Glyburide

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
Brands: DiaBeta, Glucovance, Glycron, Glynase, Micronase

Introduction

Antidiabetic agent; sulfonylurea.^{1 2 3 4}

Uses for Glyburide

Diabetes Mellitus

Used alone or in fixed combination with metformin as an adjunct to diet and exercise for the management of type 2 (noninsulin-dependent) diabetes mellitus in patients whose hyperglycemia cannot be controlled by diet alone.^{1 2 3 4 49 50 51 52 53 54 55 56 57 58 59 60 158}

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.^{1 124 126 158 162 165 166 168 169 170 195 196 197 198 199 200 201 202 203}

Alternative therapy in some type 2 diabetic patients being treated with insulin.^{1 2 3} Useful in combination with insulin therapy to improve glycemic control and/or decrease insulin dosage in some type 2 diabetic patients.^{116 117 118 119 120 162 165 166 168 169 170}

Not effective as sole therapy for patients with type 1 diabetes mellitus; ^{1 3 60} insulin is necessary.^{1 2 60}

Not effective as sole therapy in patients with diabetes mellitus complicated by acidosis, ketosis, or coma; insulin is necessary.^{1 2 3}

Glyburide Dosage and Administration

General

• 
  

  Adjust dosage according to patient’s tolerance and urine and/or fasting blood glucose determinations.^{1 2} Monitor glycosylated hemoglobin (hemoglobin A_1c, HbA_1c) to determine minimum effective dosage and to detect primary or secondary failure.^{1 2}

  
  


• 
  

  During transfer from insulin therapy, patients should test their blood for glucose ^{2 60 106} and their urine for glucose and/or ketones at least 3 times daily.^{1 2 124 126} Persistent ketonuria with glycosuria, ^{1 2} ketosis, ⁸⁶ and/or inadequate lowering or persistent elevation of blood glucose concentration ⁸⁶ during transfer from insulin indicate the need for insulin therapy.^{1 2 86}

  
  


• 
  

  Micronized formulations are not bioequivalent with conventional formulations; retitrate dosage when transferring patients from micronized to conventional formulations, or vice versa.¹²⁴

  
  

Administration

Oral Administration

Administer conventional or micronized formulations once daily with breakfast or first main meal.^{1 2 3 124} May administer in 2 divided doses in some patients (i.e., those receiving >10 mg daily [as conventional formulations]^{1 2} or >6 mg [as micronized glyburide]).^b

Administer fixed combination with metformin hydrochloride once or twice daily with a meal.¹⁵⁸

Dosage

Adults

Diabetes Mellitus

Initial Dosage in Previously Untreated Patients

Oral

Conventional formulations: Initially, 2.5–5 mg daily.^{1 2}

Micronized formulations: Initially, 1.5 –3 mg daily.¹²⁴

Fixed combination with metformin hydrochloride: Initially, 1.25 mg of glyburide and 250 mg of metformin hydrochloride once daily.¹⁵⁸ For severe hyperglycemia (baseline HbA_1c >9% or fasting blood glucose >200 mg/dL), 1.25 mg of glyburide and 250 mg of metformin hydrochloride twice daily, given with the morning and evening meals.¹⁵⁸

Initial Dosage in Patients Transferred from Other Oral Antidiabetic Agents

Oral

Conventional formulations: Initially, 2.5–5 mg daily.^{1 2}

Micronized formulations: Initially, 1.5–3 mg daily.¹²⁴

May discontinue most other oral hypoglycemic agents (except chlorpropamide) immediately.^{1 2 3 96 b} During transfer from chlorpropamide (a drug with a long elimination half-life), monitor closely for hypoglycemia during initial 2 weeks of transition period.^{1 2 b}

Fixed combination with metformin hydrochloride: Initially, 2.5 or 5 mg of glyburide and 500 mg of metformin hydrochloride twice daily with morning and evening meals in patients not adequately controlled by monotherapy with glyburide (or another sulfonylurea) or metformin.¹⁵⁸ 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.¹⁵⁸ Titrate in increments ≤5 mg of glyburide and 500 mg of metformin hydrochloride to achieve adequate blood glucose control.¹⁵⁸

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.^{1 2 96} 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.^{1 2}

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.^{124 b} 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.^b

Titration and Maintenance Dosage

Oral

Conventional formulations: Increase dosage in increments of ≤2.5 mg daily at weekly intervals.^{1 2} Usual maintenance dosage is 1.25–20 mg daily.^{1 2 96}

Micronized formulations: Increase dosage in increments of ≤1.5 mg daily at weekly intervals.^b Usual maintenance dosage is 0.75–12 mg daily.¹²⁴

Fixed combination with metformin hydrochloride: Titrate in increments of 1.25 mg of glyburide and 250 mg of metformin hydrochloride daily at 2-week intervals to achieve adequate blood glucose control.¹⁵⁸

Prescribing Limits

Adults

Conventional formulations: Maximum 20 mg daily.^{1 2 96}

Micronized formulations: Maximum 12 mg daily.^b

Fixed combination with metformin hydrochloride: Maximum 20 mg of glyburide and 2 g of metformin hydrochloride daily.¹⁵⁸

Special Populations

Hepatic Impairment

Conventional formulations: Initially, 1.25 mg daily.^{1 2}

Micronized formulations: Initially, 0.75 mg daily.¹²⁴

Renal Impairment

Conventional formulations: Initially, 1.25 mg daily.^{1 2}

Micronized formulations: Initially, 0.75 mg daily.¹²⁴

Geriatric Patients

Conventional formulations: Initially, 1.25 mg daily^{1 2}

Micronized formulations: Initially, 0.75 mg daily.¹²⁴

Fixed combination with metformin hydrochloride: Do not titrate to maximum recommended dosage.¹⁵⁸

Other Populations

Cautious dosing recommended in debilitated or malnourished patients or in patients with adrenal or pituitary insufficiency.^{1 2 124 158}

Conventional formulations: Initially, 1.25 mg daily^{1 2}

Micronized formulations: Initially, 0.75 mg daily.¹²⁴

Fixed combination with metformin hydrochloride: Do not titrate to maximum recommended dosage.¹⁵⁸

Cautions for Glyburide

Contraindications

• 
  

  Known hypersensitivity to glyburide or any ingredient in the formulation.^{1 2 158}

  
  


• 
  

  Diabetic ketoacidosis, with or without coma.^{1 2 3}

  
  


• 
  

  Monotherapy for type 1 diabetes mellitus.^{1 a}

  
  

Warnings/Precautions

Warnings

Cardiovascular Effects

Increased cardiovascular mortality reported with other sulfonylurea antidiabetic agents (i.e., tolbutamide, phenformin).^{1 2 63} However, the American Diabetes Association considers the benefits of intensive glycemic control with insulin or sulfonylureas to outweigh the risks overall.^{128 130 131 138 144}

Sensitivity Reactions

Dermatologic and Sensitivity Reactions

Possible allergic skin reaction (e.g., pruritus, erythema, urticaria, morbilliform or maculopapular eruptions).^{1 2} Discontinue the drug if allergic reaction persists.^{1 2}

Angioedema, arthralgia, myalgia, and vasculitis reported.¹²³

General Precautions

Hypoglycemia

Severe,^{1 2 67 68 69 74 105} occasionally fatal,^{67 68 74 105} hypoglycemia reported. Debilitated, malnourished, or geriatric patients and patients with renal or hepatic impairment or adrenal or pituitary insufficiency may be particularly susceptible.^{1 105 158} Strenuous exercise, alcohol ingestion, insufficient caloric intake, or use in combination with other antidiabetic agents may increase risk.^{1 2 96 105} Hypoglycemia may be difficult to recognize in geriatric patients or in those receiving β-adrenergic blocking agents.^{1 105 158} (See Interactions.)

Concurrent Illness

Possible loss of glycemic control during periods of stress (e.g., fever, trauma, infection, surgery).^{1 2}

Temporary discontinuance of glyburide and administration of insulin may be required.^{1 2}

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.¹

Many experts recommend that insulin be used during pregnancy.^{1 2 106}

Lactation

Not known whether glyburide is distributed into milk; discontinue nursing or the drug.^{1 2}

Pediatric Use

Safety and efficacy not established.^{1 2}

Geriatric Use

Increased risk of hypoglycemia; hypoglycemia may be difficult to recognize.^{1 105 158} Cautious dosing recommended.^{1 2 124 158} See Geriatric Patients under Dosage and Administration.

Hepatic Impairment

Increased risk of hypoglycemia.^{1 2 96 105 106} Cautious dosing recommended.^{1 2 124 158} (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Increased risk of hypoglycemia.^{1 2 96 105 106} Cautious dosing recommended.^{1 2 124 158} (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

With conventional and micronized formulations, nausea, epigastric fullness, heartburn.^{1 2 3 62}

With fixed-combination glyburide/metformin hydrochloride preparation, upper respiratory tract infection, diarrhea, headache, nausea/vomiting, abdominal pain, dizziness.¹⁵⁸

Interactions for Glyburide

When using fixed-combination preparation containing metformin hydrochloride, consider the drug interactions associated with metformin.¹⁵⁸

Protein-bound Drugs

Potential pharmacokinetic interaction and possible potentiation of hypoglycemic effects when used concomitantly with other highly protein-bound drugs.^{1 2 37 38 39 40 62 85}

Observe for adverse effects when glyburide therapy is initiated or discontinued and vice versa.^{1 2}

Specific Drugs

Drug	Interaction	Comments
Alcohol	Possible disulfiram-like reactions1 2 87
Anticoagulants, oral	Possible displacement from plasma proteins and potentiation of hypoglycemic effects1 2 37 38 39 40 62 85	Observe for adverse effects when glyburide or oral anticoagulants are initiated or discontinued1 2
Antifungals, oral (i.e., fluconazole, miconazole)	Increased glyburide concentrations; possible hypoglycemia1 124 158 210 211
β-Adrenergic blocking agents	Impaired glucose tolerance60 62 85 or potentiation of hypoglycemic effects60 62 85	If concomitantly therapy is necessary, a β1-selective adrenergic blocking agent may be preferred62
Calcium-channel blocking agents	May exacerbate diabetes mellitus1 2 90	Observe carefully for loss of glycemic control or for hypoglycemia when calcium-channel blocking agents are discontinued1 124 158
Chloramphenicol	Potentiation of hypoglycemic effects1 2 60 62 85	Observe carefully for hypoglycemic effects or loss of glycemic control when chloramphenicol is discontinued1 124 158
Contraceptives, oral	May exacerbate diabetes mellitus1 2 62 85	Observe carefully for loss of glycemic or for hypoglycemia when oral contraceptives are discontinued1 124 158
Corticosteroids	May exacerbate diabetes mellitus1 2 62 85	Observe carefully for loss of glycemic control or for hypoglycemia when corticosteroids are discontinued1 124 158
Diuretics	May exacerbate diabetes mellitus1 2 62 85	Observe carefully for loss of glycemic control or for hypoglycemia when diuretics are discontinued1 124 158
Estrogens	May exacerbate diabetes mellitus1 2 62	Observe carefully for loss of glycemic control or for hypoglycemia when estrogens are discontinued1 124 158
Fluoroquinolone anti-infectives	Potentiation of hypoglycemic effects1 2 126	Observe carefully for hypoglycemic effects or loss of glycemic control when fluoroquinolone anti-infectives are discontinued1 124 158
Hydantoins	Possible displacement from plasma protein and potentiation of hypoglycemic effects1 2 37 38 39 40 62 85	Observe for adverse effects when glyburide or hydantoins are initiated or discontinued1 2
Isoniazid	May exacerbate diabetes mellitus1 2	Observe carefully for loss of glycemic control or for hypoglycemia when isoniazid is discontinued1 124 158
MAO inhibitors	Potentiation of hypoglycemic effects1 2 62 85	Observe closely for hypoglycemic effects of loss of glycemic control when MAO inhibitors are discontinued1 124 158
Niacin	May exacerbate diabetes mellitus1 2 62	Observe carefully for loss of glycemic control or for hypoglycemia when nicotonic acid is discontinued1 124 158
NSAIAs	Possible displacement from plasma proteins and potentiation of hypoglycemic effects1 2 37 38 39 40 62 85	Observe for adverse effects when glyburide or NSAIAs are initiated or discontinued1 2
Phenothiazines	May exacerbate diabetes mellitus1 2 62 85	Observe carefully for loss of glycemic control or for hypoglycemia when phenothiazines are discontinued1 124 158
Phenylbutazone	Potentiation of hypoglycemic effects84	Monitor blood glucose control; adjust glyburide dosage when phenylbutazone is initiated or discontinued85
Phenytoin	May exacerbate diabetes mellitus1 2 62	Observe carefully for loss of glycemic control or for hypoglycemia when phenytoin is discontinued1 124 158
Probenecid	Potentiation of hypoglycemic effects1 2 62	Observe closely for hypoglycemic effects or loss of glycemic control when probencid is discontinued1 124 158
Rifampin	May exacerbate diabetes mellitus62 85	Observe carefully for loss of glycemic control or for hypoglycemia when rifampin is discontinued1 124 158
Sulfonamides	Possible displacement from plasma proteins and potentiation of hypoglycemic effects1 2 37 38 39 40 62 85	Observe for adverse effects when glyburide or sulfonamides are initiated or discontinued1 2
Sympathomimetic agents	May exacerbate diabetes mellitus1 2 62	Observe carefully for loss of glycemic control or for hypoglycemia when sympathomimetic agents are discontinued1 124 158
Thyroid agents	May exacerbate diabetes mellitus1 2 62 85	Observe carefully for loss of glycemic control or for hypoglycemia when thyroid agents are discontinued1 124 158

Glyburide Pharmacokinetics

Absorption

Bioavailability

Almost completely absorbed following oral administration.^{4 23 24 94}

Onset

Hypoglycemic action generally begins within 45–60 minutes and is maximal within 1.5–3 hours.^{4 27 32 49}

Duration

In nonfasting diabetic patients, the hypoglycemic action may persist for up to 24 hours.^{1 2 33}

Food

Food does not affect rate or extent of absorption.^{27 28 94}

Special Populations

In patients with renal^{1 2 27} or hepatic^{1 2} impairment, serum concentrations may be increased.

Distribution

Extent

Distributed in substantial amounts into bile.^{1 2 3 25 26 36}

Appears to cross the placenta.^{81 101} Not known if distributed into breast milk.^{1 2}

Plasma Protein Binding

>99% (for glyburide).^{7 25 37}

>97% (for major metabolite 4-trans-hydroxyglyburide).²⁵

Elimination

Metabolism

Appears to be completely metabolized, ^{25 26 31 36} probably in the liver.³¹

Elimination Route

Excreted as metabolites in urine and feces in approximately equal proportions.^{1 2 23 25 26 30 31 47}

Minimally removed by hemodialysis.⁴²

Half-life

1.4–1.8 hours (for glyburide)^{24 27 29 41 97} or approximately 10 hours (for glyburide and metabolites).^{25 30 31 32}

Special Populations

In patients with severe renal impairment, clearance may be decreased and half-life prolonged.^{42 43}

Stability

Storage

Oral

Conventional or Micronized Tablets

Well-closed containers at 15–30°C.^{1 2 124 126}

Fixed-combination Tablets

Light-resistant containers up to 25°C.¹⁵⁸

ActionsActions

• 
  

  Stimulates secretion of endogenous insulin from beta cells of the pancreas.^{1 2 3 4 8 9 10 11 12} Lowers blood glucose concentration in diabetic and nondiabetic individuals.^{3 4 8 9 10 11}

  
  


• 
  

  During prolonged administration, extrapancreatic effects (e.g., enhanced peripheral sensitivity to insulin, reduction of basal hepatic glucose production) contribute to the hypoglycemic action.^{4 8 9 10 11 12 15 16 17 110 111 112 121}

  
  

Advice to Patients

• 
  

  Importance of regular clinical and laboratory evaluations, including urine and/or fasting blood glucose determinations.^{1 2}

  
  


• 
  

  Importance of adhering to diet and exercise regimen.^{1 2}

  
  


• 
  

  Risks of hypoglycemia, the symptoms and treatment of hypoglycemic reactions, and conditions that predispose to the development of hypoglycemic reactions.¹

  
  


• 
  

  Understanding of primary and secondary failure to oral sulfonylurea antidiabetic agents.¹

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.¹

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

  
  


• 
  

  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.

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

Glyburide

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	1.25 mg*	DiaBeta (scored)	Sanofi-Aventis
			Glyburide Tablets	Greenstone, Sandoz, Teva
			Micronase (scored)	Pfizer
		2.5 mg*	DiaBeta (scored)	Sanofi-Aventis
			Glyburide Tablets	Greenstone, Sandoz, Teva
			Micronase (scored)	Pfizer
		5 mg*	DiaBeta (scored)	Sanofi-Aventis
			Glyburide Tablets	Greenstone, Sandoz, Teva
			Micronase (scored)	Pfizer
	Tablets (micronized)	1.5 mg*	Glyburide Micronized Tablets	Amide, Greenstone, Mylan, Stada, Teva, West-Ward
			Glycron (scored)	Zoetica
			Glynase PresTab (scored)	Pfizer
		3 mg*	Glyburide Micronized Tablets	Amide, Greenstone, Mylan, Stada, Teva, West-Ward
			Glycron (scored)	Zoetica
			Glynase PresTab (scored)	Pfizer
		4.5 mg*	Glycron (scored)	Zoetica
		6 mg*	Glyburide Micronized Tablets	Amide, Greenstone, Mylan, Stada, Teva, West-Ward
			Glycron (scored)	Zoetica
			Glynase PresTab (scored)	Pfizer

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

Glyburide Combinations

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, film-coated	1.25 mg with Metformin Hydrochloride 250 mg*	Glucovance (with povidone)	Bristol-Myers Squibb
			Glyburide with Metformin Hydrochloride Tablets	Actavis, Par, Sandoz, Teva
		2.5 mg with Metformin Hydrochloride 500 mg*	Glucovance (with povidone)	Bristol-Myers Squibb
			Glyburide with Metformin Hydrochloride Tablets	Actavis, Par, Sandoz, Teva
		5 mg with Metformin Hydrochloride 500 mg*	Glucovance (with povidone)	Bristol-Myers Squibb
			Glyburide with Metformin Hydrochloride Tablets	Actavis, Par, Sandoz, Teva

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Diabeta 1.25MG Tablets (SANOFI-AVENTIS U.S.): 50/$23.99 or 100/$45.97

Diabeta 2.5MG Tablets (SANOFI-AVENTIS U.S.): 30/$25.99 or 60/$49.97

Diabeta 5MG Tablets (SANOFI-AVENTIS U.S.): 30/$42.36 or 90/$117.67

Glucovance 2.5-500MG Tablets (B-M SQUIBB U.S. (PRIMARY CARE)): 60/$85.99 or 180/$249.98

Glucovance 5-500MG Tablets (B-M SQUIBB U.S. (PRIMARY CARE)): 60/$92 or 180/$246.06

GlyBURIDE 1.25MG Tablets (TEVA PHARMACEUTICALS USA): 30/$15.99 or 60/$23.98

GlyBURIDE 5MG Tablets (TEVA PHARMACEUTICALS USA): 30/$18.99 or 60/$29.98

GlyBURIDE Micronized 1.5MG Tablets (DAVA PHARMACEUTICALS): 90/$26.99 or 180/$52.97

GlyBURIDE Micronized 3MG Tablets (DAVA PHARMACEUTICALS): 90/$15.01 or 180/$17.99

GlyBURIDE Micronized 6MG Tablets (DAVA PHARMACEUTICALS): 90/$17 or 180/$21

GlyBURIDE-MetFORMIN 2.5-500MG Tablets (IVAX PHARMACEUTICALS INC.): 60/$45.99 or 180/$125.96

GlyBURIDE-MetFORMIN 5-500MG Tablets (TEVA PHARMACEUTICALS USA): 100/$83.99 or 300/$246.97

Glynase 1.5MG Tablets (PFIZER U.S.): 60/$53.99 or 180/$147.97

Glynase 3MG Tablets (PFIZER U.S.): 60/$75.99 or 180/$227.98

Glynase 6MG Tablets (PFIZER U.S.): 60/$129.99 or 180/$369.98

Micronase 1.25MG Tablets (PFIZER U.S.): 30/$22.99 or 90/$68.97

Micronase 2.5MG Tablets (PFIZER U.S.): 30/$28.99 or 90/$86.97

Micronase 5MG Tablets (PFIZER U.S.): 30/$41.99 or 90/$114.96

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions June 2006. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Pharmacia & Upjohn Company. Micronase (glyburide) prescribing information. Kalamazoo, MI; 2002 Mar.

2. Hoechst-Roussel Pharmaceuticals Inc. Diaβeta (glyburide) prescribing information. Somerville, NJ; 1987 Dec.

3. Anon. Glibenclamide: a review. Drugs. 1971; 1:116-40. [PubMed 5004340]

4. Jackson JE, Bressler R. Clinical pharmacology of sulphonylurea hypoglycaemic agents: part 1. Drugs. 1981; 22:211-45. [IDIS 140932] [PubMed 7021124]

5. Vomel VW, Sauer W. Zur Frage einer antimikrobiellen Wirkung des neuen oralen Antidiabeticums HB 419. (German; with English abstract) Arzneim-Forsch. 1969; 19:1491-4.

6. The British pharmacopoeia. London: Her Majesty’s Stationery Office; 1980:210.

7. Hadju VP, Kohler KF, Schmidt FH et al. Physikalisch-chemische und analytische Unter suchungen an HB 419. (German; with English abstract) Arzneim-Forsch. 1969; 19:1381-6.

8. Skillman TG, Feldman JM. The pharmacology of sulfonylureas. Am J Med. 1981; 70:361-72. [IDIS 164995] [PubMed 6781341]

9. Kolterman OG, Gray RS, Shapiro G et al. The acute and chronic effects of sulfonylurea therapy in type II diabetic subjects. Diabetes. 1984; 33:346-54. [IDIS 184146] [PubMed 6423429]

10. Duckworth WC, Solomon SS, Kitabchi AE. Effect of chronic sulfonylurea therapy on plasma insulin and proinsulin levels. J Clin Endocrinol Metab. 1972; 35:585-91. [IDIS 28916] [PubMed 5052977]

11. Feldman JM, Lebovitz HE. Endocrine and metabolic effects of glybenclamide: evidence for an extrapancreatic mechanism of action. Diabetes. 1971; 20:745-55.

12. DeFronzo RA, Ferrannini E, Koivisto V. New concepts in the pathogenesis and treatment of noninsulin-dependent diabetes mellitus. Am J Med. 1983; 74(Suppl 1A):52-81. [IDIS 164138] [PubMed 6337486]

13. Lockwood DH, Maloff BL, Nowak SM et al. Extrapancreatic effects of sulfonylureas: potentiation of insulin action through post-binding mechanisms. Am J Med. 1983; 74(Suppl 1A):102-8. [PubMed 6401922]

14. Brogden RN, Heel RC, Pakes GE et al. Glipizide: a review of its pharmacological properties and therapeutic use. Drugs. 1979; 18:329-53. [IDIS 107972] [PubMed 389600]

15. Kolterman OG, Prince MJ, Olefsky JM. Insulin resistance in noninsulin-dependent diabetes mellitus: impact of sulfonylurea agents in vivo and in vitro. Am J Med. 1983; 74(Suppl 1A):82-101. [IDIS 164139] [PubMed 6401923]

16. Beck-Nielsen H, Pedersen O, Lindskov HO. Increased insulin sensitivity and cellular insulin binding in obese diabetics following treatment with glibenclamide. Acta Endocrinol. 1979; 90:451-62. [PubMed 106617]

17. Hjollund E, Richelsen B, Beck-Nielsen H et al. The effect of glibenclamide on insulin receptors in normal man: comparative studies of insulin binding to monocytes and erythrocytes. J Clin Endocrinol Metab. 1983; 57:1257-62. [IDIS 178711] [PubMed 6415086]

18. Moses AM, Howanitz J, Miller M. Diuretic action of three sulfonylurea drugs. Ann Intern Med. 1973; 78:541