GlyBURIDE

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Medication Safety Issues

Sound-alike/look-alike issues:

GlyBURIDE may be confused with glipiZIDE, Glucotrol®

Dia?eta® may be confused with Diabinese®, Zebeta®

Micronase® may be confused with microK®, miconazole, Micronor®, Microzide™

High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.

Pronunciation

(GLYE byoor ide)

U.S. Brand Names

* Dia?eta®
* Glynase® PresTab®
* Micronase®

Index Terms

* Diabeta
* Glibenclamide
* Glybenclamide
* Glybenzcyclamide

Generic Available

Yes

Canadian Brand Names

* Albert® Glyburide
* Apo-Glyburide®
* Dia?eta®
* Euglucon®
* Gen-Glybe
* Novo-Glyburide
* Nu-Glyburide
* PMS-Glyburide
* ratio-Glyburide
* Sandoz-Glyburide

Pharmacologic Category

*
Antidiabetic Agent, Sulfonylurea

Pharmacologic Category Synonyms

* Oral Hypoglycemic Agent, Sulfonylurea
* Sulfonylurea

Use

Management of type 2 diabetes mellitus (noninsulin dependent, NIDDM)

Use: Unlabeled/Investigational

Alternative to insulin in women for the treatment of gestational diabetes (11-33 weeks gestation)

Pregnancy Risk Factor

B/C (manufacturer dependent)

Pregnancy Implications

Glyburide was not found to significantly cross the placenta in vitro and was not found in the cord serum infants of mothers taking glyburide for gestational diabetes mellitus (GDM). Reported teratogenic effects may be due to poorly controlled maternal diabetes; abnormal blood glucose levels in the mother are associated with a higher incidence of congenital abnormalities. Nonteratogenic effects such as hypoglycemia in the neonate have been associated with maternal glyburide use. The manufacturer recommends that if glyburide is used during pregnancy, it should be discontinued at least 2 weeks before the expected delivery date. Although studies have shown positive outcomes using glyburide for the treatment of GDM, use may not be appropriate for all women. When compared to insulin for the treatment of GDM, as the severity of GDM increased, the success rate of treatment decreased. It should be noted that studies using glyburide for the treatment of GDM have initiated treatment after the period of organogenesis. Insulin is considered the drug of choice for the control of diabetes mellitus during pregnancy.Reproduction studies differ by manufacturer labeling. Because adverse events were not observed in animal reproduction studies, one manufacturer classifies glyburide as pregnancy category B. Because adverse events were noted in animal studies during the period of lactation, another manufacturer classifies glyburide as pregnancy category C.

Lactation

Does not enter breast milk/ use caution

Breast-Feeding Considerations

Data from initial studies note that glyburide was not detected in breast milk. Breast-feeding is not recommended by the manufacturer. Potentially, hypoglycemia may occur in a nursing infant exposed to a sulfonylurea via breast milk.

Contraindications

Hypersensitivity to glyburide, any component of the formulation, or other sulfonamides; type 1 diabetes mellitus (insulin dependent, IDDM), diabetic ketoacidosis; concurrent use with bosentan

Warnings/Precautions

Concerns related to adverse reactions:

• Cardiovascular mortality: Product labeling states oral hypoglycemic drugs may be associated with an increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin. Data to support this association are limited, and several studies, including a large prospective trial (UKPDS) have not supported an association.

• Hypoglycemia: All sulfonylurea drugs are capable of producing severe hypoglycemia. Hypoglycemia is more likely to occur when caloric intake is deficient, after severe or prolonged exercise, when ethanol is ingested, or when more than one glucose-lowering drug is used. It is also more likely in elderly patients, malnourished patients and in patients with impaired renal, hepatic, adrenal and/or pituitary function; use with caution.

• Sulfonamide allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonamide allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe.

Disease-related concerns:

• Stress-related states: It may be necessary to discontinue therapy and administer insulin if the patient is exposed to stress (fever, trauma, infection, surgery).

Special populations:

• Elderly: Rapid and prolonged hypoglycemia (>12 hours) despite hypertonic glucose injections have been reported; age and hepatic and renal impairment are independent risk factors for hypoglycemia; dosage titration should be made at weekly intervals.

• Pediatrics: Safety and efficacy have not been established in children.

Adverse Reactions

Frequency not defined.

Cardiovascular: Vasculitis

Central nervous system: Headache, dizziness

Dermatologic: Erythema, maculopapular eruptions, morbilliform eruptions, pruritus, purpura, rash, urticaria, photosensitivity reaction

Endocrine & metabolic: Disulfiram-like reaction, hypoglycemia, hyponatremia (SIADH reported with other sulfonylureas)

Gastrointestinal: Nausea, epigastric fullness, heartburn, constipation, diarrhea, anorexia

Genitourinary: Nocturia

Hematologic: Leukopenia, thrombocytopenia, hemolytic anemia, agranulocytosis, aplastic anemia, pancytopenia, porphyria cutanea tarda

Hepatic: Cholestatic jaundice, hepatitis, transaminase increased

Neuromuscular & skeletal: Arthralgia, myalgia, paresthesia

Ocular: Blurred vision

Renal: Diuretic effect (minor)

Miscellaneous: Allergic reaction

Drug Interactions

Inhibits CYP2C8 (weak), 3A4 (weak)

Beta-blockers: Beta-blockers may enhance the hypoglycemic effect of glyburide and mask tachycardia as an initial symptom of hypoglycemia.

Bosentan: Glyburide may enhance the hepatotoxic effect and increase the metabolism of bosentan. Bosentan may increase the metabolism of glyburide. Concomitant use is contraindicated

Chloramphenicol: Chloramphenicol may decrease the metabolism of glyburide.

Cimetidine: Cimetidine may decrease the metabolism, via CYP isoenzymes, of glyburide.

Cyclic antidepressants: Cyclic antidepressants may enhance the hypoglycemic effect of glyburide.

Cyclosporine: Glyburide may increase the serum concentration of cyclosporine.

Fibric acid derivatives: Fibric acid derivatives may enhance the hypoglycemic effect of glyburide.

Fluconazole: Fluconazole may increase the serum concentration of glyburide.

Pegvisomant: Pegvisomant may enhance the hypoglycemic effect of glyburide.

Quinolone antibiotics: Quinolone antibiotics may enhance the hypoglycemic effect of glyburide.

Rifampin: Rifampin may increase the metabolism, via CYP isoenzymes, of glyburide.

Salicylates: Salicylates may enhance the hypoglycemic effect of glyburide. Of concern with regular, higher doses of salicylates, not sporadic, low doses.

Sulfonamide derivatives (sulfadiazine, sulfadoxine, sulfamethoxazole, sulfisoxazole): Sulfonamide derivatives (except sulfacetamide) may enhance the hypoglycemic effect of glyburide.

Ethanol/Nutrition/Herb Interactions

Ethanol: Caution with ethanol (may cause hypoglycemia).

Herb/Nutraceutical: Herbs with hypoglycemic properties may enhance the hypoglycemic effect of glyburide. This includes alfalfa, aloe, bilberry, bitter melon, burdock, celery, damiana, fenugreek, garcinia, garlic, ginger, ginseng (American), gymnema, marshmallow, stinging nettle

Mechanism of Action

Stimulates insulin release from the pancreatic beta cells; reduces glucose output from the liver; insulin sensitivity is increased at peripheral target sites

Pharmacodynamics/Kinetics

Onset of action: Serum insulin levels begin to increase 15-60 minutes after a single dose

Duration: ?24 hours

Absorption: Significant within 1 hour

Distribution: 9-10 L

Protein binding, plasma: >99% primarily to albumin

Metabolism: Hepatic; forms metabolites (weakly active)

Half-life elimination: Diabeta®, Micronase®: 10 hours; Glynase® PresTab®: ?4 hours; may be prolonged with renal or hepatic impairment

Time to peak, serum: Adults: 2-4 hours

Excretion: Feces (50%) and urine (50%) as metabolites

Dosage

Oral: Adults:

Dia?eta®, Micronase®:

Initial: 2.5-5 mg/day, administered with breakfast or the first main meal of the day. In patients who are more sensitive to hypoglycemic drugs, start at 1.25 mg/day.

Increase in increments of no more than 2.5 mg/day at weekly intervals based on the patient's blood glucose response

Maintenance: 1.25-20 mg/day given as single or divided doses; maximum: 20 mg/day

Elderly: Initial: 1.25-2.5 mg/day, increase by 1.25-2.5 mg/day every 1-3 weeks

Micronized tablets (Glynase® PresTab®): Adults:

Initial: 1.5-3 mg/day, administered with breakfast or the first main meal of the day in patients who are more sensitive to hypoglycemic drugs, start at 0.75 mg/day. Increase in increments of no more than 1.5 mg/day in weekly intervals based on the patient's blood glucose response.

Maintenance: 0.75-12 mg/day given as a single dose or in divided doses. Some patients (especially those receiving >6 mg/day) may have a more satisfactory response with twice-daily dosing. Maximum: 12 mg/day

Dosing adjustment/comments in renal impairment: Clcr <50 mL/minute: Not recommended

Dosing adjustment in hepatic impairment: Use conservative initial and maintenance doses and avoid use in severe disease

Administration: Oral

Administer with meals at the same time each day. Patients who are anorexic or NPO may need to have their dose held to avoid hypoglycemia.

Monitoring Parameters

Signs and symptoms of hypoglycemia, fasting blood glucose, hemoglobin A1c

Reference Range

Recommendations for glycemic control in adults with diabetes:

Hb A1c: <7%

Preprandial capillary plasma glucose: 70-130 mg/dL

Peak postprandial capillary blood glucose: <180 mg/dL

Blood pressure: <130/80 mm Hg

Dietary Considerations

Should be taken with meals at the same time each day. Dietary modification based on ADA recommendations is a part of therapy. Decreases blood glucose concentration. Hypoglycemia may occur. Must be able to recognize symptoms of hypoglycemia (palpitations, sweaty palms, lightheadedness).

Patient Education

Do not take any new medication during therapy unless approved by prescriber. This medication is used to control diabetes; it is not a cure. Monitor glucose as recommended by prescriber. Other important components of treatment plan may include prescribed diet and exercise regimen (consult prescriber or diabetic educator). If you experience hypoglycemic reaction, contact prescriber immediately. Always carry quick source of sugar with you. Take exactly as directed, 30 minutes before meal(s) at the same time each day. Do not change dose or discontinue without consulting prescriber. Avoid alcohol while taking this medication; could cause severe reaction. Do not take other medication within 2 hours of this medication unless advised by prescriber. You may experience more sensitivity to sunlight (use sunscreen, wear protective clothing and eyewear, and avoid direct sunlight); headache; or nausea (consult prescriber if these persist). Report severe or persistent side effects; hypoglycemia (palpitations, sweaty palms, lightheadedness); extended vomiting, diarrhea, or constipation; flu-like symptoms; skin rash; easy bruising or bleeding; or change in color of urine or stool. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Do not breast-feed.

Geriatric Considerations

Rapid and prolonged hypoglycemia (>12 hours) despite hypertonic glucose injections has been reported; age, hepatic, and renal impairment are independent risk factors for hypoglycemia; dosage titration should be made at weekly intervals. How “tightly” a geriatric patient's blood glucose should be controlled is controversial; however, a fasting blood sugar <150 mg/dL is now an acceptable endpoint. Such a decision should be based on the patient's functional and cognitive status, how well they recognize hypoglycemic or hyperglycemic symptoms, and how to respond to them and their other disease states. Use with caution in the elderly with renal insufficiency.

Anesthesia and Critical Care Concerns/Other Considerations

The possibility of higher doses of sulfonylureas eliciting an increase in cardiovascular events, because of their effects on blocking potassium sensitive ATP channels, has been raised. Longer-term prospective trials of sulfonylurea therapy, such as the UKPDS, do not reveal any increased cardiovascular mortality.

Cardiovascular Considerations

The possibility of higher doses of sulfonylureas eliciting an increase in cardiovascular events, because of their effects on blocking potassium sensitive ATP channels, has been raised. However, there are presently only limited data to support this premise, particularly with newer generation agents. An early study suggested poor cardiovascular outcomes in patients with diabetes treated with tolbutamide. Retrospective studies evaluating cardiovascular outcomes following angioplasty and acute myocardial infarction in patients with diabetes receiving newer sulfonylureas are inconsistent. Longer-term prospective trials of sulfonylurea therapy, such as the UKPDS, do not reveal any increased cardiovascular mortality.

Dental Health: Effects on Dental Treatment

Glyburide-dependent patients with diabetes (noninsulin dependent, type 2) should be appointed for dental treatment in morning in order to minimize chance of stress-induced hypoglycemia.

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

Dizziness is common

Mental Health: Effects on Psychiatric Treatment

May rarely cause agranulocytosis; use caution with clozapine and carbamazepine; phenothiazines and TCAs may antagonize glimepiride hypoglycemic effects; MAO inhibitors and TCAs may enhance hypoglycemic effects

Nursing: Physical Assessment/Monitoring

Assess allergy history prior to beginning therapy. Assess potential for interactions with other prescriptions, OTC medications, or herbal products patient may be taking. Assess results of laboratory tests, therapeutic effectiveness, and adverse response (eg, hypoglycemia) at regular intervals during therapy. Teach patient proper use (or refer patient to diabetic educator) for instruction, possible side effects/appropriate interventions, and adverse symptoms to report.

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet: 1.25 mg, 2.5 mg, 5 mg

Dia?eta®, Micronase®: 1.25 mg, 2.5 mg, 5 mg

Tablet, micronized: 1.5 mg, 3 mg, 6 mg

Glynase® PresTab®: 3 mg, 6 mg

Pricing: U.S. (www.drugstore.com)

Tablets (Diabeta)

1.25 mg (50): $27.11

2.5 mg (30): $28.20

5 mg (30): $35.99

Tablets (GlyBURIDE)

1.25 mg (30): $12.99

2.5 mg (30): $12.99

5 mg (30): $11.99

Tablets (GlyBURIDE Micronized)

1.5 mg (60): $16.00

3 mg (60): $20.99

6 mg (60): $33.99

Tablets (Glynase)

1.5 mg (60): $47.69

3 mg (60): $70.13

6 mg (60): $109.42

Tablets (Micronase)

1.25 mg (30): $17.39

2.5 mg (30): $28.10

5 mg (30): $44.99

References

ACOG Practice Bulletin, Clinical Management Guidelines for Obstetrician-Gynecologists, Number 60, March 2005, "Pregestational Diabetes Mellitus," Obstet Gynecol , 2005, 105(3):675-85.

American Diabetes Association, “Standards of Medical Care in Diabetes Mellitus - 2008,” Diabetes Care, 2008, 30(Suppl 1):12-54.

“A Study of the Effects of Hypoglycemia Agents on Vascular Complications in Patients With Adult-onset Diabetes. VI. Supplementary Report on Nonfatal Events in Patients Treated With Tolbutamide. The University Group Diabetes Program,” Diabetes, 1976, 25(12):1129-53.

Brodows RG, “Benefits and Risks With Glyburide and Glipizide in Elderly NIDDM Patients,” Diabetes Care, 1992, 15(1):75-80.

“Effect of Intensive Blood-Glucose Control With Metformin on Complications in Overweight Patients With Type 2 Diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group,” Lancet, 1998, 352(9131):854-65.

Elliott BD, Schenker S, Langer O, et al, "Comparative Placental Transport of Oral Hypoglycemic Agents in Humans: A Model of Human Placental Drug Transfer," Am J Obstet Gynecol, 1994, 171(3):653-60.

Feig DS, Briggs GG, Kraemer JM, et al, "Transfer of Glyburide and Glipizide Into Breast Milk," Diabetes Care, 2005, 28(8):1851-5.

Gabbe SG and Graves CR, "Management of Diabetes Mellitus Complicating Pregnancy," Obstet Gynecol, 2003, 102(4):857-68.

Garratt KN, Brady PA, Hassinger NL, et al, “Sulfonylurea Drugs Increase Early Mortality in Patients With Diabetes Mellitus After Direct Angioplasty for Acute Myocardial Infarction,” J Am Coll Cardiol, 1999, 33(1):119-24.

Gavin JR 3d, “Glyburide: New Insights Into Its Effects on the Beta Cell and Beyond - Introduction,” Am J Med, 1990, 89(2A):1S-2S.

“Intensive Blood-Glucose Control With Sulphonylureas or Insulin Compared With Conventional Treatment and Risk of Complications in Patients With Type 2 Diabetes (UKPDS 33) UK Prospective Diabetes Study (UKPDS) Group,” Lancet, 1998, 352(9131):837-53.

Jacobson GF, Ramos GA, Ching JY, et al, "Comparison of Glyburide and Insulin for the Management of Gestational Diabetes in a Large Managed Care Organization," Am J Obstet Gynecol, 2005, 193(1):118-24.

Klamann A, Sarfert P, Launhardt V, et al, “Myocardial Infarction in Diabetic vs Nondiabetic Subjects. Survival and Infarct Size Following Therapy With Sulfonylureas (Glibenclamide),” Eur Heart J, 2000, 21(3):220-9.

Langer O, Conway D, Berkus M, et al, “A Comparison of Glyburide and Insulin in Women With Gestational Diabetes Mellitus,” N Engl J Med, 2000, 343(16):1134-8.

Langer O, Yogev Y, Xenakis EM, et al, "Insulin and Glyburide Therapy: Dosage, Severity Level of Gestational Diabetes, and Pregnancy Outcome," Am J Obstet Gynecol , 2005, 192(1):134-9.

Meinert CL, Knatterud GL, Prout TE, et al, “A Study of the Effects of Hypoglycemic Agents on Vascular Complications in Patients With Adult-Onset Diabetes. II. Mortality Results,” Diabetes, 1970, 19:789-830.

Nadel HL, “Formulary Conversion From Glipizide to Glyburide: A Cost-Minimization Analysis,” Hosp Pharm, 1995, 30:472-74.

Nataas OB and Nesthus I, “Immune Haemolytic Anaemia Induced by Glibenclamide in Selective IgA Deficiency,” Br Med J (Clin Res Ed), 1987, 295(6594):366-7.

O'Keefe JH, Blackstone EH, Sergeant P, et al, “The Optimal Mode of Coronary Revascularization for Diabetics. A Risk-Adjusted Long-Term Study Comparing Coronary Angioplasty and Coronary Bypass Surgery,” Eur Heart J, 1998, 19(11):1696-703.

Pearson JG, “Pharmacokinetics of Glyburide,” Am J Med, 1985, 79(3B):67-71.

Rosenstock J, Corrao PJ, Goldberg RB, et al, “Diabetes Control in the Elderly: A Randomized, Comparative Study of Glyburide Versus Glipizide in Noninsulin-Dependent Diabetes Mellitus,” Clin Ther, 1993, 15(6):1031-40.

Schwinghammer TL, Antal EJ, Kubacka RT, et al, “Pharmacokinetics and Pharmacodynamics of Glyburide in Young and Elderly Nondiabetic Adults,” Clin Pharm, 1991, 10(7):532-8.

Sillence DO and Court JM, “Glibenclamide-Induced Hypoglycemia,” Br Med J, 1975, 3(5981):490-1.

Sonnenblick M and Shilo S, “Glibenclamide Induced Prolonged Hypoglycaemia,” Age Ageing, 1986, 15(3):185-9.

International Brand Names

* Amecladin (PH)
* Apo-Glibenclamide (NZ)
* Benclamin (TH)
* Betanase (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE)
* Betanese 5 (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW)
* Bevoren (LU)
* Calabren (CZ)
* Clamide (HK)
* Daonil (AE, AR, AU, BB, BD, BE, BF, BH, BJ, BM, BO, BR, BS, BZ, CH, CI, CL, CN, CO, CR, CY, DK, DO, EC, EG, ET, FR, GB, GH, GM, GN, GR, GT, GY, HK, HN, HR, ID, IE, IL, IN, IQ, IR, IT, JM, JO, JP, KE, KP, KW, LB, LR, LU, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NI, NL, NO, NZ, OM, PA, PE, PH, PK, PR, PT, PY, QA, RU, SA, SC, SD, SG, SL, SN, SR, SV, SY, TH, TN, TT, TW, TZ, UG, UY, VE, YE, ZA, ZM, ZW)
* Daono (TH)
* Debtan (TH)
* Diaben (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE)
* Diabitor (PH)
* Dibelet (MY, TH)
* Euclamin (PL)
* Euglucan (FR)
* Euglucon (AE, AR, AT, AU, BB, BD, BE, BF, BH, BJ, BM, BO, BR, BS, BZ, CH, CI, CL, CN, CO, CR, CY, CZ, DE, DO, EC, EG, ES, ET, FI, GH, GM, GN, GR, GT, GY, HK, HN, HR, ID, IL, IN, IQ, IR, IT, JM, JO, JP, KE, KP, KW, LB, LR, LU, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NI, NL, OM, PA, PE, PH, PK, PR, PT, PY, QA, RU, SA, SC, SD, SE, SG, SL, SN, SR, SV, SY, TH, TN, TT, TW, TZ, UG, UY, VE, YE, ZA, ZM, ZW)
* Euglusid (CN)
* Gilemal (AT, BG, HN, HU)
* Gliban (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE)
* Glibedal (HR)
* Gliben (IT, NZ)
* Glibenclamid (HR)
* Glibenclamid Pharmavit (HU)
* Glibenclamid-ratiopharm (LU)
* Glibenhexal (LU)
* Glibens (CO)
* Glibesyn (MY, SG)
* Glibet (IN)
* Glibetic (IL)
* Glibil (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE)
* Gliboral (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW)
* Glidiabet (PE)
* Glimel (AU, HK, SG)
* Glimide (MY)
* Glisulin (KP)
* Glitisol (BB, BM, BS, BZ, GY, HK, JM, NL, SR, TT)
* Gluben (IL)
* Glucal (MX)
* Glucobene (HU)
* Glucomid (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW)
* Gluconic (ID)
* Glulo (ID)
* Glyamid (ID)
* Glycomin (ZA)
* Glynase (BB, BM, BS, BZ, GY, JM, NL, SR, TT)
* Hemi-Daonil (AR, FR, MA, NL)
* Insol (PH)
* Lodulce (PH)
* Maninil (EE, PL)
* Manoglucon (TH)
* Melix (AE, BB, BF, BH, BJ, BM, BS, BZ, CI, CY, EG, ET, GH, GM, GN, GY, IL, IQ, IR, JM, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, NL, OM, QA, SA, SC, SD, SL, SN, SR, SY, TN, TT, TZ, UG, YE, ZA, ZM, ZW)
* Miglucan (FR)
* Norboral (MX)
* Norglicem (ES)
* Orabetic (PH)
* Pira (AR)
* Renabetic (ID)
* Semi-Daonil (AE, AR, AU, BH, CH, CY, EG, GB, HK, ID, IE, IL, IQ, IR, JO, KW, LB, LY, MA, NZ, OM, PT, QA, SA, SY, YE)
* Semi-Euglucon (AR, AT, AU, NL, PH, TH)
* Sugril (TH)
* Tiabet (ID)
* Trodeb (ID)
* Unil-5 (TH)
* Xeltic (HK)