome of inappropriate antidiuretic hormone secretion), skin photosensitivity, thrombocytopenia, unsteady gait, vertigo
Hypersensitivity to glipizide, sulfonamide derivatives, or any component of the formulation; type 1 diabetes mellitus; diabetic ketoacidosis (with or without coma).
Note: Although glipizide extended-release (XL) 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.
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 1998), have not supported an association. In patients with established atherosclerotic cardiovascular disease (ASCVD), other agents are preferred (ADA 2021).
• 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.
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 2013). 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; 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.
Special populations:
• Debilitated or malnourished patients: Use with caution; dosing should be conservative and monitor closely for hypoglycemia.
• Elderly: Use with caution; monitor closely for hypoglycemia.
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 2021). 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).
Substrate of CYP2C9 (major), OATP1B1/1B3 (SLCO1B1/1B3); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
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. Risk C: Monitor therapy
Alpelisib: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). 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: 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. Risk C: 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. Risk C: Monitor therapy
Chloramphenicol (Systemic): May increase the serum concentration of Sulfonylureas. Risk C: Monitor therapy
Cimetidine: May increase the serum concentration of Sulfonylureas. Risk C: Monitor therapy
Clarithromycin: May enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy
Colesevelam: May decrease the serum concentration of GlipiZIDE. Management: Administer glipizide at least 4 hours prior to colesevelam. Risk D: Consider therapy modification
Cyclic Antidepressants: May enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy
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
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
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 decrease the protein binding of Sulfonylureas. 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 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
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.
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 2021; Alexopoulos 2019; Egan 2020)
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 2021; Blumer 2013).
Agents other than glipizide are currently recommended to treat diabetes mellitus in pregnancy (ADA 2021).
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 2021; 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.
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.
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 2021; KDIGO 2020).
Recommendations for glycemic control in patients with diabetes:
Nonpregnant adults with diabetes (ADA 2021):
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 (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 (more or less stringent goals may be appropriate based on patient-specific characteristics).
Older adults (≥65 years of age) (ADA 2021):
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% to 8.5% (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 (healthy); 90 to 150 mg/dL (complex/intermediate health); 100 to 180 mg/dL (very complex/poor health).
Bedtime capillary blood glucose: 80 to 180 mg/dL (healthy); 100 to 180 mg/dL (complex/intermediate health); 110 to 200 mg/dL (very complex/poor health).
Classification of hypoglycemia (ADA 2021):
Level 1: 54 to 70 mg/dL; hypoglycemia alert value; initiate fast-acting carbohydrate (eg, glucose) treatment.
Level 2: <54 mg/dL; 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.
Stimulates insulin release from the pancreatic beta cells; reduces glucose output from the liver; insulin sensitivity is increased at peripheral target sites
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%)
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)
5 mg (per each): $0.35 - $0.40
10 mg (per each): $0.60 - $0.76
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