Glibenclamide

Glibenclamide
Clinical data
Trade namesDiabeta, Glynase, Micronase, others
Other namesGlyburide (USAN US)
AHFS/Drugs.comMonograph
MedlinePlusa684058
License data
Pregnancy
category
  • AU: C
Routes of
administration		By mouth
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
  • US: ℞-only
  • EU: Rx-only
Pharmacokinetic data
Protein bindingExtensive
MetabolismLiver hydroxylation (CYP2C9-mediated)
Elimination half-life10 hours
ExcretionKidney and bile duct
Identifiers
  • 5-chloro-N-[2-[4-(cyclohexylcarbamoylsulfamoyl)
    phenyl]ethyl]-2-methoxybenzamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.030.505 Edit this at Wikidata
Chemical and physical data
FormulaC23H28ClN3O5S
Molar mass494.00 g·mol−1
3D model (JSmol)
Melting point169 to 170 °C (336 to 338 °F)
  • O=C(NC1CCCCC1)NS(=O)(=O)c2ccc(cc2)CCNC(=O)c3cc(Cl)ccc3OC
  • InChI=1S/C23H28ClN3O5S/c1-32-21-12-9-17(24)15-20(21)22(28)25-14-13-16-7-10-19(11-8-16)33(30,31)27-23(29)26-18-5-3-2-4-6-18/h7-12,15,18H,2-6,13-14H2,1H3,(H,25,28)(H2,26,27,29) checkY
  • Key:ZNNLBTZKUZBEKO-UHFFFAOYSA-N checkY
  (verify)

Glibenclamide, also known as glyburide (U.S. English), is an antidiabetic medication used to treat type 2 diabetes. It is recommended that it be taken together with diet and exercise. It may be used with other antidiabetic medication. It is not recommended for use by itself in type 1 diabetes. It is taken by mouth.

Common side effects include nausea and heartburn. Serious side effects may include angioedema and low blood sugar. It is generally not recommended during pregnancy but can be used during breastfeeding. It is in the sulfonylureas class of medications and works by increasing the release of insulin from the pancreas.

Glibenclamide was discovered in 1969 and approved for medical use in the United States in 1984. It is available as a generic medication. In 2021, it was the 214th most commonly prescribed medication in the United States, with more than 2 million prescriptions.

Medical uses

Glibenclamide is used to lower the blood sugar level in patients with type 2 diabetes mellitus, which is not controlled by diet and exercise alone.

It is not as good as either metformin or insulin in those who have gestational diabetes.


Side effects

Frequently reported side effects include: nausea, heartburn, weight gain, and bloating. The medication is also a major cause of medication-induced hypoglycemia. The risk is greater than with other sulfonylureas.

Contraindications

Glibenclamide may be not recommended in those with G6PD deficiency, as it may cause acute hemolysis.

Pregnancy and breastfeeding

It is generally not recommended during pregnancy but can be used during breastfeeding.

Mechanism of action

The medication, a sulfonylurea, works by binding to and inhibiting the ATP-sensitive potassium channels (KATP) inhibitory regulatory subunit sulfonylurea receptor 1 (SUR1) in pancreatic beta cells. This inhibition causes cell membrane depolarization, opening voltage-dependent calcium Channels.

This results in an increase in intracellular calcium in the pancreatic beta cell and subsequent stimulation of insulin release.

After a stroke, the blood–brain barrier is broken and glibenclamide can reach the central nervous system. Glibenclamide has been shown to bind more efficiently to the ischemic hemisphere. Moreover, under ischemic conditions SUR1, the regulatory subunit of the KATP- and the NCCa-ATP-channels, is expressed in neurons, astrocytes, oligodendrocytes, endothelial cells and by reactive microglia.

According to the research, this and other sulphonylurea drugs also have extra hepatic effects. It works by inhibiting the enzyme Carnityl Acyl Transferase I (CAT-I) indirectly, which is present in the mitochondria. This prevents the transport of long chain fatty acids into the mitochondria for beta-oxidation. This prevents hyperglycemia for which it is prescribed.

History

It was developed in 1966 in a cooperative study between Boehringer Mannheim (now part of Roche) and Hoechst (now part of Sanofi-Aventis).

Society and culture

Brand names

Glibenclamide is available as a generic medication, is manufactured by many pharmaceutical companies and is sold under many brand names including Gliben-J, Daonil, Diabeta, Euglucon, Gilemal, Glidanil, Glybovin, Glynase, Maninil, Micronase and Semi-Daonil. It is also available in a fixed-dose combination drug with metformin that is sold under various trade names, e.g. Bagomet Plus, Benimet, Glibomet, Gluconorm, Glucored, Glucovance, Metglib and many others.

References

  1. 1 2 3 4 5 6 7 8 9 10 "Glyburide Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Archived from the original on 31 March 2019. Retrieved 18 March 2019.
  2. ↑ "Glynase- glyburide tablet". DailyMed. 7 October 2017. Archived from the original on 6 October 2022. Retrieved 30 April 2022.
  3. 1 2 3 British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 692. ISBN 9780857113382.
  4. ↑ Diabetes in Clinical Practice: Questions and Answers from Case Studies. John Wiley & Sons. 2007. p. 342. ISBN 9780470059135.
  5. ↑ "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
  6. ↑ "Glyburide - Drug Usage Statistics". ClinCalc. Archived from the original on 12 April 2020. Retrieved 14 January 2024.
  7. ↑ Balsells M, García-Patterson A, Solà I, Roqué M, Gich I, Corcoy R (January 2015). "Glibenclamide, metformin, and insulin for the treatment of gestational diabetes: a systematic review and meta-analysis". BMJ. 350: h102. doi:10.1136/bmj.h102. PMC 4301599. PMID 25609400.
  8. ↑ "Glyburide: MedlinePlus Drug Information". MedlinePlus. Archived from the original on 14 April 2019. Retrieved 29 October 2019.
  9. ↑ Gangji AS, Cukierman T, Gerstein HC, Goldsmith CH, Clase CM (February 2007). "A systematic review and meta-analysis of hypoglycemia and cardiovascular events: a comparison of glyburide with other secretagogues and with insulin". Diabetes Care. 30 (2): 389–394. doi:10.2337/dc06-1789. PMID 17259518.
  10. ↑ Meloni G, Meloni T (January 1996). "Glyburide-induced acute haemolysis in a G6PD-deficient patient with NIDDM". British Journal of Haematology. 92 (1): 159–160. doi:10.1046/j.1365-2141.1996.275810.x. PMID 8562390. S2CID 41227257.
  11. ↑ Serrano-Martín X, Payares G, Mendoza-León A (December 2006). "Glibenclamide, a blocker of K+(ATP) channels, shows antileishmanial activity in experimental murine cutaneous leishmaniasis". Antimicrobial Agents and Chemotherapy. 50 (12): 4214–4216. doi:10.1128/AAC.00617-06. PMC 1693980. PMID 17015627.
  12. ↑ He Y, Chang Y, Peng Y, Zhu J, Liu K, Chen J, et al. (October 2022). "Glibenclamide Directly Prevents Neuroinflammation by Targeting SUR1-TRPM4-Mediated NLRP3 Inflammasome Activation In Microglia". Molecular Neurobiology. 59 (10): 6590–6607. doi:10.1007/s12035-022-02998-x. PMID 35972671. S2CID 242029244.
  13. ↑ "Glyburide". Lexicomp. Wolters Kluwer N.V. Archived from the original on 2 June 2023. Retrieved 3 June 2023.
  14. 1 2 Ortega FJ, Gimeno-Bayon J, Espinosa-Parrilla JF, Carrasco JL, Batlle M, Pugliese M, et al. (May 2012). "ATP-dependent potassium channel blockade strengthens microglial neuroprotection after hypoxia-ischemia in rats". Experimental Neurology. 235 (1): 282–296. doi:10.1016/j.expneurol.2012.02.010. hdl:2445/34278. PMID 22387180. S2CID 4828181.
  15. ↑ Simard JM, Woo SK, Schwartzbauer GT, Gerzanich V (September 2012). "Sulfonylurea receptor 1 in central nervous system injury: a focused review". Journal of Cerebral Blood Flow and Metabolism. 32 (9): 1699–1717. doi:10.1038/jcbfm.2012.91. PMC 3434627. PMID 22714048.
  16. ↑ Chen S, Ogawa A, Ohneda M, Unger RH, Foster DW, McGarry JD (July 1994). "More direct evidence for a malonyl-CoA-carnitine palmitoyltransferase I interaction as a key event in pancreatic beta-cell signaling". Diabetes. 43 (7): 878–883. doi:10.2337/diab.43.7.878. PMID 8013751. S2CID 25251669.
  17. ↑ Lehtihet M, Welsh N, Berggren PO, Cook GA, Sjoholm A (August 2003). "Glibenclamide inhibits islet carnitine palmitoyltransferase 1 activity, leading to PKC-dependent insulin exocytosis". American Journal of Physiology. Endocrinology and Metabolism. 285 (2): E438–E446. doi:10.1152/ajpendo.00057.2003. PMID 12684219. S2CID 175394.
  18. ↑ Marble A (1971). "Glibenclamide, a new sulphonylurea: whither oral hypoglycaemic agents?". Drugs. 1 (2): 109–115. doi:10.2165/00003495-197101020-00001. PMID 4999930. S2CID 13181386.
  19. ↑ "Daonil". News-Medical.net. Archived from the original on 26 June 2023. Retrieved 26 June 2023.
  20. ↑ "DiaBeta (Glyburide Tablets): Uses, Dosage, Side Effects, Interactions, Warning". RxList. Archived from the original on 26 June 2023. Retrieved 26 June 2023.
  21. ↑ "Glyburide and metformin". Lexicomp. Wolters Kluwer N.V. Archived from the original on 2 June 2023. Retrieved 3 June 2023.