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.
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| Routes of administration | By mouth |
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| Metabolism | Remoglifozin 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] |
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| Formula | C26H38N2O9 |
| Molar mass | 522.595 g·mol−1 |
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Clinical trials
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
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.