Brand names: DiaBeta, Glynase
Drug class: Sulfonylureas
VA class: HS502
Chemical name: 1-[[p-[2-(5-Chloro-o-anisamido)ethyl]phenyl]sulfonyl]-3-cyclohexylurea
Molecular formula: C₂₃H₂₈ClN₃O₅S
CAS number: 10238-21-8

Medically reviewed by Drugs.com on Jun 12, 2023. Written by ASHP.

Introduction

Antidiabetic agent; sulfonylurea.

Uses for Glyburide

Type 2 Diabetes Mellitus

Used alone or in fixed combination with metformin as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus.

Used in combination with one or more other oral antidiabetic agents or insulin as an adjunct to diet and exercise in patients who do not achieve adequate glycemic control with diet, exercise, and oral antidiabetic agent monotherapy.

Current guidelines for the treatment of type 2 diabetes mellitus generally recommend metformin as first-line therapy in addition to lifestyle modifications in patients with recent-onset type 2 diabetes mellitus or mild hyperglycemia because of its well-established safety and efficacy (i.e., beneficial effects on glycosylated hemoglobin [hemoglobin A_1c; HbA_1c], weight, and cardiovascular mortality).

In patients with metformin contraindications or intolerance (e.g., risk of lactic acidosis, GI intolerance) or in selected other patients, some experts suggest that initial therapy with a drug from another class of antidiabetic agents (e.g., a glucagon-like peptide-1 [GLP-1] receptor agonist, sodium-glucose cotransporter 2 [SGLT2] inhibitor, dipeptidyl peptidase-4 [DPP-4] inhibitor, sulfonylurea, thiazolidinedione, basal insulin) may be acceptable based on patient factors.

May need to initiate therapy with 2 agents (e.g., metformin plus another drug) in patients with high initial HbA_1c (>7.5% or ≥1.5% above target). In such patients with metformin intolerance, some experts suggest initiation of therapy with 2 drugs from other antidiabetic drug classes with complementary mechanisms of action.

Consider early initiation of combination therapy for the treatment of type 2 diabetes mellitus to extend the time to treatment failure and more rapidly attain glycemic goals.

For patients with inadequate glycemic control on metformin monotherapy, consider patient comorbidities (e.g., atherosclerotic cardiovascular disease [ASCVD], established kidney disease, heart failure), hypoglycemia risk, impact on weight, cost, risk of adverse effects, and patient preferences when selecting additional antidiabetic agents for combination therapy.

Consider early introduction of insulin for severe hyperglycemia (e.g., blood glucose of ≥300 mg/dL or HbA_1c >9–10%), especially if accompanied by catabolic manifestations (e.g., weight loss, hypertriglyceridemia, ketosis) or symptoms of hyperglycemia.

Glyburide Dosage and Administration

General

• Adjust dosage according to patient’s tolerance and fasting blood glucose determinations. Monitor HbA_1c to determine minimum effective dosage and to detect primary or secondary failure.

• During transfer from insulin therapy, patients should test their blood for glucose and their urine for glucose and/or ketones at least 3 times daily. Persistent ketonuria with glycosuria, ketosis, and/or inadequate lowering or persistent elevation of blood glucose concentration during transfer from insulin indicate that the patient requires insulin therapy.

• Micronized formulations arenotbioequivalent with conventional formulations; retitrate dosage when transferring patients from micronized to conventional formulations, or vice versa.

Administration

Oral Administration

Administer conventional or micronized formulations once daily with breakfast or first main meal. May administer in 2 divided doses in some patients (i.e., those receiving >10 mg daily [as conventional formulations] or >6 mg daily [as micronized glyburide]).

Administer fixed combination with metformin hydrochloride once or twice daily with meals.

Administer glyburide at least 4 hours prior to colesevelam when drugs given concomitantly. (See Specific Drugs under Interactions.)

Dosage

Adults

Type 2 Diabetes Mellitus

Initial Dosage in Previously Untreated Patients

Oral

Conventional formulations: Initially, 2.5–5 mg daily.

Micronized formulations: Initially, 1.5 –3 mg daily.

Fixed combination with metformin hydrochloride: Initially, 1.25 mg of glyburide and 250 mg of metformin hydrochloride once or twice daily.

Initial Dosage in Patients Transferred from Other Oral Antidiabetic Agents

Oral

Conventional formulations: Initially, 2.5–5 mg daily.

Micronized formulations: Initially, 1.5–3 mg daily.

May discontinue most other oral hypoglycemic agents (except chlorpropamide [no longer commercially available in the US]) immediately. During transfer from chlorpropamide (a drug with a long elimination half-life), monitor closely for hypoglycemia during initial 2 weeks of transition period.

Fixed combination with metformin hydrochloride: Initially, glyburide 2.5 mg/metformin hydrochloride 500 mg or glyburide 5 mg/metformin hydrochloride 500 mg twice daily in patients not adequately controlled on monotherapy with glyburide (or another sulfonylurea) or metformin. For patients previously receiving combination therapy with glyburide (or another sulfonylurea) and metformin, initial dosage should not exceed previous individual dosages of glyburide (or equivalent dosage of another sulfonylurea) and metformin.

Initial Dosage in Patients Transferred from Insulin

Oral

Conventional formulations: Initially, 2.5–5 mg once daily (if insulin dosage is <20 units daily) or 5 mg once daily (if insulin dosage is 20–40 units daily); may discontinue insulin immediately. If insulin dosage is >40 units daily, reduce insulin dosage by 50% and initiate glyburide at 5 mg daily; withdraw insulin gradually and increase glyburide dosage in increments of 1.25–2.5 mg daily every 2–10 days.

Micronized formulations: Initially, 1.5–3 mg once daily (if insulin dosage is <20 units daily) or 3 mg once daily (if insulin dosage is 20–40 units daily); may discontinue insulin immediately. If insulin dosage is >40 units daily, reduce insulin dosage by 50% and initiate glyburide at 3 mg daily; withdraw insulin gradually and increase glyburide dosage in increments of 0.75–1.5 mg daily every 2–10 days.

Titration and Maintenance Dosage

Oral

Conventional formulations: Increase dosage in increments of ≤2.5 mg daily at weekly intervals. Usual maintenance dosage is 1.25–20 mg daily.

Micronized formulations: Increase dosage in increments of ≤1.5 mg daily at weekly intervals. Usual maintenance dosage is 0.75–12 mg daily.

Fixed combination with metformin hydrochloride: Titrate dosage gradually based on glycemic control and tolerability up to a maximum daily dosage of 20 mg of glyburide and 2 g of metformin hydrochloride.

Prescribing Limits

Adults

Conventional formulations: Maximum 20 mg daily.

Micronized formulations: Maximum 12 mg daily.

Fixed combination with metformin hydrochloride: Maximum 20 mg of glyburide and 2 g of metformin hydrochloride daily.

Special Populations

Hepatic Impairment

Conventional formulations: Initially, 1.25 mg daily.

Micronized formulations: Initially, 0.75 mg daily.

Renal Impairment

Conventional formulations: Initially, 1.25 mg daily.

Micronized formulations: Initially, 0.75 mg daily.

Geriatric Patients

Conventional formulations: Initially, 1.25 mg daily

Micronized formulations: Initially, 0.75 mg daily.

Fixed combination with metformin hydrochloride: Use a lower dosage when initiating or increasing therapy.

Other Populations

Cautious dosing recommended in debilitated or malnourished patients or in patients with adrenal or pituitary insufficiency.

Conventional formulations: Initially, 1.25 mg daily

Micronized formulations: Initially, 0.75 mg daily.

Cautions for Glyburide

Contraindications

• Known hypersensitivity to glyburide or any ingredient in the formulation.

• Diabetic ketoacidosis, with or without coma.

• Type 1 diabetes mellitus.

• Concomitant bosentan therapy.

Warnings/Precautions

Warnings

Cardiovascular Effects

Increased cardiovascular mortality reported with some sulfonylurea antidiabetic agents (i.e., tolbutamide, phenformin). However, the American Diabetes Association considers the benefits of intensive glycemic control with insulin or sulfonylureas to outweigh the risks overall.

Sensitivity Reactions

Dermatologic and Sensitivity Reactions

Possible allergic skin reaction (e.g., pruritus, erythema, urticaria, morbilliform or maculopapular eruptions). Discontinue the drug if allergic reaction persists.

Angioedema, arthralgia, myalgia, and vasculitis reported.

General Precautions

Hypoglycemia

Severe, occasionally fatal, hypoglycemia reported. Debilitated, malnourished, or geriatric patients and patients with renal or hepatic impairment or adrenal or pituitary insufficiency may be particularly susceptible. Strenuous exercise, alcohol ingestion, insufficient caloric intake, or use in combination with other antidiabetic agents may increase risk. Hypoglycemia may be difficult to recognize in geriatric patients or in those receiving β-adrenergic blocking agents. (See Interactions.)

Loss of Blood Glucose Control

Possible loss of glycemic control during periods of stress (e.g., fever, trauma, infection, surgery).

Temporary discontinuance of glyburide and administration of insulin may be required.

Hematologic Effects

Hemolytic anemia may develop in patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency who receive sulfonylureas; consider a nonsulfonylurea antidiabetic agent in patients with G6PD deficiency.

Macrovascular Outcomes

Manufacturer states that no clinical studies have conclusively established macrovascular risk reduction with glyburide or any other antidiabetic drug.

Use of Fixed Combinations

When used in fixed combination with metformin hydrochloride, consider the cautions, precautions, and contraindications associated with metformin.

Specific Populations

Pregnancy

Category B.

Many experts recommend that insulin be used during pregnancy.

Lactation

Not known whether glyburide is distributed into milk; discontinue nursing or the drug.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

Increased risk of hypoglycemia; hypoglycemia may be difficult to recognize. Cautious dosing recommended. See Geriatric Patients under Dosage and Administration.

Hepatic Impairment

Increased risk of hypoglycemia. Cautious dosing recommended. (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Increased risk of hypoglycemia. Cautious dosing recommended. (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

With conventional and micronized formulations, nausea, epigastric fullness, heartburn.

With fixed-combination glyburide/metformin hydrochloride preparation, diarrhea, headache, nausea/vomiting, abdominal pain, dizziness.

Drug Interactions

When using fixed-combination preparation containing metformin hydrochloride, also consider the drug interactions associated with metformin.

Drugs Affecting Hepatic Microsomal Enzymes

Glyburide principally metabolized by CYP2C9. Consider potential interactions with CYP2C9 inducers or inhibitors.

Protein-bound Drugs

Potential pharmacokinetic interaction and possible potentiation of hypoglycemic effects when used concomitantly with other highly protein-bound drugs.

Observe for adverse effects when glyburide therapy is initiated or discontinued and vice versa.

Specific Drugs

Glyburide Pharmacokinetics

Absorption

Bioavailability

Almost completely absorbed following oral administration.

Conventional and micronized glyburide preparations not bioequivalent. (See General under Dosage and Administration.)

Onset

Hypoglycemic action generally begins within 45–60 minutes and is maximal within 1.5–3 hours.

Duration

In single-dose studies in fasting healthy individuals, the degree and duration of blood-glucose lowering is proportional to glyburide dose and AUC.

In nonfasting diabetic patients, the hypoglycemic action may persist for up to 24 hours.

Food

Food does not affect rate or extent of absorption.

Special Populations

In patients with renal or hepatic impairment, serum concentrations may be increased.

Distribution

Extent

Distributed in substantial amounts into bile.

Appears to cross the placenta. Not known if distributed into breast milk.

Plasma Protein Binding

>99% (for glyburide).

>97% (for major metabolite 4-trans-hydroxyglyburide).

Elimination

Metabolism

Appears to be completely metabolized, probably in the liver.

Elimination Route

Excreted as metabolites in urine and feces in approximately equal proportions.

Minimally removed by hemodialysis.

Half-life

1.4–1.8 hours (for glyburide) or approximately 10 hours (for glyburide and metabolites).

Special Populations

In patients with severe renal impairment, clearance may be decreased and half-life prolonged.

Stability

Storage

Oral

Conventional or Micronized Preparations

Generally, well-closed containers at 20–25°C (may be exposed to 15–30°C); consult specific labeling.

Glyburide/Metformin Hydrochloride Fixed-combination Preparations

Light-resistant containers up to 25°C.

Actions

• Stimulates secretion of endogenous insulin from beta cells of the pancreas. Lowers blood glucose concentration in diabetic and nondiabetic individuals.

• During prolonged administration, extrapancreatic effects (e.g., enhanced peripheral sensitivity to insulin, reduction of basal hepatic glucose production) contribute to the hypoglycemic action.

Advice to Patients

• Importance of regular clinical and laboratory evaluations, including urine and/or fasting blood glucose determinations.

• Importance of adhering to diet and exercise regimen.

• Risks of hypoglycemia, the symptoms and treatment of hypoglycemic reactions, and conditions that predispose to the development of hypoglycemic reactions.

• Understanding of primary and secondary failure to oral sulfonylurea antidiabetic agents.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

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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