Remogliflozin Etabonate in the Treatment of Type 2 Diabetes: Design, Development, and Place in Therapy

References

• ZhengY, LeySH, HuFB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol. 2017;14(2):88. doi:10.1038/nrendo.2017.15129219149
   PubMed Web of Science ®Google Scholar
• International Diabetes Federation. IDF diabetes atlas 9th edition; 2019 Available from: https://www.diabetesatlas.org/en/resources/.Accessed 1220, 2019.
   Google Scholar
• ChoiCI. Sodium-glucose cotransporter 2 (SGLT2) inhibitors from natural products: discovery of next-generation antihyperglycemic agents. Molecules. 2016;21(9):1136. doi:10.3390/molecules21091136
   PubMed Web of Science ®Google Scholar
• DeyL, AtteleAS, YuanCS. Alternative therapies for type 2 diabetes. Altern Med Rev. 2002;7(1):45–58.11896745
   PubMedGoogle Scholar
• Tamez-PerezHE, Gonzalez-GuajardoEE, Tamez-PenaAL. Consensus statement by The American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm - 2019 executive summary. Endocr Pract. 2019;25(6):622.31242125
   PubMed Web of Science ®Google Scholar
• KapurA, O’Connor-SemmesR, HusseyEK, et al. First human dose-escalation study with remogliflozinetabonate, a selective inhibitor of the sodium-glucose transporter 2 (SGLT2), in healthy subjects and in subjects with type 2 diabetes mellitus. BMC Pharmacol Toxicol. 2013;14(1):26. doi:10.1186/2050-6511-14-2623668634
   PubMed Web of Science ®Google Scholar
• NealB, PerkovicV, MahaffeyKW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377(7):644–657. doi:10.1056/NEJMoa161192528605608
   PubMed Web of Science ®Google Scholar
• ZinmanB, WannerC, LachinJM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117–2128. doi:10.1056/NEJMoa150472026378978
   PubMed Web of Science ®Google Scholar
• WiviottSD, RazI, BonacaMP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019;380(4):347–357. doi:10.1056/NEJMoa181238930415602
   PubMed Web of Science ®Google Scholar
• ZelnikerTA, WiviottSD, RazI, et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet. 2019;393(10166):31–39. doi:10.1016/S0140-6736(18)32590-X30424892
   PubMed Web of Science ®Google Scholar
• Santos-GallegoCG, Requena-IbanezJA, San AntonioR, et al. Empagliflozin ameliorates adverse left ventricular remodeling in nondiabetic heart failure by enhancing myocardial energetics. J Am Coll Cardiol. 2019;73(15):1931–1944. doi:10.1016/j.jacc.2019.01.05630999996
   PubMed Web of Science ®Google Scholar
• Santos-GallegoCG, Garcia-RoperoA, ManciniD, et al. Rationale and design of the EMPA-TROPISM trial (ATRU-4): are the “cardiac benefits” of empagliflozin independent of its hypoglycemic activity? Cardiovasc Drugs Ther. 2019;33(1):87–95. doi:10.1007/s10557-018-06850-030675708
   PubMed Web of Science ®Google Scholar
• DaviesMJ, D’AlessioDA, FradkinJ, et al. Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2018;61(12):2461–2498. doi:10.1007/s00125-018-4729-530288571
   PubMed Web of Science ®Google Scholar
• O’Connor-SemmesR, WalkerS, KapurA, et al. Pharmacokinetics and pharmacodynamics of the SGLT2 inhibitor remogliflozinetabonate in subjects with mild and moderate renal impairment. Drug Metab Dispos. 2015;43(7):1077–1083. doi:10.1124/dmd.114.06282825934577
   PubMed Web of Science ®Google Scholar
• JoshiS, GudiG, MenonVC, et al. An open-label, single-period, two-stage, single oral dose pharmacokinetic study of RemogliflozinEtabonate tablet 100 and 250 mg in healthy asian indian male subjects under fasting and fed conditions. Clin Pharmacokinet. 2020;59(3):349–357. doi:10.1007/s40262-019-00819-431583610
   PubMed Web of Science ®Google Scholar
• SigafoosJF, BowersGD, CastellinoS, et al. Assessment of the drug interaction risk for remogliflozinetabonate, a sodium-dependent glucose cotransporter-2 inhibitor: evidence from in vitro, human mass balance, and ketoconazole interaction studies. Drug Metab Dispos. 2012;40(11):2090–2101. doi:10.1124/dmd.112.04725822851617
   PubMed Web of Science ®Google Scholar
• MarkhamA. RemogliflozinEtabonate: first global approval. Drugs. 2019;79(10):1157–1161. doi:10.1007/s40265-019-01150-931201711
   PubMed Web of Science ®Google Scholar
• RosenstockJ, JelaskaA, FrappinG, et al. Improved glucose control with weight loss, lower insulin doses, and no increased hypoglycemia with empagliflozin added to titrated multiple daily injections of insulin in obese inadequately controlled type 2 diabetes. Diabetes Care. 2014;37(7):1815–1823. doi:10.2337/dc13-305524929430
   PubMed Web of Science ®Google Scholar
• FujimoriY, KatsunoK, NakashimaI, Ishikawa-TakemuraY, FujikuraH, IsajiM. Remogliflozinetabonate, in a novel category of selective low-affinity sodium glucose cotransporter (SGLT2) inhibitors, exhibits antidiabetic efficacy in rodent models. J Pharmacol Exp Ther. 2008;327(1):268–276. doi:10.1124/jpet.108.14021018583547
   PubMed Web of Science ®Google Scholar
• DharmalingamM, AravindSR, ThackerH, et al. Efficacy and safety of RemogliflozinEtabonate, a new sodium glucose co-transporter-2 inhibitor, in patients with type 2 diabetes mellitus: a 24-week, randomized, double-blind, active-controlled trial. Drugs. 2020;11:1–4.
   Google Scholar
• Central Drugs Standard Control Organization (CDSCO). List of new drugs approved in the year; 2019 till date Available from: https://cdsco.gov.in/opencms/opencms/system/modules/CDSCO.WEB/elements/download_file_division.jsp?num_id=NDY2Nw==. Accessed 724, 2019.
   Google Scholar
• National Center for Biotechnology Information. PubChem database. Remogliflozinetabonate, CID=9871420. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Remogliflozin-etabonate. Accessed 327, 2020.
   Google Scholar
• O’Connor‐SemmesRL, SandeferEP, HusseyEK, et al. Regional gastrointestinal delivery of remogliflozinetabonate in humans. Biopharm Drug Dispos. 2013;34(2):79–86. doi:10.1002/bdd.182423111980
   PubMed Web of Science ®Google Scholar
• GlaxoSmithKline. A phase I single-dose PK study in healthy subjects and postmenopausal females. Clinical study report (KGT-1101). 2006 ( unpublished report)
   Google Scholar
• DobbinsRL, O’Connor‐SemmesR, KapurA, et al. Remogliflozinetabonate, a selective inhibitor of the sodium‐dependent transporter 2 reduces serum glucose in type 2 diabetes mellitus patients. Diabetes Obes Metab. 2012;14(1):15–22. doi:10.1111/j.1463-1326.2011.01462.x21733056
   PubMed Web of Science ®Google Scholar
• GlaxoSmithKline. A randomized, placebo-controlled, double-blind, repeat dose, dose escalation trial to investigate the safety, tolerability and pharmacokinetics of supratherapeutic doses of GSK189075 administered for 3 days in healthy volunteers. clinical study report (KG2109799). 2007 ( unpublished report)
   Google Scholar
• GlaxoSmithKline. A study to evaluate and study drug levels in blood plasma when giving high doses of GSK189075 to healthy volunteers; 2007 Available from: https://clinicaltrials.gov/ct2/show/NCT00501930. NLM Identifier-NCT00501930 Accessed 322, 2020.
   Google Scholar
• GlaxoSmithKline.A phase I single-dose PK study in healthy subjects and postmenopausal females. Clinical study report (KGT-1102). 2007 ( unpublished report)
   Google Scholar
• GlaxoSmithKline. PK of concomitant administration of GSK189075 with metformin in subjects with type 2 diabetes mellitus. Clinical study report (KG2110243). 2008 ( unpublished report)
   Google Scholar
• GlaxoSmithKline. A study to assess the safety and tolerability of GSK189075 when given with a total daily dose of>/ 2000mg of metformin; 2007 Available from:https://clinicaltrials.gov/ct2/show/NCT00519480. NLM Identifier- NCT00519480 Accessed 322, 2020.
   Google Scholar
• GlaxoSmithKline. A study to compare effects of GSK189075 in combination with either furosemide or hydrochlorothiazide; 2008 Available from: https://clinicaltrials.gov/ct2/show/NCT00671424. NLM Identifier- NCT00671424 Accessed 322, 2020.
   Google Scholar
• GlaxoSmithKline. An evaluation of the safety, tolerability, and pharmacodynamics effects of GSK189075 when administered with furosemide or hydrochlorothiazide. Clinical study report (KG2105251). 2008 ( unpublished report)
   Google Scholar
• GlaxoSmithKline.A study to assess the safety of repeated doses of GSK189075 and WELLBUTRIN SR in healthy male subjects; 2008 Available from: https://clinicaltrials.gov/ct2/show/NCT00625859. NLM Identifier- NCT00625859 Accessed 322, 2020.
   Google Scholar
• GlaxoSmithKline. A double-blind, randomized, 6-sequence, 3-period, crossover drug-drug interaction study to evaluate the pharmacokinetics of WELLBUTRIN SR and GSK189075, when co-administered or administered alone in healthy male volunteers. Clinical study report (KGW111083). 2008 ( unpublished report)
   Google Scholar
• Remogliflozinetabonate [ package insert]. Mumbai (India): Glenmark Pharmaceuticals Ltd; 4 2019.
   Google Scholar
• GlaxoSmithKline. A study of the effects of GSK189075 on PK profiles of an oral contraceptive pill when given to healthy female volunteers; 2009 Available from: https://clinicaltrials.gov/ct2/show/NCT00504816. NLM Identifier- NCT00504816 Accessed 322, 2020.
   Google Scholar
• GlaxoSmithKline. A randomized, double-blind, placebo-controlled, cross-over trial to investigate the effect of GSK189075 on cardiac repolarization as compared to placebo and a single dose of moxifloxacin in healthy adult subjects. Clinical study report (KG2107489). 2008 ( unpublished report)
   Google Scholar
• GlaxoSmithKline. A study to compare the effect on heart rhythm of 3 days of GSK189075, placebo, or moxifloxacin in healthy adults; 2007 Available from: https://clinicaltrials.gov/ct2/show/NCT00532610. NLM Identifier- NCT00532610 Accessed 322, 2020.
   Google Scholar
• NapolitanoA, MillerS, MurgatroydPR, et al. Exploring glycosuria as a mechanism for weight and fat mass reduction. A pilot study with remogliflozinetabonate and sergliflozinetabonate in healthy obese subjects. J Clin Transl Endocrinol. 2014;1(1):e3–8. doi:10.1016/j.jcte.2013.12.00129235586
   PubMedGoogle Scholar
• MudaliarS, ArmstrongDA, MavianAA, et al. Remogliflozinetabonate, a selective inhibitor of the sodium-glucose transporter 2, improves serum glucose profiles in type 1 diabetes. Diabetes Care. 2012;35(11):2198–2200. doi:10.2337/dc12-050823011728
   PubMed Web of Science ®Google Scholar
• SykesAP, O’Connor‐SemmesR, DobbinsR, et al. Randomized trial showing efficacy and safety of twice‐daily remogliflozinetabonate for the treatment of type 2 diabetes. Diabetes Obes Metab. 2015;17(1):94–97. doi:10.1111/dom.1239125223369
   PubMed Web of Science ®Google Scholar
• SykesAP, KempGL, DobbinsR, et al. Randomized efficacy and safety trial of once‐daily remogliflozinetabonate for the treatment of type 2 diabetes. Diabetes Obes Metab. 2015;17(1):98–101. doi:10.1111/dom.1239325238025
   PubMed Web of Science ®Google Scholar
• BHV Pharma. Safety and efficacy of biphasic RemogliflozinEtabonate in the treatment of type 2 diabetes (BRID); 2015 Available from: https://clinicaltrials.gov/ct2/show/NCT02537470. NLM Identifier- NCT02537470 Accessed 320, 2020.
   Google Scholar
• Accesswire. Avolynt, Inc. announces positive topline data for phase 2b BRID study of SGLT2 remogliflozin [internet] North Carolina; 12 2016 [cited 331, 2020]. Available from: https://www.accesswire.com/451309/Avolynt-Inc-Announces-Positive-Topline-Data-for-Phase-2b-BRID-Study-of-SGLT2-Remogliflozin.
   Google Scholar
• SinghAK, SinghR. Sodium-glucose co-transporter-2 inhibitors as add-on therapy to insulin: rationale and evidences. Expert Rev Clin Pharmacol. 2016;9(3):409–418. doi:10.1586/17512433.2016.113112126732230
   PubMed Web of Science ®Google Scholar
• ScheenAJ. Pharmacokinetic and pharmacodynamic profile of empagliflozin, a sodium glucose co-transporter 2 inhibitor. Clin Pharmacokinet. 2014;53(3):213–225. doi:10.1007/s40262-013-0126-x24430725
   PubMed Web of Science ®Google Scholar
• KasichayanulaS, LiuX, LaCretaF, GriffenSC, BoultonDW. Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-transporter type 2. Clin Pharmacokinet. 2014;53(1):17–27. doi:10.1007/s40262-013-0104-324105299
   PubMed Web of Science ®Google Scholar
• DevineniD, CurtinCR, PolidoriD, et al. Pharmacokinetics and pharmacodynamics of canagliflozin, a sodium glucose co‐transporter 2 inhibitor, in subjects with type 2 diabetes mellitus. J Clin Pharmacol. 2013;53(6):601–610. doi:10.1002/jcph.8823670707
   PubMed Web of Science ®Google Scholar
• MiaoZ, NucciG, AminN, et al. Pharmacokinetics, metabolism, and excretion of the antidiabetic agent ertugliflozin (PF-04971729) in healthy male subjects. Drug Metab Dispos. 2013;41(2):445–456. doi:10.1124/dmd.112.04955123169609
   PubMed Web of Science ®Google Scholar
• JARDIANCE® (empagliflozin) [ package insert on the Internet]. U.S. Food and Drug Administration: BoehringerIngelheim Pharmaceuticals; 1 2020 Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/204629s023lbl.pdf. Accessed 322, 2020.
   Google Scholar
• INVOKANA (canagliflozin) [ package insert on the Internet]. U.S. Food and Drug Administration: Janssen Pharmaceuticals; 1 2020 Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/204042s036lbl.pdf. Accessed 322, 2020.
   Google Scholar
• FARXIGA® (dapagliflozin) [ package insert on the Internet]. U.S. Food and Drug Administration: AstraZeneca Pharmaceuticals LP; 1 2020 Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/202293s022lbl.pdf. Accessed 322, 2020.
   Google Scholar
• STEGLATRO™ (ertugliflozin) [ package insert on the Internet]. U.S. Food and Drug Administration: Merck & Co.; 1 2020 Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/209803s002lbl.pdf. Accessed 322, 2020.
   Google Scholar
• FalaL. Jardiance (empagliflozin), an SGLT2 inhibitor, receives FDA approval for the treatment of patients with type 2 diabetes. Am Health Drug Benefits. 2015;8(Spec Feature):92.26629271
   PubMedGoogle Scholar
• FerranniniE, RamosSJ, SalsaliA, TangW, ListJF. Dapagliflozin monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise: a randomized, double-blind, placebo-controlled, phase 3 trial. Diabetes Care. 2010;33(10):2217–2224. doi:10.2337/dc10-061220566676
   PubMed Web of Science ®Google Scholar
• StenlöfK, CefaluWT, KimKA, et al. Efficacy and safety of canagliflozin monotherapy in subjects with type 2 diabetes mellitus inadequately controlled with diet and exercise. Diabetes Obes Metab. 2013;15(4):372–382. doi:10.1111/dom.1205423279307
   PubMed Web of Science ®Google Scholar