Glipizide

Class: Sulfonylureas
VA Class: HS502
Chemical Name: 1-cyclohexyl-3-[[p-[2-(5-methylpyrazine-carboxamido)ethyl]phenyl]sulfonyl]urea
Molecular Formula: C₂₁H₂₇N₅O₄S
CAS Number: 29094-61-9
Brands: Glucotrol, Glucotrol XL, Metaglip

Introduction

Antidiabetic agent; sulfonylurea.^{1 2 3}

Uses for Glipizide

Diabetes Mellitus

Used alone or in fixed combination with metformin as an adjunct to diet for the management of type 2 diabetes mellitus (noninsulin-dependent) in patients whose hyperglycemia cannot be controlled by diet alone.^{1 2 3 19 27 50 51 52 53 54 55 56 57 58 59 60 95}

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.^{95 120 127 128 129 130 139 154 155 157 158 161 159 160 161 162 164}

Alternative therapy in some type 2 diabetic patients being treated with insulin.^{1 2 52 54} Useful in combination with insulin therapy to improve glycemic control and/or decrease insulin dosage in some type 2 diabetic patients.^{2 67}

Not effective as sole therapy for patients with type 1 diabetes mellitus; insulin is necessary.

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

Glipizide Dosage and Administration

General

• 
  

  Adjust dosage according to tolerance and urine and/or fasting blood glucose determinations.¹ Monitor glycosylated hemoglobin (hemoglobin A_1c, HbA_1c) to determine minimum effective dosage or detect primary or secondary failure.^{1 95 153}

  
  

Administration

Oral Administration

Administer extended-release or conventional tablets once daily, generally with breakfast.^{1 95 1} Administer conventional tablets approximately 30 minutes before a meal.^{1 11 32}

Administer glipizide in fixed combination with metformin once daily with a meal.¹⁵³

Some patients may have a more satisfactory response when conventional oral tablets are administered in 2 or 3 divided doses daily.^{1 2 11 44 50 51 52 53 54 57 58 59 60} When dosage exceeds 15 mg daily as conventional tablets, administer in divided doses before meals of sufficient caloric content.^{1 2 59}

Extended-release tablets should be swallowed whole and should not be divided, chewed, or crushed.⁹⁵

Dosage

Adults

Diabetes Mellitus

Initial Dosage in Previously Untreated Patients

Oral

Conventional or extended-release tablets: Initially, 5 mg daily.^{1 95} Titrate dosage of conventional tablets in increments of 2.5–5 mg daily at intervals of at least several days¹ (usually 3–7 days).^{2 51 54 59 60} Maximum once daily dosage, 15 mg.¹

For extended-release tablets, dosage adjustment should be based on at least 2 similar consecutive fasting glucose concentrations obtained at least 7 days after the previous dose adjustment.⁹⁵

Initial Dosage in Patients Transferred from Conventional to Extended-release Tablets

Oral

When transferring, administer the nearest equivalent total daily dosage once daily.⁹⁵ Alternatively, 5 mg once daily as extended-release tablets and titrate dosage.⁹⁵

Initial Dosage in Patients Transferred from Other Oral Antidiabetic Agents

Oral

Individualize initial dosage of glipizide; usually 5–10 mg daily.^{90 92} The other oral antidiabetic agent may be discontinued abruptly.^{1 95}

Patients being transferred from a sulfonylurea agent with a longer half life (e.g., chlorpropamide) should be closely monitored for the occurrence of hypoglycemia during the initial 1–2 weeks.^{1 95} A drug-free interval of 2–3 days may be advisable before glipizide therapy is initiated as conventional tablets in patients being transferred from chlorpropamide, particularly if blood glucose concentration was adequately controlled with chlorpropamide.^{90 92}

Initial Dosage in Patients Transferred from Insulin

Oral

Initially, 5 mg once daily, if insulin requirements were ≤20 units daily.¹ Abruptly discontinue insulin.¹

5 mg once daily if insulin requirements were >20 units daily, and reduce insulin dosage by 50%.¹ Withdraw insulin gradually and adjust glipizide dosage in increments of 2.5–5 mg daily at intervals of at least several days.¹

Maintenance Dosage

Oral

Maintenance dosage varies considerably, ranging from 2.5–40 mg daily.^{1 2 7 27 39 40 41 42 43 44 50 51 52 53 54 56 57 58 59 60} Most patients require 5–25 mg daily as conventional tablets^{27 39 40 41 42 43 44 50 51 52 53 54 56 57 58 59 60} or 5–10 mg daily as extended-release tablets, but higher dosages may be necessary.^{7 25 95}

Combination Therapy with Other Oral Antidiabetic Agents

Oral

When added to therapy with other antidiabetic agents, the glipizide extended-release tablets may be initiated at a dosage of 5 mg daily.⁹⁵ Base titration on clinical judgment.⁹⁵

Fixed combination: 2.5 mg of glipizide and 250 mg of metformin hydrochloride once daily with a meal in treatment-naive patients.¹⁵³

For more severe hyperglycemia (i.e., fasting plasma glucose concentrations of 280–320 mg/dL), 2.5 mg of glipizide and 500 mg of metformin hydrochloride twice daily.¹⁵³

Dosage may be increased in increments of one tablet¹⁵³ (using the tablet strength at which therapy was initiated, either 2.5 mg glipizide/250 mg metformin hydrochloride or 2.5 mg glipizide/500 mg metformin hydrochloride)¹⁶³ daily every 2 weeks until the minimum effective dosage required to achieve adequate glycemic control is reached.¹⁵³

Maximum daily dosage, 10 mg of glipizide and 2 g of metformin hydrochloride.¹⁵³

In previously treated patients with inadequate glycemic control with monotherapy, 2.5 or 5 mg of glipizide and 500 mg of metformin hydrochloride twice daily with the morning and evening meals.¹⁵³

The initial dosage of the fixed combination should not exceed the daily dosage of glipizide or metformin hydrochloride previously received.¹⁵³

Titrate upward in increments not exceeding 5 mg of glipizide and 500 mg of metformin hydrochloride until adequate glycemic control is reached.¹⁵³

Maximum daily dosage, 20 mg of glipizide and 2 g of metformin hydrochloride in previously treated patients.¹⁵³

For patients previouly receiving both glipizide (or another sulfonylurea antidiabetic agent) and metformin, the initial dosage of the fixed-combination preparation should not exceed the daily dosages of glipizide (or equivalent dosage of another sulfonylurea) and metformin hydrochloride currently being taken.^{153 158} Such patients should be monitored for signs and symptoms of hypoglycemia following the switch.¹⁵³ In the transfer, the decision to switch to the nearest equivalent dosage or to titrate dosage is based on clinical judgment.¹⁵³

Prescribing Limits

Adults

Diabetes Mellitus

Oral

Maximum once-daily dose as conventional tablets is 15 mg.¹

Maximum total daily dosage is 40 mg as divided doses of conventional tablets or 20 mg as extended-release tablets.^{1 95}

Maximum daily dosage of the fixed combination, 10 mg of glipizide and 2 g of metformin hydrochloride.¹⁵³

Special Populations

Hepatic Impairment

Conventional tablets: Initially, 2.5 mg daily;¹ conservative maintenance dosage.¹

Extended-release tablets: Use conservative initial and maintenance dosage.¹

Adjust dosage carefully.^{1 27 71}

Generally, do not use in patients with severe hepatic impairment.^{2 65 72}

Renal Impairment

Use conservative initial and maintenance dosage.^{1 95}

Use generally not recommended in patients with severe renal impairment.^{2 65 72}

Cautious dosing recommended.

Geriatric Patients

Conventional tablets: Initially, 2.5 mg daily.¹

Initially, 5 mg (extended-release tablets) may be used.^{1 95}

Use conservative initial and maintenance dosage of glipizide-containing formulations.^{1 95 153}

Adjust dosage carefully.¹ Any dosage adjustment of glipizide in fixed combination with metformin hydrochloride requires careful assessment of renal function.¹⁵³

Dosage of glipizide and metformin hydrochloride in fixed combination should not be titrated to the maximum dosage.

Debilitated or Malnourished Patients

Conservative initial and maintenance dosage of conventional and extended-release tablets.^{1 95}

Dosage of glipizide and metformin hydrochloride in fixed combination should not be titrated to the maximum dosage.¹⁵³

Cautions for Glipizide

Contraindications

• 
  

  Known hypersensitivity to glipizide or any ingredient in the formulation.¹

  
  


• 
  

  Diabetes mellitus complicated by acidosis, ketosis, or coma; use of insulin is necessary.^{1 2}

  
  


• 
  

  Monotherapy for type 1 diabetes mellitus.

  
  

Warnings/Precautions

Warnings

Cardiovascular Effects

Possible increased cardiovascular mortality reported with other sulfonylurea antidiabetic agents (i.e., tolbutamide or phenformin).^{1 75} However, the American Diabetes Association considers the benefits of intensive glycemic control with insulin or sulfonylureas to outweigh the risks overall.^{97 107 113}

General Precautions

Hypoglycemia

Reported infrequently; usually mild;^{2 27 50 58 59 60} Possible severe hypoglycemia, especially geriatric patients, malnourished patients, and those with adrenal, pituitary, hepatic, or renal insufficiency.^{1 27 70 71} Strenuous exercise, alcohol ingestion, insufficient caloric intake, or use in combination with other antidiabetic agents may increase risk.¹

Appropriate patient selection and careful attention to dosage are important to avoid glipizide-induced hypoglycemia.

Concurrent Illness

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

Temporary discontinuance of glipizide and administration of insulin may be required.¹

GI Disease

Use extended-release tablets with caution in patients with severe preexisting GI narrowing, since obstruction may occur.⁹⁵

Use of Fixed Combinations

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

Specific Populations

Pregnancy

Category C.¹

Many experts recommend that insulin be used during pregnancy.^{1 95}

Lactation

Not known whether glipizide is distributed into milk;¹ discontinue nursing or the drug.¹

Pediatric Use

Safety and efficacy not established.¹ However, the ADA states that use may be considered in children with type 2 diabetes mellitus because of greater compliance and convenience and lack of evidence demonstrating better efficacy of insulin for type 2 diabetes mellitus.¹¹⁷

Geriatric Use

Increased risk of hypoglycemia.^{1 27 71} Cautious dosing recommended.^{1 27 71}

Hepatic Impairment

Increased risk of hypoglycemia.^{1 27 71} Cautious dosing recommended.^{1 27 71} (See Hepatic Impairment under Dosage and Administration.)

Generally, not recommended in severe impairment.^{2 65 72}

Renal Impairment

Increased risk of hypoglycemia.^{1 27 71} Cautious dosing recommended.^{1 27 71} (See Renal Impairment under Dosage and Administration.)

Generally, not recommended in severe impairment.^{2 65 72}

Common Adverse Effects

With conventional tablets, nausea,^{1 50} anorexia,⁵⁰ vomiting,⁵⁰ pyrosis,⁵⁰ gastralgia,¹ diarrhea,¹ and constipation.^{1 2 50}

With extended-release tablets, asthenia, headache, pain, dizziness, nervousness, tremor, diarrhea, hypoglycemia, and flatulence.⁹⁵ With glipizide in fixed combination with metformin hydrochloride, upper respiratory tract infection, diarrhea, dizziness, hypertension, nausea/vomiting, musculoskeletal pain, headache, abdominal pain, and urinary tract infection.¹⁵³

Interactions for Glipizide

Protein-bound Drugs

Potential pharmacokinetic interaction with other protein-bound drugs.^{1 2 47 72 80}

Use with caution with protein-bound drugs.¹

Specific Drugs

Drug	Interaction	Comments
Alcohol	Rarely, disulfiram like reactions1
Antifungals	Increased plasma concentrations of glipizide and hypoglycemic effect95
Anticoagulants, oral	Glipizide could displace or be displaced by oral anticoagulants from plasma protein binding sites1 2 47 72 80	Use with caution with protein-bound drugs1
β-Adrenergic blocking agents	Impaired glucose tolerance; increased frequency or severity of hypoglycemia and hypoglycemia-induced complications62 72 80	If concomitant therapy is necessary, a β1-selective adrenergic blocking agent may be preferred62 72
Calcium-channel blocking agents	May exacerbate diabetes mellitus1	Observe closely when concurrent therapy is initiated or discontinued1
Chloramphenicol	Increases hypoglycemic effect1 2 62 72 80	Observe closely when concurrent therapy is initiated or discontinued1
Cimetidine	Inhibits the hepatic metabolism of glipizide and potentiate hypoglycemic effect83	Glipizide dosage adjustment may be necessary when cimetidine therapy is initated or discontinued83
Contraceptives, oral	May exacerbate diabetes mellitus1 72 80	Observe closely when concurrent therapy is initiated or discontinued1
Corticosteroids	May exacerbate diabetes mellitus1 72 80	Observe closely when concurrent therapy is initiated or discontinued1
Dicumarol	Does not displace dicumarol from plasma protein binding sites1 81 82	Use with caution with protein-bound drugs1
Diuretics, nonthiazide	May exacerbate diabetes mellitus1 72 80	Observe closely when concurrent therapy is initiated or discontinued1
Diuretics, thiazide	May exacerbate diabetes mellitus72 80 84	Increased antidiabetic requirements72 80 84
Estrogens	May exacerbate diabetes mellitus1 72	Observe closely when concurrent therapy is initiated or discontinued1
Hydantoins	Glipizide could displace or be displaced by hydantoins from plasma protein binding sites1 2 47 72 80	Use with caution with protein-bound drugs1
Indoprofen	Does not displace indoprofen from plasma protein binding sites1 81 82	Use with caution with protein-bound drugs1
Isoniazid	May exacerbate diabetes mellitus1	Observe closely when concurrent therapy is initiated or discontinued1
MAO inhibitors	Increases hypoglycemic effects1 2 72 80	Observe closely when concurrent therapy is initiated or discontinued1
Niacin	May exacerbate diabetes mellitus1	Observe closely when concurrent therapy is initiated or discontinued1
NSAIAs	Glipizide could displace or be displaced by nonsteroidal anti-inflammatory agents from plasma protein binding sites1 2 47 72 80	Use with caution with protein-bound drugs1
Phenothiazines	May exacerbate diabetes mellitus1 72 80	Observe closely when concurrent therapy is initiated or discontinued1
Phenytoin	May exacerbate diabetes mellitus1 72 72	Observe closely when concurrent therapy is initiated or discontinued1
Probenecid	Increases hypoglycemic effects1 72 80	Observe closely when concurrent therapy is initiated or discontinued1
Rifampin	May exacerbate diabetes mellitus72 80	Observe closely when concurrent therapy is initiated or discontinued1
Salicylate	Does not displace salicylate from plasma protein binding sites1 81 82	Use with caution with protein-bound drugs1
Sulfonamides	Glipizide could displace or be displaced by sulfonamides from plasma protein binding sites1 2 47 72 80	Use with caution with protein-bound drugs1
Sympathomimetic agents	May exacerbate diabetes mellitus1 72	Observe closely when concurrent therapy is initiated or discontinued1
Thyroid agents	May exacerbate diabetes mellitus1 72 80	Observe closely when concurrent therapy is initiated or discontinued1

Glipizide Pharmacokinetics

Absorption

Bioavailability

Absorption is essentially complete; ^{1 30 31 32 33 34 35 36 37 38} 80–100% of an oral dose may be absorbed.^{30 31 95}

Onset

15–30 minutes.^{6 32 33}

Duration

In nonfasting diabetic patients, the hypoglycemic action may persist for up to 24 hours.^{1 39 40 41 42 43 44}

Food

Food delays the absorption of conventional tablets but does not affect peak serum concentrations achieved or the extent of absorption of the drug.^{32 33} Peak serum concentrations following administration of conventional tablets generally are delayed 20–40 minutes in the nonfasting state compared with the fasting state.^{1 32 33}

Peak plasma concentrations of glipizide following adminsitration in fixed combination with metformin hydrochloride with food are delayed by 1 hour.¹⁵³

Food does not affect the glycemic response or the time to absorption of extended-release tablets.⁹⁵ Peak blood concentrations following administation of extended-release tablets and food are increased.⁹⁵

Distribution

Extent

Following IV administration in mice, distributed into the liver and blood, with lower concentrations in the lungs, kidneys, adrenals, myocardium, salivary glands, and retroscapular fat.⁴⁵ In humans, small amounts of glipizide are apparently distributed into bile^{30 34 37} and very small amounts are distributed into erythrocytes and saliva.³⁰

Not known if glipizide is distributed into milk.¹

Plasma Protein Binding

92–99%.^{30 34 36 46 95}

Elimination

Metabolism

Appears to be almost completely metabolized, ^{30 34 35 36 37} mainly in the liver.¹

Elimination Route

Glipizide and its metabolites are excreted principally in urine^{30 34 35 36 37} (60–90%) and to a lesser extent in feces (5–20%).^{30 34 35 37 95}

⁹⁵

Half-life

Terminal elimination half-life of glipizide averages 3–4.7 hours following oral administration in patients with normal renal and hepatic function.^{9 30 31 32 33 34 35 38 39 48}

Terminal elimination half-life of total glipizide metabolites ranges from 2–6 hours.³⁷

Special Populations

Renal or hepatic impairment may increase serum glipizide concentrations and reduce elimination.^{1 37}

Severe renal impairment may decrease the renal excretion of and increase the terminal elimination half-life of glipizide metabolites.³⁷

Stability

Storage

Oral

Tablets (conventional)

Tight, light-resistant containers⁹⁰ at a temperature <30°C.¹

Tablets (extended-release)

15–30°C; protect from moisture and humidity.⁹⁵

Tablets (fixed-combination)

20–25°C (may be exposed to 15–30°C).¹⁵³

ActionsActions

• 
  

  Sulfonylurea antidiabetic agent.^{1 2 3}

  
  


• 
  

  Lowers blood glucose concentration in diabetic and nondiabetic individuals.^{2 3 5 6 7 8 9 10 11 12 13}

  
  


• 
  

  Stimulates secretion of postprandial endogenous insulin from the beta cells of the pancreas.^{1 2 3 5 7 8 9 10 11 12 13}

  
  


• 
  

  During prolonged administration, extrapancreatic effects such as enhanced peripheral sensitivity to insulin and reduction of basal hepatic glucose production contribute to the hypoglycemic action.^{3 5 7 8 10 12 13 14 16 17 23 24}

  
  

Advice to Patients

• 
  

  Importance of regular clinical and laboratory evaluations, including blood and urine glucose determinations.¹

  
  


• 
  

  Importance of adherence to diet and exercise regimen.¹

  
  


• 
  

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

  
  


• 
  

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

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.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

Glipizide

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	5 mg*	Glipizide Tablets	Apotex, Mylan, Sandoz, Teva, Watson
			Glucotrol (scored)	Pfizer
		10 mg*	Glipizide Tablets	Apotex, Mylan, Sandoz, Teva, Watson
			Glucotrol (scored)	Pfizer
	Tablets, extended-release	2.5 mg*	Glipizide Tablets ER	Andrx, Greenstone
			Glucotrol XL	Pfizer
		5 mg*	Glipizide Tablets ER	Andrx, Greenstone, Watson
			Glucotrol XL	Pfizer
		10 mg*	Glipizide Tablets ER	Andrx, Greenstone, Watson
			Glucotrol XL	Pfizer

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

Glipizide Combinations

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, film-coated	2.5 mg with 250 mg Metformin Hydrochloride*	Glipizide with Metformin Hydrochloride Tablets	CorePharma, Sandoz, Teva
			Metaglip	Bristol-Myers Squibb
		2.5 mg with 500 mg Meformin Hydrochloride*	Glipizide with Metformin Hydrochloride Tablets	CorePharma, Sandoz, Teva
			Metaglip	Bristol-Myers Squibb
		5 mg with 500 mg Metformin Hydrochloride*	Glipizide with Metformin Hydrochloride Tablets	CorePharma, Sandoz, Teva
			Metaglip	Bristol-Myers Squibb

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.

GlipiZIDE 10MG 24-hr Tablets (WATSON LABS): 30/$19.99 or 90/$59.97

GlipiZIDE 10MG Tablets (WATSON LABS): 90/$19.5 or 180/$21.99

GlipiZIDE 5MG Tablets (WATSON LABS): 100/$22.42 or 200/$23.65

GlipiZIDE XL 2.5MG 24-hr Tablets (GREENSTONE): 30/$18.99 or 60/$26.98

GlipiZIDE XL 5MG 24-hr Tablets (GREENSTONE): 30/$15.99 or 90/$34.98

Glucotrol 10MG Tablets (PFIZER U.S.): 60/$79.86 or 180/$219.9

Glucotrol 5MG Tablets (PFIZER U.S.): 60/$49.99 or 180/$125.96

Glucotrol XL 10MG 24-hr Tablets (PFIZER U.S.): 30/$48.99 or 90/$122.97

Glucotrol XL 2.5MG 24-hr Tablets (PFIZER U.S.): 30/$31.99 or 90/$72.97

Glucotrol XL 5MG 24-hr Tablets (PFIZER U.S.): 30/$31.99 or 90/$72.97

Metaglip 2.5-250MG Tablets (B-M SQUIBB U.S. (PRIMARY CARE)): 30/$33.99 or 90/$97.97

Metaglip 5-500MG Tablets (B-M SQUIBB U.S. (PRIMARY CARE)): 30/$42.99 or 90/$109.97

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. Pfizer. Glucotrol (glipizide) tablets prescribing information. New York, NY; 2000 Oct.

2. 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]

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

4. Reynolds JEF, ed. Martindale: the extra pharmacopoeia. 28th ed. London: The Pharmaceutical Press; 1982:855.

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

6. Pisani Ceretti A, Losi S, Orsini G et al. A controlled study of the hypoglycemic and insulinopoietic effect of glipizide and glibenclamide in non-diabetic human subjects. Arzneimittelforschung. 1975; 25:675-6. [IDIS 185762] [PubMed 808231]

7. Greenfield MS, Doberne L, Rosenthal M et al. Effect of sulfonylurea treatment on in vivo insulin secretion and action in patients with non-insulin-dependent diabetes mellitus. Diabetes Care. 1982; 31:307-12.

8. Reaven GM. Effect of glipizide treatment on various aspects of glucose, insulin, and lipid metabolism in patients with noninsulin-dependent diabetes mellitus. Am J Med. 1983; 75(Suppl. 5B):8-14. [IDIS 180370] [PubMed 6369970]

9. Peterson CM, Sims RV, Jones RL et al. Bioavailability of glipizide and its effect on blood glucose and insulin levels in patients with non-insulin-dependent diabetes. Diabetes Care. 1982; 5:497-500. [PubMed 6765225]

10. Lebovitz HE, Feinglos MN. Mechanism of action of the second-generation sulfonylurea glipizide. Am J Med. 1983; 75(Suppl. 5B):46-54. [IDIS 180373] [PubMed 6369967]

11. Sartor G, Scherstén B, Melander A. Effects of glipizide and food intake on the blood levels of glucose and insulin in diabetic patients. Acta Med Scand. 1978; 203:211-4. [PubMed 345754]

12. Feinglos MN, Lebovitz HE. Sulfonylurea treatment of insulin-independent diabetes mellitus. Metabolism. 1980; 29:488-94. [PubMed 6990184]

13. Lebovitz HE, Feinglos MN, Bucholtz HK et al. Potentiation of insulin action: a probable mechanism for the anti-diabetic action of sulfonylurea drugs. J Clin Endocrinol Metab. 1977; 45:601-4. [IDIS 93603] [PubMed 903405]

14. 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]

15. Gurwich EL (The Upjohn Company, Kalamazoo, MI): Personal communication; 1984 Jun 25.

16. 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]

17. 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]

18. Larner J. Mediators of postreceptor action of insulin. Am J Med. 1983; 74(Suppl. 1A):38-51. [PubMed 6297300]

19. Fineberg SE, Schneider SH. Glipizide versus tolbutamide, an open trial: effects on insulin secretory patterns and glucose concentrations. Diabetologia. 1980; 18:49-54. [PubMed 6988265]

20. Marco J, Valverde I. Unaltered glucagon secretion after seven days of sulphonylurea administration in normal subjects. Diabe