Remogliflozin etabonate

Remogliflozin etabonate
Clinical data
Routes of
administration		By mouth
ATC code
  • none
Legal status
Legal status
  • Investigational
Pharmacokinetic data
MetabolismRemoglifozin is metabolized primarily by cytochrome P450 (CYP) 3A4 and to a lesser extent by CYP2C19 to GSK 279782 (the active metabolite) and GSK 333081 before being glucuronidated to generate inactive glucuronide conjugates.[1]
Identifiers
  • 5-Methyl-4-[4-(1-methylethoxy)benzyl]-1-(1-methylethyl)-1H-pyrazol-3-yl 6-O-(ethoxycarbonyl)-β-D-glucopyranoside
CAS Number
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC26H38N2O9
Molar mass522.595 g·mol−1
3D model (JSmol)
  • OC1C(COC(=O)OCC)OC(C(O)C1O)Oc(nn(C(C)C)c2C)c2Cc3ccc(cc3)OC(C)C
  • InChI=1S/C26H38N2O9/c1-7-33-26(32)34-13-20-21(29)22(30)23(31)25(36-20)37-24-19(16(6)28(27-24)14(2)3)12-17-8-10-18(11-9-17)35-15(4)5/h8-11,14-15,20-23,25,29-31H,7,12-13H2,1-6H3/t20-,21-,22+,23-,25+/m1/s1 ☒N
  • Key:UAOCLDQAQNNEAX-ABMICEGHSA-N ☒N
 ☒NcheckY (what is this?)  (verify)

Remogliflozin etabonate (INN/USAN)[2] is a drug of the gliflozin class for the treatment of non-alcoholic steatohepatitis ("NASH") and type 2 diabetes. Remogliflozin was discovered by the Japanese company Kissei Pharmaceutical and is currently being developed by BHV Pharma, a wholly owned subsidiary of North Carolina, US-based Avolynt, and Glenmark Pharmaceuticals through a collaboration with BHV.[3] In 2002, GlaxoSmithKline (GSK) received a license to use it. From 2002 to 2009, GSK carried out a significant clinical development program for the treatment of type-2 diabetes mellitus in various nations across the world and obesity in the UK. Remogliflozin etabonate's pharmacokinetics, pharmacodynamics, and clinical dose regimens were characterized in 18 Phase I and 2 Phase II investigations. Due to financial concerns, GSK stopped working on remogliflozin and sergliflozin, two further SGLT2 inhibitors that were licensed to the company, in 2009.[4] Remogliflozin was commercially launched first in India by Glenmark in May 2019.

Clinical trials

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Remogliflozin etabonate was shown to enhance urinary glucose excretion in rodents and humans. Early studies in diabetics improved plasma glucose levels.[5][6] Remogliflozin etabonate has been studied at doses up to 1000 mg.[7] A pair of 12-week phase 2b randomized clinical trials of diabetics published in 2015, found reductions in glycated hemoglobin and that it was generally well tolerated.[8] In a meta-analysis published by Dutta et al. involving data from 3 randomized controlled trials (535 patients), remogliflozin was noted to have similar glycaemic efficacy (reduction in HbA1c and fasting glucose) as compared to dapagliflozin and pioglitazone. [9] A study concluded that concomitant administration of remogliflozin etabonate, either 500 mg or 750 mg BID (twice a day), with metformin 2000 mg BID was safe and effective in patients with type 2 diabetes mellitus during the observation period.[10]

Method of action

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Remogliflozin etabonate is a pro-drug of remogliflozin. Remogliflozin inhibits the sodium-glucose transport proteins (SGLT), which are responsible for glucose reabsorption in the kidney. Blocking this transporter causes blood glucose to be eliminated through the urine.[11] Remogliflozin is selective for SGLT2.

See also

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References

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  1. ^ Markham, A.J.D., Remogliflozin etabonate: first global approval. 2019. 79(10): p. 1157-1161.
  2. ^ Statement on a nonproprietory name adopted by the USAN council
  3. ^ "Avolynt Announces Completion of Phase 2b BRID Study of SGLT2 Inhibitor Remogliflozin-Etabonate" (Press release). Avolynt, Inc. Retrieved July 24, 2018.
  4. ^ Mohan, V., et al., Remogliflozin etabonate in the treatment of type 2 diabetes: design, development, and place in therapy. 2020: p. 2487-2501.
  5. ^ Mudaliar S, Armstrong DA, Mavian AA, O'Connor-Semmes R, Mydlow PK, Ye J, et al. (November 2012). "Remogliflozin etabonate, a selective inhibitor of the sodium-glucose transporter 2, improves serum glucose profiles in type 1 diabetes". Diabetes Care. 35 (11): 2198–200. doi:10.2337/dc12-0508. PMC 3476920. PMID 23011728.
  6. ^ Dobbins RL, O'Connor-Semmes R, Kapur A, Kapitza C, Golor G, Mikoshiba I, et al. (January 2012). "Remogliflozin etabonate, a selective inhibitor of the sodium-dependent transporter 2 reduces serum glucose in type 2 diabetes mellitus patients". Diabetes, Obesity & Metabolism. 14 (1): 15–22. doi:10.1111/j.1463-1326.2011.01462.x. PMID 21733056. S2CID 23372554.
  7. ^ Sykes AP, O'Connor-Semmes R, Dobbins R, Dorey DJ, Lorimer JD, Walker S, et al. (January 2015). "Randomized trial showing efficacy and safety of twice-daily remogliflozin etabonate for the treatment of type 2 diabetes". Diabetes, Obesity & Metabolism. 17 (1): 94–7. doi:10.1111/dom.12391. PMID 25223369. S2CID 6436562.
  8. ^ Sykes AP, Kemp GL, Dobbins R, O'Connor-Semmes R, Almond SR, Wilkison WO, et al. (January 2015). "Randomized efficacy and safety trial of once-daily remogliflozin etabonate for the treatment of type 2 diabetes". Diabetes, Obesity & Metabolism. 17 (1): 98–101. doi:10.1111/dom.12393. PMID 25238025. S2CID 25280330.
  9. ^ Dutta D, Jindal R, Mehta D, Khandelwal D, Sharma M (Nov 2021). "Efficacy and safety of novel sodium glucose cotransporter-2 inhibitor remogliflozin in the management of type 2 diabetes mellitus: A systematic review and meta-analysis". Diabetes Metab Syndr. 15 (6): 102315. doi:10.1016/j.dsx.2021.102315. PMID 34700292. S2CID 239491862.
  10. ^ Dobbins, R., et al., Assessment of safety and tolerability of remogliflozin etabonate (GSK189075) when administered with total daily dose of 2000 mg of metformin. 2021. 22: p. 1-11.
  11. ^ "Molecule of the Month: Dapagliflozin". Prous Science. November 2007. Archived from the original on January 6, 2008.
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