Generic Name: Repaglinide
Class: Meglitinides
ATC Class: A10BX02
VA Class: HS502
Chemical Name: (S)-2-Ethoxy-4-[2-[[methyl-1-[2-(1-piperidinyl)-phenyl]butyl]amino]-2-oxoethyl]-benzoic acid
CAS Number: 135062-02-1

Introduction

Antidiabetic agent; meglitinide derivative.2 6 8 11 12 14 56 57 59 60 61 63 65

Uses for Prandin

Diabetes Mellitus

Used as monotherapy as an adjunct to diet and exercise for the management of type 2 (noninsulin-dependent) diabetes mellitus (NIDDM) in patients whose hyperglycemia cannot be controlled by diet and exercise alone.1 5 61 65

Not effective as sole therapy in patients with diabetes mellitus complicated by acidosis, ketosis, or coma; management of these conditions requires the use of insulin.24 25 56 76

Slideshow: Flashback: FDA Drug Approvals 2013

May be used in combination with metformin or a thiazolidinedione antidiabetic agent (e.g., pioglitazone, rosiglitazone) as an adjunct to diet and exercise for the management of type 2 diabetes mellitus in patients who do not achieve adequate glycemic control with diet, exercise, and monotherapy with metformin, a sulfonylurea, repaglinide, or a thiazolidinedione antidiabetic agent.1 5 13 59 61 102

Has been used in combination with isophane (NPH) insulin to improve glycemic control in patients with type 2 diabetes mellitus who do not respond adequately to therapy with one or more oral antidiabetic agents.56 115

Prandin Dosage and Administration

General

  • Carefully individualize dosage based on patient response and tolerance.1 71 81 99

  • Goal of therapy is to reduce both fasting blood (or plasma) glucose and glycosylated hemoglobin (hemoglobin A1c [HbA1c]) values to normal or near normal using lowest effective dosage of repaglinide, either when used as monotherapy or in combination with metformin or a thiazolidinedione.1 14 71 99

  • (Glucose concentrations in plasma generally are 10–15% higher than those in whole blood; glucose concentrations also may vary according to the method and laboratory used for these determinations.)31 51

  • Monitor patients with regular laboratory evaluations, including fasting blood (or plasma) glucose determinations, to assess therapeutic response and minimum effective dosage.1 14 31 109 American Diabetes Association (ADA) and some clinicians currently suggest that routine blood glucose monitoring should include fasting and 2-hour postprandial blood glucose concentrations.40 71 109

  • May be helpful to determine postprandial blood glucose concentrations in patients whose preprandial blood glucose concentrations are satisfactory but whose overall glycemic control (as determined by glycosylated hemoglobin values) is inadequate.1 Monitoring of glucose concentrations may be useful to detect primary failure (inadequate lowering of glucose concentration at maximum recommended dosage) or secondary failure (loss of glycemic control following an initial period of effectiveness) of drug therapy.1 14 71

  • During initiation of therapy and titration of dosage, perform fasting and postprandial blood glucose determinations weekly to determine therapeutic response and minimum effective dosage of repaglinide; thereafter, glycosylated hemoglobin values should be monitored approximately every 3 months to evaluate long-term glycemic control.1 5 14 31 40 71 In patients usually well controlled by dietary management alone, short-term therapy with repaglinide may be sufficient during periods of transient loss of diabetic control.1 5 14

  • If inadequate glycemic control and/or secondary failure occurs during maintenance therapy with repaglinide, a sulfonylurea, a thiazolidinedione, or metformin alone, combined therapy with metformin or a thiazolidinedione and repaglinide may result in an adequate response.1 14 102 If secondary failure occurs with combined metformin and repaglinide therapy, most clinicians currently recommend discontinuance of oral antidiabetic agents and initiation of insulin therapy.1 14 40 However, other options include the addition of a third oral antidiabetic agent (e.g., acarbose, a thiazolidinedione) before switching to insulin therapy.40 56 59 71 (See Diabetes Mellitus under Uses.)

Transferring from Therapy with Other Antidiabetic Agents

  • Transition period generally not required when transferring from most other oral antidiabetic agents; may abruptly discontinue other oral antidiabetic agent and initiate repaglinide the day after the final dose of that drug.1 5 14

  • Exaggerated hypoglycemic response may occur in some patients during transition from a long-acting sulfonylurea antidiabetic agent (e.g., chlorpropamide) to repaglinide; may be necessary to monitor closely for hypoglycemia for one week or longer after transition.1 5 14 61 71

Concomitant Therapy with Metformin or a Thiazolidinedione

  • If adequate glycemic control (i.e., fasting blood glucose concentrations between 80 and 140 mg/dL with infrequent hypoglycemic episodes) not achieved with repaglinide monotherapy,14 31 111 may add metformin or a thiazolidinedione.1 14 27 31 36 71 May also use in combination with metformin and thiazolidinedione in patients who have inadequate glycemic control after 2–3 months with initial metformin, sulfonylurea, or thiazolidinedione monotherapy.1 14 27 31 36 40 102 109

  • Titrate initial dosage of repaglinide during combination therapy as with repaglinide monotherapy.1 14 With concomitant metformin or thiazolidinedione and repaglinide therapy, adjust dosage of each drug to obtain adequate glycemic control (as determined by fasting plasma glucose and glycosylated hemoglobin concentrations) using minimum effective dosage of each drug.1 14 Failure to titrate the dosage of each drug to the minimum effective level could result in an increased risk of hypoglycemic episodes.1 14 71

  • In patients who do not respond to 3 months of concomitant therapy at the maximum dosage of each oral antidiabetic agent, generally should discontinue therapy with oral antidiabetic agents and institute insulin therapy.1 14 27 Other options include adding a third oral antidiabetic agent (e.g., acarbose, a thiazolidinedione) before switching to insulin therapy.1 14 27 40 56 59 71 (See Diabetes Mellitus under Uses.)

Administration

Oral Administration

Generally, administer within 15 minutes of each meal but may give as early as 30 minutes prior to each meal up to immediately preceding each meal.1 59 61 71 Administration with food may affect the extent of absorption.14 59 (See Food under Pharmacokinetics.)

Pre-meal doses may enhance glycemic control compared with twice-daily dosing at breakfast and dinner using the same total daily dosage.11 71

If a meal is skipped or added, skip or add a dose, respectively, for that meal.1 5 14 59 61 62 68 71

Dosage

Adults

Diabetes Mellitus
Oral

Initially, 0.5 mg (the minimum effective dosage) preprandially 2–4 times daily (depending on meal patterns) in patients not previously treated with oral antidiabetic agents or in those who have relatively good glycemic control (i.e., glycosylated hemoglobin <8%).1 5 14 40 56 61 62 71

Patients with glycosylated hemoglobin ≥8% despite treatment with other oral antidiabetic agents: initially, 1 or 2 mg with or preceding each meal.1 5 14 61 62 71

Approximately 90% of maximal glucose-lowering effect is achieved with dosage of 1 mg 3 times daily.56 57 66

May double dosage at no less than weekly intervals until desired fasting blood glucose concentration (e.g., 80–140 mg/dL with infrequent hypoglycemic episodes) is achieved or maximum daily dosage of 16 mg (e.g., 4 mg four times daily depending on meal patterns) is attained.1 3 5 14 27 31 36 56 59 61 62 71

Safety and efficacy of higher dosages (8–20 mg 3–4 times daily before meals) not established.14 71

Prescribing Limits

Adults

Diabetes Mellitus
Oral

Maximum daily dosage of 16 mg (e.g., 4 mg four times daily depending on meal patterns) recommended by manufacturer;1 3 5 14 27 31 36 56 59 61 62 71 higher dosages have been used.14 71 (See Diabetes Mellitus under Dosage and Administration.)

Special Populations

Renal Impairment

Mild to moderate renal dysfunction: No adjustment in initial dosage necessary.1 May administer usual initial dosage but use caution with subsequent dosage increases.1 5 59 61 71 104

Severe renal impairment (e.g., Clcr 20–40 mL/minute): Initiate dosage of 0.5 mg daily and titrate carefully.1

Use not established in patients with Clcr <20 mL/minute or those with renal failure requiring hemodialysis.1

Hepatic Impairment

Use with caution.1 5 59 71 Manufacturer recommends same initial dosage used in patients with normal hepatic function, but should make subsequent dosage adjustments at longer than usual intervals (e.g., 3 months) to allow full assessment of response.1 5 59 61 71 105 Some clinicians suggest lower initial dosage in patients with hepatic impairment.64

Cautions for Prandin

Contraindications

  • Sole therapy in patients with type 1 (insulin-dependent) diabetes mellitus or in patients with diabetes complicated by acute or chronic metabolic acidosis, including diabetic ketoacidosis with or without coma.1 5 61 71

  • Known hypersensitivity to repaglinide or any ingredient in the formulation.1 61

Warnings/Precautions

General Precautions

Hypoglycemia

Potential for hypoglycemia.1 5 14 80 81 99 100 101 102 104 105 Debilitated, malnourished, or geriatric patients and those with hepatic or severe renal impairment or adrenal or pituitary insufficiency may be particularly susceptible.1 5 61 Strenuous exercise, alcohol ingestion, insufficient caloric intake, or use in combination with other antidiabetic agents may increase risk.1 5 61 71

Hypoglycemia may be difficult to recognize in geriatric patients or in those receiving β-adrenergic blocking agents.1 5 Increased risk of serious hypoglycemia in patients with hepatic failure, who may have reduced clearance of repaglinide and diminished gluconeogenic capacity.1 5 61 64

Appropriate patient selection, patient education, and careful attention to dosage are important to avoid hypoglycemic episodes.1

Loss of Glycemic Control

Possible loss of glycemic control during periods of stress (e.g., fever, trauma, infection, surgery).1 31 61 71 Temporary discontinuance of repaglinide and administration of insulin may be required.1 31 61 71 May reinstitute after the acute episode is resolved based on clinician judgment.40 71

Specific Populations

Pregnancy

Category C.1 Abnormal maternal blood glucose concentrations during pregnancy may be associated with a higher incidence of congenital abnormalities.1 31 48 71

Most experts recommend use of insulin during pregnancy.1 14 56 64 71 109

Lactation

Distributed into milk in rats; not known whether distributed into human milk.1

Discontinue nursing or the drug.1 14 71

Pediatric Use

Safety and efficacy of repaglinide in children <18 years of age not established.40 71 However, the American Diabetes Association (ADA) states that most pediatric diabetologists use oral antidiabetic agents in children with type 2 diabetes mellitus because of greater patient compliance and convenience for the patient’s family.109

Geriatric Use

Safety and efficacy appear to be similar in geriatric and younger patients except for the expected age-related increase in cardiovascular morbidity observed with repaglinide and other comparative oral antidiabetic agents.1 5 14 1 5 14 101 (See Absorption: Special Populations under Pharmacokinetics.) No increase in frequency and severity of hypoglycemia in geriatric versus younger patients receiving repaglinide.1 14 101

Individualize antidiabetic therapy when implementing strict glycemic control considering advanced age, comorbid conditions, preexisting clinically relevant microvascular and macrovascular complications or other vascular risk factors, degree of hyperglycemia, and life expectancy.31 58

Hepatic Impairment

Use with caution.1 5 59 71

Renal Impairment

Use with caution.1 5 61

Common Adverse Effects

Hypoglycemia,1 5 14 80 81 99 100 101 102 104 105 upper respiratory tract infection,1 headache,1 64 71 80 81 arthralgia,1 sinusitis,1 nausea,1 diarrhea,1 back pain.1

Interactions for Prandin

Metabolized by CYP3A4 to inactive metabolites.1

Drugs or Foods Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP3A4: potential pharmacokinetic interaction (increased repaglinide AUC and peak blood concentrations).1

Inducers of CYP3A4: potential pharmacokinetic interaction (decreased repaglinide AUC and peak blood concentrations).1 14 59 62 64 71

Close monitoring of blood glucose concentrations suggested in patients receiving concomitant CYP3A4 inhibitors or inducers.40 59 71

Protein-bound Drugs

Potential pharmacokinetic interaction with other protein-bound drugs (increased free repaglinide concentrations due to displacement from plasma protein binding sites by other drugs).1 5 14 61 64 71 104 Conversely, repaglinide could displace other protein-bound drugs from binding sites.1 14 71

Observe patient for evidence of hypoglycemia or loss of glycemic control when other protein-bound drugs are initiated or withdrawn, respectively, in patients receiving repaglinide.1 5 14 71

Specific Drugs and Foods

Drug or Food

Interaction

Comments

β-Adrenergic blocking agents

Potential for displacement of repaglinide and/or β-adrenergic blocking agents from plasma proteins1 14 71

Observe for evidence of hypoglycemia or loss of glycemic control when β-adrenergic blocker is added to therapy or withdrawn1 5 14 71

Antiretroviral agents, HIV protease inhibitors

Potential inhibition of repaglinide metabolism

Barbiturates

Potential for increased repaglinide metabolism1 14 59 62 64 71

Close monitoring of blood glucose concentrations suggested in patients receiving such concomitant therapy40 59 71

Calcium-channel blocking agents

May cause hyperglycemia and exacerbate glycemic control in patients with diabetes mellitus1 14 61 71

Observe for evidence of altered glycemic control when a calcium-channel blocker is added to therapy or discontinued1 5 14 71

Carbamezapine

Potential for increased metabolism of repaglinide1

Close monitoring of blood glucose concentrations suggested in patients receiving such concomitant therapy40 59 71

Chloramphenicol

Potential for displacement of repaglinide and/or chloramphenicol from plasma proteins1 14 71

Observe for evidence of hypoglycemia or loss of glycemic control when chloramphenicol is added to therapy or discontinued1 5 14 71

Cimetidine

No appreciable effect on repaglinide pharmacokinetics1 14 49 64 71 106

Clarithromycin

Increased AUC and peak plasma concentration of repaglinide1

May necessitate an adjustment in repaglinide dosage1

Clofibrate

May enhance the hypoglycemic effect of repaglinide71 117

Observe for evidence of altered glycemic control when clofibrate is added to therapy or discontinued 1 5 14 71

Corticosteroids

May cause hyperglycemia and exacerbate glycemic control in patients with diabetes mellitus1 14 61 71

Observe closely for evidence of altered glycemic control when corticosteroid is added to therapy or discontinued1 5 14 71

Cyclosporine

Potential inhibition of metabolism of repaglinide14 59 62 64 71

Digoxin

No clinically relevant effect on digoxin pharmacokinetics1 71

Close observation for hypoglycemia or loss or glycemic control suggested when digoxin is added to therapy or discontinued71

Diuretics (e.g., thiazides)

May cause hyperglycemia and exacerbate glycemic control in patients with diabetes mellitus1 14 61 71

Observe closely for evidence of altered glycemic control when thiazides or other diuretics are added to therapy or discontinued1 5 14 71

Erythromycin

Potential inhibition of repaglinide metabolism1 14 59 62 64 71

Estrogens

May cause hyperglycemia and exacerbate glycemic control in patients with diabetes mellitus1 14 61 71

Observe closely for evidence of altered glycemic control when estrogens are added to therapy or discontinued1 5 14 71

Furosemide

In vitro evidence that furosemide decreases the protein binding of repaglinide and increases free circulating repaglinide concentrations64

Interaction not thought to be clinically important64

Gemfibrozil

Increased AUC and plasma repaglinide concentrations and prolonged half-life; may enhance and prolong the hypoglycemic effects of repaglinide1

Should not initiate gemfibrozil therapy in patients taking repaglinide, and those taking gemfibrozil should not begin therapy with repaglinide1

Grapefruit juice

Potential inhibition of repaglinide metabolism71

HMG-CoA reductase inhibitors (statins)

Potential for displacement of repaglinide and/or certain statins from plasma proteins1 14 71

Observe closely for evidence of hypoglycemia or loss of glycemic control when certain statins added to therapy or discontinued1 5 14 71

Isoniazid

May cause hyperglycemia and may exacerbate glycemic control in patients with diabetes mellitus 1 14 61 71

Observe closely for evidence of altered glycemic control when isoniazid is added to therapy or discontinued1 5 14 71

Itraconazole

Potential increase in repaglinide AUC1

With concomitant use of gemfibrozil and itraconazole, increased AUC and prolonged half-life of repaglinide1

Patients already receiving concomitant therapy with repaglinide and gemfibrozil should not receive itraconazole1

Ketoconazole

Increased AUC and peak blood concentrations of repaglinide1

MAO inhibitors

Potential for displacement of repaglinide and/or MAO inhibitors from plasma proteins1 14 71

Observe closely for evidence of hypoglycemia or loss of glycemic control when MAO inhibitors are added to therapy or discontinued1 5 14 71

Niacin

May cause hyperglycemia and exacerbate glycemic control in patients with diabetes mellitus1 14 61 71

Observe closely for evidence of altered glycemic control when niacin is added to therapy or discontinued1 5 14 71

Nifedipine

No clinically relevant effect on nifedipine pharmacokinetics1 71

Close observation for hypoglycemia or loss or glycemic control suggested when nifedipine is added to therapy or discontinued71

NSAIAs

Potential for displacement of repaglinide and/or salicylates from plasma proteins1 14 71

When initiated or withdrawn in patients receiving repaglinide, observe for evidence of hypoglycemia or loss of glycemic control1 5 14 71

Oral contraceptives

May cause hyperglycemia and exacerbate glycemic control in patients with diabetes mellitus1 14 61 71

Increased peak concentrations of repaglinide and the oral contraceptive components with concomitant use of repaglinide and the fixed combination of levonorgestrel and ethinyl estradiol1

Increased AUC for the ethinyl estradiol component1

Observe closely for evidence of altered glycemic control when oral contraceptives are added to therapy or discontinued1 5 14 71

Phenothiazines

May cause hyperglycemia and exacerbate glycemic control in patients with diabetes mellitus 1 14 61 71

Observe closely for evidence of altered glycemic control when phenothiazines are added to therapy or discontinued1 5 14 71

Phenytoin

May cause hyperglycemia and exacerbate glycemic control in patients with diabetes mellitus1 14 61 71

Observe closely for evidence of altered glycemic control when phenytoin added to therapy or discontinued1 5 14 71

Probenecid

Potential for displacement of repaglinide and/or probenecid from plasma proteins1 14 71

Observe closely for evidence of hypoglycemia or loss of glycemic control when probenecid added to therapy or discontinued1 5 14 71

Rifampin

Decrease in rifampin AUC and peak blood concentration1

Close monitoring of blood glucose concentrations suggested in patients receiving such concomitant therapy40 59 71

Sulfonamides

Potential for displacement of repaglinide and/or sulfonamides from plasma proteins1 14 71

Observe closely for evidence of hypoglycemia or loss of glycemic control when sulfonamides are added to therapy or discontinued1 5 14 71

Sympathomimetics

May cause hyperglycemia and exacerbate glycemic control in patients with diabetes mellitus1 14 61 71

Observe closely for evidence of altered glycemic control when sympathomimetics are added to therapy or discontinued1 5 14 71

Theophylline

No clinically relevant effect on theophylline pharmacokinetics1 71

Close observation for hypoglycemia or loss of glycemic control suggested when theophylline is added to therapy or discontinued71

Thyroid preparations

May cause hyperglycemia and exacerbate glycemic control in patients with diabetes mellitus1 14 61 71

Observe closely for evidence of altered glycemic control when thyroid preparations are added to therapy or discontinued1 5 14 71

Tolbutamide

In vitro evidence that tolbutamide decreases the protein binding of repaglinide64

Interaction not thought to be clinically important64

Warfarin

In vitro evidence that warfarin decreases the protein binding of repaglinide; not thought to be clinically relevant64

Close observation for hypoglycemia or loss of glycemic control suggested when warfarin is added to therapy or discontinued1 5 14 71

Prandin Pharmacokinetics

Absorption

Bioavailability

Approximately 56% (absolute).1 5 14 61 71

Peak plasma drug concentrations attained within approximately 1 hour.1 10 14 56 59 60 61 62 64 65 68 71 100 107

Onset

Peak serum insulin concentrations achieved in approximately 1.5 hours.113 Maximum glycemic effect within 3–3.5 hours.2 61 79 Most of the hypoglycemic effect occurs within 1–3 weeks.1 5 11 14 61 65 71 80 113

Duration

Plasma insulin concentrations remain elevated for 4 hours after each meal in patients with type 2 diabetes mellitus;10 return toward premeal concentrations between meals and at bedtime.1 2 5 11 14 61 64 71

Food

Food may delay and reduce the extent of GI absorption.1 5 14 59 61 71 Administration with a high-fat meal slightly reduces peak plasma concentration and AUC but not time to peak concentration;60 61 64 reduction not clinically important.14 59

Special Populations

Greater systemic exposure (as determined by peak plasma concentrations and AUCs) to repaglinide in patients with hepatic impairment.1 5 14 61 71 105

Increases in plasma concentrations and AUC of repaglinide in patients with severe renal impairment (Clcr 20–40 mL/minute).1 5 59 60 61 64 71 104 Such alterations not found in patients with mild to moderate renal impairment.1 5 71 104

No pharmacokinetic differences (peak plasma concentration, AUC) observed in geriatric individuals (≥65 years of age) compared with healthy younger individuals.1 5 14 101

Distribution

Extent

Distributes into erythrocytes.107

Distributes into milk in rats; not known whether distributed into human milk.1 14

Plasma Protein Binding

>98%.1 5 14 61 64 71 104

Elimination

Metabolism

Rapidly metabolized by CYP3A4 to inactive metabolites.1 5 14 59 62 64 65 67 71 80 81 99 100 101 104 105 107

Elimination Route

Extensively metabolized in liver and excreted into bile and feces (90%) as metabolites.1 3 5 14 40 56 59 60 61 64 68 71 73 80 99 104 106 107

Small amount excreted in urine (8%) principally as metabolites.1 5 14 56 59 60 61 64 65 68 80 99 104 106 107

Does not appear to be removed by hemodialysis.1 104

Half-life

About 1 hour.1 3 5 14 59 61 62 64 65 68 101 107

Special Populations

In patients with hepatic impairment, elimination of unbound repaglinide reduced compared with that in healthy individuals.14 71 105

Stability

Storage

Oral

Tablets

Well-closed containers at ≤25°C; protect from moisture.1 Stable for at least 12 months in the original container at 25°C and 60% relative humidity.71

Actions

  • At least as potent as glyburide in inhibiting ATP-sensitive potassium channels, increasing intracellular concentrations of calcium, and stimulating insulin release.2 5 7 8 9 14 60 61 64 Effect on potassium and calcium channels is somewhat selective for pancreatic β-cells and does not appear to affect skeletal or cardiac muscle or thyroid tissue.1 5 14 71 80

  • Does not stimulate insulin release in the absence of glucose; insulin release diminished at low glucose concentrations.2 5 7 9 14 60 64 71 Little effect on serum insulin concentrations between meals and overnight.71

  • As blood glucose concentrations increase, augments the glucose-induced closure of ATP-sensitive potassium channels and, thereby, the release of insulin.5 8 9 58 59 60 61 63

  • Exerts most of its insulinotropic activity at intermediate glucose concentrations (54–180 mg/dL).9 60 63 At high glucose concentrations (>270 mg/dL), does not augment the insulin release already stimulated by high extracellular glucose concentrations.9 60 63

  • As with sulfonylurea antidiabetic agents, requires functioning pancreatic β-cells for hypoglycemic activity, since the drug lowers blood glucose concentrations principally by augmenting endogenous insulin secretion from the pancreas in response to a meal.1 5 14 56 57 58 59 60 61 62 64 67 71

  • Reduces fasting and postprandial blood glucose concentrations, serum fructosamine concentrations, and glycosylated hemoglobin in patients with type 2 diabetes mellitus.1 2 5 14 58 65 67 80 81

  • Does not appear to appreciably affect blood lipids (total, HDL-, or LDL-cholesterol) or fibrinogen concentrations.2 14 56 71 81 100

  • Weight gain observed in therapy-naive patients.1 14 56 64 80 100 Suggested mechanisms for increased weight include an increase in insulin secretion (which may increase appetite), stimulation of lipogenesis in fat tissue, or resistance to the actions of leptin (which decreases appetite and increases energy expenditure).13 50 56 74 111 112

Advice to Patients

  • Advise fully and completely about the nature of diabetes mellitus, how to prevent and detect complications, and control their condition.18 29 31 45 71

  • Importance of dietary regulation as principal consideration in management of diabetes mellitus.1 42 43 44 Advise that repaglinide therapy is used only as an adjunct to,1 and not a substitute for, proper dietary regulation.1 5 Advise that patients should not neglect dietary restrictions, develop a careless attitude about their condition, or disregard instructions about weight control, exercise, hygiene, and avoidance of infection.46 47

  • Inform patients of the potential risks and advantages of repaglinide therapy and of alternative forms of treatment.1 5

  • Importance of adherence to meal planning and dosing; if skipping a meal or adding an extra meal, skip or add a dose, respectively, for that meal.1 5 14 59 61 62 68 71

  • Advise that failure to follow an appropriate dosage regimen may result in hypoglycemia or hyperglycemia.14

  • Instruct patients on proper use of other antidiabetic agents, if concomitant therapy required, in order to avoid hypoglycemia.1 5

  • Inform patients of risks of hypoglycemia, symptoms and treatment of hypoglycemic reactions, and conditions that predispose to the development of such reactions.1 5 31

  • Instruct patients about the possibility of primary and secondary failure of oral antidiabetic agents.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, 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.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Repaglinide

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

0.5 mg

Prandin (with povidone)

Novo Nordisk

1 mg

Prandin (with povidone)

Novo Nordisk

2 mg

Prandin (with povidone)

Novo Nordisk

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Prandin 0.5MG Tablets (NOVO NORDISK): 30/$91.21 or 90/$263.72

Prandin 1MG Tablets (NOVO NORDISK): 30/$91.21 or 90/$263.72

Prandin 2MG Tablets (NOVO NORDISK): 90/$263.75 or 270/$759.36

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions September 1, 2005. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Novo Nordisk. Prandin (repaglinide) tablets prescribing information. Princeton, NJ; 2003 Aug.

2. Anon. Repaglinide. Drugs Future. 1996; 21: 694-9.

3. Wolffenbuttel BHR, Nijst L, Sels JPE et al. Effects of a new oral hypoglycaemic agent, repaglinide, on metabolic control in sulphonylurea-treated patients with NIDDM. Eur J Clin Pharmacol. 1993; 45: 113-6.

4. Perentesis GP, Damsbo P, Muller PG et al. Single dose pharmacokinetics and pharmacodynamics of repaglinide in type II diabetic patients. J Clin Pharmacol. 1994; 34: 1021.

5. NovoNordisk. Product information form for American hospital formulary service: Prandin (repaglinide tablets). Princeton, NJ.

6. Lins L, Brasseur R, Malaisse WJ. Conformational analysis of non-sulfonylurea hypoglycemic agents of the meglitinide family. Biochem Pharmacol. 1995; 50: 1879-84. [PubMed 8615868]

7. Gromada J, Dissing S, Kofod H et al. Effects of the hypoglycaemic drugs repaglinide and glibenclamide on ATP-sensitive potassium-channels and cytosolic calcium levels in β TC3 cells and rat pancreatic beta cells. Diabetologia. 1995; 38: 1025-32. [PubMed 8591815]

8. Malaisse WJ. Stimulation of insulin release by non-sulfonylurea hypoglycemic agents: the meglitinide family. Horm Metab Res. 1995; 27: 263-6.

9. Fuhlendorff J, Rorsman P, Kofod H et al. Stimulation of insulin release by repaglinide and glibenclamide involves both common and distinct processes. Diabetes. 1998; 47: 345-51. [PubMed 9519738]

10. Profozic V, Babic D, Renar I et al. Benzoic acid derivative hypoglycemic activity in non-insulin dependent diabetic patients. Diabetologia. 1993; 36(Suppl 1): A183.

11. Damsbo P, Andersen PH, Lund S et al. Improved glycemic control with repaglinide in NIDDM with 3 times daily meal related dosing. Abstract presented at 57th annual American Diabetes Association scientific sessions. Boston, MA, 1997 June 21–4. Abstract No. 0132.

12. Landgraf R, Bilo HJG, Müller PG. A comparison of repaglinide and glibenclamide in the treatment of type 2 diabetic patients previously treated with sulphonylureas. Eur J Clin Pharmacol. 1999; 55:165-71. [IDIS 429488] [PubMed 10379630]

13. Moses R, Carter J, Slobodniuk R et al. Effect of repaglinide addition to metformin monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care. 1999; 22:119-24. [IDIS 437593] [PubMed 10333912]

14. Novo Nordisk. Prandin (repaglinide) tablets product monograph. Princeton, NJ: 1998 Mar.

15. Roerig. Glucotrol prescribing information. In: Physicians’ desk reference. 52nd ed. Oradell, NJ: Medical Economics Company Inc; 1998:2182-3.

16. National Diabetes Data Group. Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes. 1979; 28:1039-57. [PubMed 510803]

17. American Diabetes Association. Office guide to diagnosis and classification of diabetes mellitus and other categories of glucose intolerance. Diabetes Care. 1995; 18(Suppl 1):4.

18. Williams G. Management of non-insulin-dependent diabetes mellitus. Lancet. 1994; 343:95-100. [IDIS 324190] [PubMed 7903785]

19. Genuth S. Exogenous insulin administration and cardiovascular risk in non-insulin-dependent and insulin-dependent diabetes mellitus. Ann Intern Med. 1996;124(1 Part 2):104-9.

20. Henry R R. Glucose control and insulin resistance in non-insulin-dependent diabetes mellitus. Ann Intern Med. 1996; 124:97-103. [IDIS 358776] [PubMed 8554221]

21. DeFronzo RA. The triumvirate: beta-cell, muscle, liver. A collusion responsible for NIDDM. Diabetes. 1988; 37:667-87. [PubMed 3289989]

22. Polonsky KS, Sturis J, Bell GI. Non-insulin-dependent diabetes mellitus-a genetically programmed failure of the beta cell to compensate for insulin resistance. N Engl J Med. 1996; 334:777-83. [PubMed 8592553]

23. Swislocki A. Insulin resistance and hypertension. Am J Med Sci. 1990; 300:104-15. [IDIS 272104] [PubMed 2206054]

24. Bailey C, Turner R. Metformin. N Engl J Med. 1996; 334:374-9. [IDIS 359274] [PubMed 8538710]

25. Bailey CJ. Biguanides and NIDDM. Diabetes Care. 1992; 15:755-72. [PubMed 1600835]

26. United Kingdom prospective diabetes study group. United Kingdom prospective diabetes study (UKPDS) 16: overview of 6 years’ therapy of type II diabetes: a progressive disease. Diabetes. 1995; 44:1240-58.

27. Zimmerman B, Espenshade J, Fujimoto W et al. The pharmacological treatment of hyperglycemia in NIDDM. Diabetes Care. 1995; 18:1510-18. [IDIS 355480] [PubMed 8722084]

28. Lebovitz HE. Stepwise and combination drug therapy for the treatment of NIDDM. Diabetes Care. 1994; 17:1542-4. [IDIS 340102] [PubMed 7882832]

29. Clark CM Jr. Where do we go from here? Ann Intern Med. 1996; 124(1 Part 2):184-6. Editorial.

30. Bloomgarden ZT. New and traditional treatment of glycemia in NIDDM. Diabetes Care. 1996; 19:295-9. [PubMed 8742586]

31. American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care. 2003; 26(Suppl 1):S33-50.

32. 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]

33. Zimmerman BR. Preventing long term complications: implications for combination therapy with acarbose. Drugs. 1992; 44:54-9. [PubMed 1280578]

34. Klein R, Klein BEK, Moss SE et al. Glycosylated hemoglobin predicts the incidence and progression of diabetic retinopathy. JAMA. 1988; 260:2864-71. [PubMed 3184351]

35. Ohkubo Y, Kishikawa H, Araki E et al. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin- dependent diabetes mellitus; a randomized prospective 6-year study. Diabetes Res Clin Pract. 1995; 28:103-17. [PubMed 7587918]

36. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993; 329:977-86. [IDIS 320201] [PubMed 8366922]

37. Laakso M. Glycemic control and the risk for coronary heart disease in patients with non-insulin-dependent diabetes mellitus. The Finnish studies. Ann Intern Med. 1996;124(1 Part 2):127-30.

38. Krentz AJ, Ferner RE, Bailey CJ. Comparative tolerability profiles of oral antidiabetic agents. Drug Safety. 1994; 11:223-41. [PubMed 7848543]

39. Turner R, Cull C, Holman R et al. United Kingdom Prospective Diabetes Study 17: a 9-year update of a randomized, controlled trial on the effect of improved metabolic control on complications in non-insulin-dependent diabetes mellitus. Ann Intern Med. 1996; 124(1 Pt 2):136-45. [IDIS 358782] [PubMed 8554206]

40. Reviewers’ comments (personal observations).

41. Scientific Advisory Panel of the Executive Committee, American Diabetes Association. Policy statement: the UGDP controversy. Diabetes. 1979; 28:168-70.

42. Kerr CP. Improving outcomes in diabetes: a review of the outpatient care of NIDDM patients. J Fam Pract. 1995; 40:63-75. [PubMed 7807040]

43. Anon. Diabetes mellitus. NIH Cons Dev Conf Statement. 1986; 6:1-7.

44. Blake GH. Control of type II diabetes: reaping the rewards of exercise and weight loss. Postgrad Med. 1992; 92:129-32. [PubMed 1437899]

45. Expert Committee of the Canadian Diabetes Advisory Board. Clinical practice guidelines for treatment of diabetes mellitus. CMAJ. 1992; 147:697-712. [PubMed 1521215]

46. Reviewers’ comments on metformin (personal observations).

47. Bristol-Myers Squibb, Princeton, NJ: personal communication on metformin.

48. Coretzee EJ, Jackson WPU. Pregnancy in established non-insulin-dependent diabetics. S Afr Med J. 1980; 58:795-802. [IDIS 127025] [PubMed 6777880]

49. Wanwimolruk S, Sunbhanich M, Pongmarutai M et al. Effects of cimetidine and ranitidine on the pharmacokinetics of quinine. Br J Clin Pharmacol. 1986; 22:346-50.

50. Hermann LS, Melander A. Biguanides: basic aspects and clinical use. In: Alberti KGMM, DeFronzo RA, Keen H et al, eds. International textbook of diabetes mellitus. New York: John Wiley & Sons; 1992:773-95.

51. Howanitz PJ, Howanitz JH. Carbohydrates. In: Henry JB, ed. Todd-Sanford-Davidsohn clinical diagnosis and management by laboratory methods. 17th ed. Philadelphia: W.B. Saunders Company; 1984:165-179.

52. Henry RR, Genuth S. Forum One: Current recommendations about intensification of metabolic control in non-insulin-dependent diabetes mellitus. Ann Intern Med. 1996; 124(1 Pt 2):175-7. [IDIS 358784] [PubMed 8554214]

53. Grant PJ. The effects of high- and medium-dose metformin therapy on cardiovascular risk factors in patients with type II diabetes. Diabetes Care. 1996; 19:64-6. [IDIS 362115] [PubMed 8720537]

54. Dornan T, Heller S, Peck G et al. Double-blind evaluation of efficacy and tolerability of metformin in NIDDM. Diabetes Care. 1991; 14:342-44. [PubMed 2060439]

55. Food and Drug Administration. Labeling for oral hypoglycemic drugs of the sulfonylurea class. [Docket 75N-0062] Fed Regist. 1984; 49:14303-31.

56. DeFronzo RA. Pharmacologic therapy for type 2 diabetes mellitus. Ann Intern Med. 1999; 131:281-303. [IDIS 430576] [PubMed 10454950]

57. Mooradian AD, Thurman JE. Drug therapy of postprandial hyperglycaemia. Drugs. 1999; 57:19-29. [PubMed 9951949]

58. Landgraf R. Approaches to the management of postprandial hyperglycaemia. Exp Clin Endocrinol Diabetes. 1999; 107(Suppl 4):S128-32.

59. Luna B, Hughes ATD, Feinglos MN. The use of insulin secretagogues in the treatment of type 2 diabetes. Prim Care. 1999; 26:895-15. [PubMed 10523467]

60. Balfour JA, Faulds D. Repaglinide. Drugs Aging. 1998; 13:173-80. [PubMed 9739505]

61. Guay DRP. Repaglinide, a novel, short-acting hypoglycemic agent for type 2 diabetes mellitus. Pharmacotherapy. 1998; 18:1195-1204. [IDIS 417628] [PubMed 9855316]

62. Anon. Repaglinide for type 2 diabetes mellitus. Med Lett Drugs Ther. 1998; 40:55-6. [PubMed 9618664]

63. Malaisse WJ. Repaglinide, a new oral antidiabetic agent: a review of recent preclinical studies. Eur J Clin Invest. 1999; 29(Suppl 2):21-9. [PubMed 10383607]

64. Owens DR. Repaglinide: a new short-acting insulinotropic agent for the treatment of type 2 diabetes. Eur J Clin Invest. 1999; 29(Suppl 2):30-7. [PubMed 10383608]

65. Gomis R. Repaglinide as monotherapy in type 2 diabetes. Exp Clin Endocrinol Diabetes. 1999; 107(Suppl 4):S133-5. [PubMed 10522838]

66. Schwartz SL, Goldberg RB, Strange P. Repaglinide in type 2 diabetes: a randomized, double blind, placebo-controlled, dose-response study. Repaglinide Study Group. Diabetes. 1998; 47(Suppl 1):A98.

67. Damsbo P, Marbury TC, Hatorp V et al. Flexible prandial glucose regulation with repaglinide in patients with type 2 diabetes. Diabetes Res Clin Pract. 1999; 45:31-9. [PubMed 10499883]

68. Damsbo P, Clauson P, Marbury TC et al. A double-blind randomized comparison of meal-related glycemic control by repaglinide and glyburide in well-controlled type 2 diabetic patients. Diabetes Care. 1999; 22:789-94. [IDIS 442501] [PubMed 10332683]

69. Expert Committee of the Canadian Diabetes Advisory Board. Clinical practice guidelines for treatment of diabetes mellitus. CMAJ. 1992; 147:697-712. [PubMed 1521215]

70. Chow CC, Tsang L, Sorensen J et al. Comparison of insulin with or without continuation of oral hypoglycemic agents in the treatment of secondary failure in NIDDM patients. Diabetes Care. 1995; 18:307-14. [IDIS 346283] [PubMed 7555472]

71. Novo Nordisk, Princeton, NJ: Personal communication.

72. Mooradian AD, Chehade J. Implications of the UK Prospective Diabetes Study. Drugs Aging. 2000; 16:159-64. [PubMed 10803856]

73. Shank WA Jr, Morrison AD. Oral sulfonylureas for the treatment of type II diabetes: an update. South Med J. 1986; 79:337-43. [IDIS 213870] [PubMed 3082015]

74. Zimmet P, Collier G. Clinical efficacy of metformin against insulin resistance parameters. Drugs. 1999; 58(Suppl 1):21-8. [PubMed 10576521]

75. United Kingdom Prospective Diabetes Study Group. United Kingdom prospective diabetes study (UKPDS) 13: relative efficacy of randomly allocated diet, sulphonylurea, insulin, or metformin in patients with newly diagnosed non-insulin dependent diabetes followed for three years. BMJ. 1995; 310:83-8. [IDIS 341678] [PubMed 7833731]

76. Koda-Kimble MA, Carlisle BA. Diabetes mellitus. In: Young LY, Koda-Kimble MA, eds. Applied therapeutics: the clinical use of drugs. 6th ed. Vancouver, WA: Applied Therapeutics, Inc; 1995: 48-1–48-62.

77. Ladriere L, Malaisse-Lagae F, Fuhlendorff J et al. Repaglinide, glibenclamide, and glimepiride administration to normal and hereditary diabetes rats. Eur J Pharmacol. 1997; 335:227-34. [PubMed 9369378]

78. Schwartz SL, Strange P, and the Repaglinide Study Group. Repaglinide does not accumulate in patients with type 2 diabetes. Diabetes. 1998; 47(Suppl 1):A357.

79. Ampudia-Blasco FJ, Heinemann L, Bender R et al. Comparative dose-related time-action profiles of glibenclamide and a new non-sulfonylurea drug, AG-EE 623 ZW, during euglycemic clamp in healthy subjects. Diabetologia. 1994; 37:703-7. [PubMed 7958542]

80. Jovanovic L, Dailey III G, Won-Chin H et al. Repaglinide in type 2 diabetes: a 24-week, fixed-dose efficacy and safety study. J Clin Pharmacol. 2000; 40:49-57. [IDIS 439087] [PubMed 10631622]

81. Goldberg RB, Damsbo P, Einhorn D et al. A randomized placebo-controlled trial of repaglinide in the treatment of type 2 diabetes. Diabetes Care. 1998; 21:1897-1903. [IDIS 416068] [PubMed 9802740]

82. Turner RC, Cull CA, Frighi V et al. Glycemic control with diet, sulfonlyurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirements for multiple therapies (UKPDS 49). JAMA. 1999; 281:2005-12. [IDIS 425712] [PubMed 10359389]

83. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998; 352:837-53. [IDIS 413216] [PubMed 9742976]

84. American Diabetes Association. Implications of the United Kingdom Prospective Diabetes Study. Diabetes Care. 2000;23 (Suppl 1).

85. Matthews DR, Cull CA, Stratton RR et al. UKPDS 26: sulphonylurea failure in non-insulin-dependent diabetic patients over 6 years. Diabet Med. 1998; 15:297-303. [PubMed 9585394]

86. Genuth P. United Kingdom prospective diabetes study results are in. J Fam Pract. 1998; 47:(Suppl 5):S27.

87. Bretzel RG, Voit K, Schatz H et al. The United Kingdom Prospective Diabetes Study (UKPDS): implications for the pharmacotherapy of type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes. 1998; 106:369-72. [PubMed 9831300]

88. Nathan DM. Some answers, more controversy, from UKDS. Lancet. 1998; 352:832-3. [IDIS 413214] [PubMed 9742972]

89. UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metfromin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998; 352:854-65. [IDIS 413217] [PubMed 9742977]

90. American Diabetes Association. The United Kingdom Prosepective Diabetes Study (UKPDS) for type 2 diabetes: what you need to know about the results of a long-term study. Washington, DC; September 15, 1998. From American Diabetes Association web site.

91. Davis TM. United Kingdom Prospective Diabetes Study: the end of the beginning? Med J Aust. 1998; 169:511-2.

92. Watkins PJ. UKPDS: a message of hope and a need for change. Diabet Med. 1998; 15:895-6. [PubMed 9827842]

93. Donahue RP, Abbott RD, Reed DM et al. Post challenge glucose concentration and coronary heart disease in men of Japanese ancestry. Honolulu Heart Program. Diabetes. 1987; 36:689-92. [PubMed 3569669]

94. Curb JD, Rodriguez BL, Burchfiel CM et al. Sudden death, impaired glucose tolerance, and diabetes in Japanese-American men. Circulation. 1995; 91:2591-5. [PubMed 7743621]

95. Fuller JH, Shipley MJ, Rose G et al. Coronary heart disease risk and impaired glucose tolerance: the Whitehall Study. Lancet. 1980; 1:1373-6. [PubMed 6104171]

96. Jackson CA, Yddkin JS, Forrest RD. A comparison of the relationships of the glucose tolerance test and the glycated hemoglobin assay with diabetic vascular disease in the community. The Islington Diabetes Survey. Diabetes Res Clin Pract. 1992; 17:111-23. [PubMed 1425145]

97. Jarrett RJ, McCArtney P, Keen H. The Bedford Survey: ten year mortality rates in newly diagnosed diabetics, borderline diabetics and normoglycemic controls and risk indices for coronary heart disease in borderline diabetics. Diabetologia. 1982; 22:79-84. [PubMed 7060853]

98. Lowe LP, Liu K, Greenland P et al. Diabetes, asymptomatic hyperglycaemia and 22-year mortality in black and white men. Diabetes Care. 1997; 20:163-9. [PubMed 9118765]

99. Wolffenbuttel BHR, Landgraf R, and the Dutch and German Repaglinide Study Group. A 1-year multicenter randomized double-blind comparison of repaglinide and glycuride for the treatment of type 2 diabetes. Diabetes Care. 1999; 22:463-7. [IDIS 440621] [PubMed 10097930]

100. Marbury T, Huang W-C, Strange P et al. Repaglinide versus glyburide: a one-year comparison trial. Diabetes Res Clin Pract. 1999; 43:155-66. [PubMed 10369424]

101. Hatorp V, Huang W-C, Strange P. Repaglinide pharmacokinetics in healthy young adult and elderly subjects. Clin Ther. 1999; 21:702-10. [IDIS 428165] [PubMed 10363735]

102. Moses R. Repaglinide in combination therapy with metformin in type 2 diabetes. Exp Clin Endocrinol Diabetes. 1999; 107(Supp 4):S136-S139. [PubMed 10522839]

103. Hatorp V, Huang W-C, Strange P. Pharmacokinetic profiles of repaglinide in elderly subjects with type 2 diabetes. J Clin Endocrinol Metab. 1999; 84:1475-8. [IDIS 427767] [PubMed 10199798]

104. Marbury TC, Ruckle JL, Hatorp V et al. Pharmacokinetics of repaglinide in subjects with renal impairment. Clin Pharmacol Ther. 2000; 67:7-15. [IDIS 442132] [PubMed 10668848]

105. Hatorp V, Walther KH, Christensen MS et al. Single-dose pharmacokinetics of repaglinide in subjects with chronic liver disease. J Clin Pharmacol. 2000; 40:142-52. [IDIS 441945] [PubMed 10664920]

106. Hatorp V, Thomsen MS. Drug interaction studies with repaglinide: repaglinide on digoxin or theophylline pharmacokinetics and cimetidine on repaglinide pharmacokinetics. J Clin Pharmacol. 2000; 40:184-92. [IDIS 441949] [PubMed 10664925]

107. van Heiningen PNM, Hatorp V, Nielsen KK et al. Absorption, metabolism and excretion of a single oral dose of14C-repaglinide during repaglinide multiple dosing. Eur J Clin Pharmacol. 1999; 55:521-5. [IDIS 436887] [PubMed 10501822]

108. Spiller HA. Management of antidiabetic medications in overdose. Drug Saf. 1998; 19:411-24. [PubMed 9825953]

109. American Diabetes Association. Type 2 diabetes in children and adolescents. Pediatrics. 2000; 105:671-80. [IDIS 443594] [PubMed 10699131]

110. American Diabetes Association. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 2000; 23(Suppl 1):S4-19.

111. Pi-Sunyer FX. Obesity. In: Goldman L, Bennett JC, eds. Cecil textbook of medicine. 21st ed. Philadelphia: WB Saunders Co; 2000.

112. Haffner SM, Hanefeld M, Fischer S et al. Glibenclamide, but not acarbose, increases leptin concentrations parallel to changes in insulin in subjects with NIDDM. Diabetes Care. 1997; 20:1430-4. [IDIS 393377] [PubMed 9283792]

113. Strange P, Schwartz SL, Graf RJ et al. Pharmacokinetics, pharmacodynamics, an dose-response relationship of repaglinide in type 2 diabetes. Diabetes Tech Ther. 1999; 1:247-56.

114. Dejgaard A, Madsbad S, Kilhovd B et al. Repaglinide compared to glipizide in the treatment of type 2 diabetic patients. Diabetologia. 1998; 41(Suppl 1):A236.

115. Landin-Ollsson M, Brogard JMM, Eriksson J et al. The efficacy of repaglinide in combination with bedtime NPH-Insulin in patients with type 2 diabetes. Diabetes. 1999; 48(Suppl 1):A117. [PubMed 10426375]

116. Chan JCN, Cockram CS. Drug-induced disturbances of carbohydrate metabolism. Adv Drug React Tox Rev. 1991; 10:1-29.

117. Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus. JAMA. 2002; 287:2563-9. [IDIS 480500] [PubMed 12020338]

118. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993; 329:977-86. [IDIS 320201] [PubMed 8366922]

119. Bayer Corporation. Precose (acarbose) tablets prescribing information. West Haven, CT; 2003 Mar.

Hide
(web2)