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2000
Volume 17, Issue 1
  • ISSN: 2589-9775
  • E-ISSN: 2589-9783

Abstract

SGLT2 (Sodium-Glucose Co-transporter 2) inhibitors, also known as gliflozin class, are a novel family of oral drugs being used to treat type 2 diabetes. SGLT2 inhibitors can work alone or in conjunction with other medications. This class includes five drugs, including canagliflozin, ertugliflozin, sotagliflozin, dapagliflozin, and empagliflozin. SGLT2 inhibitors inhibit the SGLT2 cotransporter in the proximal tubules of the kidney, reducing glucose and sodium reabsorption. It promotes the elimination of sugar in urine (diabetes mellitus) and lowers blood sugar levels. SGLT2 inhibitors also have pleiotropic effects on cardiac and renal function, broadening their therapeutic applications in heart failure. Despite the clinical benefits, regulators have placed secondary warnings in product information since the medications first hit the market. SGLT2 inhibitors, in particular, have had a significant impact on a variety of risk factors. This can lead to hypoglycaemia, urinary tract infections, diabetic ketoacidosis, lower limb amputation, and fractures. Although some of these events are uncommon, they can lead to severe and deadly consequences; therefore, patients must be closely monitored. In general, SLGT2 inhibitors are an efficient diabetes treatment with strong cardiovascular and renal protection and a favourable safety overview. This review sought to summarise the safety overview of commercially available SGLT2 inhibitors.

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2024-08-16
2025-05-03
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References

  1. GhezziC. LooD.D.F. WrightE.M. Physiology of renal glucose handling via SGLT1, SGLT2 and GLUT2.Diabetologia201861102087209710.1007/s00125‑018‑4656‑530132032
    [Google Scholar]
  2. MudaliarS. PolidoriD. ZambrowiczB. HenryR.R. Sodiumglucose cotransporter inhibitors: effects on renal and intestinal glucose transport: from bench to bedside.Diabetes Care201538122344235310.2337/dc15‑064226604280
    [Google Scholar]
  3. GalloL.A. WrightE.M. VallonV. Probing SGLT2 as a therapeutic target for diabetes: Basic physiology and consequences.Diab. Vasc. Dis. Res.2015122788910.1177/147916411456199225616707
    [Google Scholar]
  4. PoulsenS.B. FentonR.A. RiegT. Sodium-glucose cotransport.Curr. Opin. Nephrol. Hypertens.201524546346910.1097/MNH.000000000000015226125647
    [Google Scholar]
  5. RiegT. MasudaT. GerasimovaM. Increase in SGLT1-mediated trans-port explains renal glucose reabsorption during genetic and pharmacological SGLT2 inhibition in euglycemia.Am J Physiol Renal Physiol.2014306F188F193
    [Google Scholar]
  6. HenryR.R. RosenstockJ. EdelmanS. MudaliarS. ChalamandarisA.G. KasichayanulaS. BogleA. IqbalN. ListJ. GriffenS.C. Exploring the potential of the SGLT2 inhibitor dapagliflozin in type 1 diabetes: a randomized, double-blind, placebo-controlled pilot study.Diabetes Care201538341241910.2337/dc13‑295525271207
    [Google Scholar]
  7. NortonL. ShannonC.E. FourcaudotM. HuC. WangN. RenW. SongJ. Abdul-GhaniM. DeFronzoR.A. RenJ. JiaW.   Sodium-glucose   co-transporter (SGLT) and glucose transporter (GLUT) expression in the kidney of type 2 diabetic subjects.Diabetes Obes. Metab.20171991322132610.1111/dom.1300328477418
    [Google Scholar]
  8. SoliniA. RossiC. MazzantiC.M. ProiettiA. KoepsellH. FerranniniE. You have full text access to this contentSGLT2 and SGLT1 renal expression in patients with type 2 diabetes.Diabetes Obes. Metab.201710.1111/dom.12970
    [Google Scholar]
  9. WangX.X. LeviJ. LuoY. MyakalaK. Herman-EdelsteinM. QiuL. WangD. PengY. GrenzA. LuciaS. DobrinskikhE. D’AgatiV.D. KoepsellH. KoppJ.B. RosenbergA.Z. LeviM. SGLT2 Protein Expression Is Increased in Human Diabetic Nephropathy.J. Biol. Chem.2017292135335534810.1074/jbc.M117.77952028196866
    [Google Scholar]
  10. GembardtF. BartaunC. JarzebskaN. MayouxE. TodorovV.T. HohensteinB. HugoC. The SGLT2 inhibitor empagliflozin ameliorates early features of diabetic nephropathy in BTBR ob/ob type 2 diabetic mice with and without hypertension.Am. J. Physiol. Renal Physiol.20143073F317F32510.1152/ajprenal.00145.201424944269
    [Google Scholar]
  11. TakebayashiK. HaraK. TerasawaT. NaruseR. SuetsuguM. TsuchiyaT. InukaiT. Effect of canagliflozin on circulating active GLP-1 levels in patients with type 2 diabetes: a randomized trial.Endocr. J.201764992393110.1507/endocrj.EJ17‑006528824041
    [Google Scholar]
  12. van BommelE.J.M. MuskietM.H.A. TonneijckL. KramerM.H.H. NieuwdorpM. van RaalteD.H. SGLT2 inhibition in the diabetic kidneyfrom mechanisms to clinical outcome.Clin. J. Am. Soc. Nephrol.201712470071010.2215/CJN.0608061628254770
    [Google Scholar]
  13. HummelC.S. LuC. LooD.D.F. HirayamaB.A. VossA.A. WrightE.M. Glucose transport by human renal Na +/d -glucose cotransporters SGLT1 and SGLT2.Am. J. Physiol. Cell Physiol.20113001C14C2110.1152/ajpcell.00388.201020980548
    [Google Scholar]
  14. EvenepoelP. MeijersB. MasereeuwR. LowensteinJ. Effects of an SGLT inhibitor on the production, toxicity, and elimination of gutderived uremic toxins: a call for additional evidence.Toxins (Basel)202214321010.3390/toxins1403021035324707
    [Google Scholar]
  15. NauckM. Update on developments with SGLT2 inhibitors in the management of type 2 diabetes.Drug Des. Devel. Ther.201481335138010.2147/DDDT.S5077325246775
    [Google Scholar]
  16. Fonseca-CorreaJ.I. Correa-RotterR. Sodium-glucose cotransporter 2 inhibitors mechanisms of action: a review.Front. Med. (Lausanne)2021877786110.3389/fmed.2021.77786134988095
    [Google Scholar]
  17. HelalI. Fick-BrosnahanG.M. Reed-GitomerB. SchrierR.W. Glomerular hyperfiltration: definitions, mechanisms and clinical implications.Nat. Rev. Nephrol.20128529330010.1038/nrneph.2012.1922349487
    [Google Scholar]
  18. SenT. HeerspinkH.J.L. A kidney perspective on the mechanism of action of sodium glucose co-transporter 2 inhibitors.Cell Metab.202133473273910.1016/j.cmet.2021.02.01633691091
    [Google Scholar]
  19. DenicA. MathewJ. LermanL.O. LieskeJ.C. LarsonJ.J. AlexanderM.P. PoggioE. GlassockR.J. RuleA.D. Single-nephron glomerular filtration rate in healthy adults.N. Engl. J. Med.2017376242349235710.1056/NEJMoa161432928614683
    [Google Scholar]
  20. LimB.J. YangJ.W. ZouJ. ZhongJ. MatsusakaT. PastanI. ZhangM.Z. HarrisR.C. YangH.C. FogoA.B. Tubulointerstitial fibrosis can sensitize the kidney to subsequent glomerular injury.Kidney Int.20179261395140310.1016/j.kint.2017.04.01028709637
    [Google Scholar]
  21. MimaA. Sodium-glucose cotransporter 2 inhibitors in patients with non-diabetic chronic kidney disease.Adv. Ther.20213852201221210.1007/s12325‑021‑01735‑533860925
    [Google Scholar]
  22. O’NeillJ. FaschingA. PihlL. PatinhaD. FranzénS. PalmF. Acute SGLT inhibition normalizes O2 tension in the renal cortex but causes hypoxia in the renal medulla in anaesthetized control and diabetic rats.Am J Physiol Renal Physiol.20153093F227F234
    [Google Scholar]
  23. ThomsonSC. RiegT. MiracleC. MansouryH. WhaleyJ. VallonV Acute and chronic effects of SGLT2 blockade on glomerular and tubular function in the early diabetic rat.Am J Physiol Regul Integr Comp Physiol.20123021R75R8310.1152/ajpregu.00357.2011
    [Google Scholar]
  24. LaytonAT. VallonV. SGLT2 inhibition in a kidney with reduced nephron number: modeling and analysis of solute transport and metabolism.Am J Physiol Renal Physiol.20183145F969F98410.1152/ajprenal.00551.2017
    [Google Scholar]
  25. CherneyD.Z.I. PerkinsB.A. SoleymanlouN. MaioneM. LaiV. LeeA. FaganN.M. WoerleH.J. JohansenO.E. BroedlU.C. von EynattenM. Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus.Circulation2014129558759710.1161/CIRCULATIONAHA.113.00508124334175
    [Google Scholar]
  26. YaleJ.F. BakrisG. CariouB. YueD. David-NetoE. XiL. FigueroaK. WajsE. UsiskinK. MeiningerG. Efficacy and safety of canagliflozin in subjects with type 2 diabetes and chronic kidney disease.Diabetes Obes. Metab.201315546347310.1111/dom.1209023464594
    [Google Scholar]
  27. NiL. YuanC. ChenG. ZhangC. WuX. SGLT2i: beyond the glucose-lowering effect.Cardiovasc. Diabetol.20201919810.1186/s12933‑020‑01071‑y32590982
    [Google Scholar]
  28. MudaliarS. AllojuS. HenryR.R. Can a shift in fuel energetics explain the beneficial cardiorenal outcomes in the EMPA-REG outcome study? A unifying hypothesis.Diabetes Care20163971115112210.2337/dc16‑054227289124
    [Google Scholar]
  29. RajasekeranH. CherneyD.Z. LovshinJ.A. Do effects of sodium–glucose cotransporter-2 inhibitors in patients with diabetes give insight into potential use in non-diabetic kidney disease?Curr. Opin. Nephrol. Hypertens.201726535836710.1097/MNH.000000000000034328582367
    [Google Scholar]
  30. Abdul-GhaniM.A. DeFronzoR.A. NortonL. Novel hypothesis to explain why SGLT2 inhibitors inhibit only 30-50% of filtered glucose load in humans.Diabetes201362103324332810.2337/db13‑060424065789
    [Google Scholar]
  31. MimaA. Renal protection by sodium-glucose cotransporter 2 inhibitors and its underlying mechanisms in diabetic kidney disease.J. Diabetes Complications201832772072510.1016/j.jdiacomp.2018.04.01129880432
    [Google Scholar]
  32. CefaluW.T. StenlöfK. LeiterL.A. WildingJ.P.H. BlondeL. PolidoriD. XieJ. SullivanD. UsiskinK. CanovatchelW. MeiningerG. Effects of canagliflozin on body weight and relationship to HbA1c and blood pressure changes in patients with type 2 diabetes.Diabetologia20155861183118710.1007/s00125‑015‑3547‑225813214
    [Google Scholar]
  33. BruntonS.A. The potential role of sodium glucose co-transporter 2 inhibitors in the early treatment of type 2 diabetes mellitus.Int. J. Clin. Pract.201569101071108710.1111/ijcp.1267526147213
    [Google Scholar]
  34. Prescribing information, INVOKANA.2016Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/204042s011lbl.pdf(accessed on 31-7-2024)
  35. Prescribing information, FARXIGA.2015Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/202293s008lbl.pdf(accessed on 31-7-2024)
  36. Prescribing information, JARDIANCE.2016Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/204629s005lbl.pdf(accessed on 31-7-2024)
  37. ScheenA.J. SGLT2 inhibition: efficacy and safety in type 2 diabetes treatment.Expert Opin. Drug Saf.201514121879190410.1517/14740338.2015.110016726513131
    [Google Scholar]
  38. YangXP. LaiD. ZhongXY. ShenHP. HuangYL. Efficacy and safety of canagliflozin in subjects with type 2 diabetes: systematic review and meta-analysis.Eur J Clin Pharmacol2014701149115810.1007/s00228‑014‑1730‑x
    [Google Scholar]
  39. ZhangM. ZhangL. WuB. SongH. AnZ. LiS. Dapagliflozin treatment for type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials.Diabetes Metab. Res. Rev.201430320422110.1002/dmrr.247924115369
    [Google Scholar]
  40. LiakosA. KaragiannisT. AthanasiadouE. SarigianniM. MainouM. PapatheodorouK. BekiariE. TsapasA. Efficacy and safety of empagliflozin for type 2 diabetes: a systematic review and meta-analysis.Diabetes Obes. Metab.2014161098499310.1111/dom.1230724766495
    [Google Scholar]
  41. ZinmanB. WannerC. LachinJ.M. FitchettD. BluhmkiE. HantelS. MattheusM. DevinsT. JohansenO.E. WoerleH.J. BroedlU.C. InzucchiS.E. EMPA-REG OUTCOME Investigators Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes.N. Engl. J. Med.2015373222117212810.1056/NEJMoa150472026378978
    [Google Scholar]
  42. KohlerS. SalsaliA. HantelS. KaspersS. WoerleH.J. KimG. BroedlU.C. Safety and tolerability of empagliflozin in patients with type 2 diabetes.Clin. Ther.201638612991313Epub ahead of print10.1016/j.clinthera.2016.03.03127085585
    [Google Scholar]
  43. GeerlingsS. FonsecaV. Castro-DiazD. ListJ. ParikhS. Genital and urinary tract infections in diabetes: Impact of pharmacologically-induced glucosuria.Diabetes Res. Clin. Pract.2014103337338110.1016/j.diabres.2013.12.05224529566
    [Google Scholar]
  44. NyirjesyP. ZhaoY. WaysK. UsiskinK. Evaluation of vulvovaginal symptoms and Candida colonization in women with type 2 diabetes mellitus treated with canagliflozin, a sodium glucose co-transporter 2 inhibitor.Curr. Med. Res. Opin.20122871173117810.1185/03007995.2012.69705322632452
    [Google Scholar]
  45. JohnssonK.M. PtaszynskaA. SchmitzB. SuggJ. ParikhS.J. ListJ.F. Vulvovaginitis and balanitis in patients with diabetes treated with dapagliflozin.J. Diabetes Complications201327547948410.1016/j.jdiacomp.2013.04.01223806570
    [Google Scholar]
  46. WhalenK. MillerS. OngeE.S. The role of sodium-glucose co-transporter 2 inhibitors in the treatment of type 2 diabetes.Clin. Ther.20153761150116610.1016/j.clinthera.2015.03.00425891804
    [Google Scholar]
  47. NyirjesyP. SobelJ.D. FungA. MayerC. CapuanoG. WaysK. UsiskinK. Genital mycotic infections with canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus: a pooled analysis of clinical studies.Curr. Med. Res. Opin.20143061109111910.1185/03007995.2014.89092524517339
    [Google Scholar]
  48. ParveenR. AgarwalN.B. KaushalN. MaliG. RaisuddinS. Efficacy and safety of canagliflozin in type 2 diabetes mellitus: systematic review of randomized controlled trials.Expert Opin. Pharmacother.201617110511510.1517/14656566.2016.110962926650511
    [Google Scholar]
  49. PtaszynskaA. JohnssonK.M. ParikhS.J. de BruinT.W.A. ApanovitchA.M. ListJ.F. Safety profile of dapagliflozin for type 2 diabetes: pooled analysis of clinical studies for overall safety and rare events.Drug Saf.2014371081582910.1007/s40264‑014‑0213‑425096959
    [Google Scholar]
  50. BodeB. StenlöfK. HarrisS. SullivanD. FungA. UsiskinK. MeiningerG. Long-term efficacy and safety of canagliflozin over 104 weeks in patients aged 55–80 years with type 2 diabetes.Diabetes Obes. Metab.201517329430310.1111/dom.1242825495720
    [Google Scholar]
  51. ScheenA.J. Pharmacokinetics, pharmacodynamics and clinical use of SGLT2 inhibitors in patients with type 2 diabetes mellitus and chronic kidney disease.Clin. Pharmacokinet.201554769170810.1007/s40262‑015‑0264‑425805666
    [Google Scholar]
  52. National Kidney Foundation K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification.Am. J. Kidney Dis.2002392Suppl. 1S1S26611904577
    [Google Scholar]
  53. BarnettA.H. MithalA. ManassieJ. JonesR. RattundeH. WoerleH.J. BroedlU.C. EMPA-REG RENAL trial investigators Efficacy and safety of empagliflozin added to existing antidiabetes treatment in patients with type 2 diabetes and chronic kidney disease: a randomised, double-blind, placebo-controlled trial.Lancet Diabetes Endocrinol.20142536938410.1016/S2213‑8587(13)70208‑024795251
    [Google Scholar]
  54. KohanD.E. FiorettoP. JohnssonK. ParikhS. PtaszynskaA. YingL. The effect of dapagliflozin on renal function in patients with type 2 diabetes.J. Nephrol.2016293391400Epub ahead of print10.1007/s40620‑016‑0261‑126894924
    [Google Scholar]
  55. PerkovicV. JardineM. VijapurkarU. MeiningerG. Renal effects of canagliflozin in type 2 diabetes mellitus.Curr. Med. Res. Opin.201531122219223110.1185/03007995.2015.109212826494163
    [Google Scholar]
  56. LiakosA. KaragiannisT. BekiariE. BouraP. TsapasA. Update on long-term efficacy and safety of dapagliflozin in patients with type 2 diabetes mellitus.Ther. Adv. Endocrinol. Metab.201562616710.1177/204201881456073525941564
    [Google Scholar]
  57. US Food and Drug Administration. Drug safety communications : FDA warns that SGLT2 inhibitors for diabetes may result in a serious condition of too much acid in the blood.Available from: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM446954.pdf(accessed on 31-7-2024)
  58. EMA confirms recommendations to minimise ketoacidosis risk with SGLT2 inhibitors for diabetes.Available from: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/referrals/SG LT2_inhibitors/human_referral_prac_000052.jsp&mid=WC0b01ac05805c516f(accessed on 31-7-2024)
  59. JabbourS. SeufertJ. ScheenA. BaileyC.J. KarupC. LangkildeA.M. Dapagliflozin in patients with type 2 diabetes mellitus: A pooled analysis of safety data from phase IIb/III clinical trials.Diabetes Obes. Metab.201820362062810.1111/dom.1312428950419
    [Google Scholar]
  60. EronduN. DesaiM. WaysK. MeiningerG. Diabetic ketoacidosis and related events in the canagliflozin type 2 diabetes clinical program.Diabetes Care20153891680168610.2337/dc15‑125126203064
    [Google Scholar]
  61. MonamiM. NreuB. ZannoniS. LualdiC. MannucciE. Effects of SGLT-2 inhibitors on diabetic ketoacidosis: A meta-analysis of randomised controlled trials.Diabetes Res. Clin. Pract.2017130536010.1016/j.diabres.2017.04.01728570924
    [Google Scholar]
  62. WiviottS.D. RazI. BonacaM.P. MosenzonO. KatoE.T. CahnA. SilvermanM.G. ZelnikerT.A. KuderJ.F. MurphyS.A. BhattD.L. LeiterL.A. McGuireD.K. WildingJ.P.H. RuffC.T. Gause-NilssonI.A.M. FredrikssonM. JohanssonP.A. LangkildeA.M. SabatineM.S. Dapagliflozin and cardiovascular outcomes in type 2 diabetes.N. Engl. J. Med.2019380434735710.1056/NEJMoa181238930415602
    [Google Scholar]
  63. WangY. DesaiM. RyanP.B. DeFalcoF.J. SchuemieM.J. StangP.E. BerlinJ.A. YuanZ. Incidence of diabetic ketoacidosis among patients with type 2 diabetes mellitus treated with SGLT2 inhibitors and other antihyperglycemic agents.Diabetes Res. Clin. Pract.2017128839010.1016/j.diabres.2017.04.00428448895
    [Google Scholar]
  64. FralickM. SchneeweissS. PatornoE. Risk of diabetic ketoacidosis after initiation of an SGLT2 inhibitor.N. Engl. J. Med.2017376232300230210.1056/NEJMc170199028591538
    [Google Scholar]
  65. KimY.G. JeonJ.Y. HanS.J. KimD.J. LeeK.W. KimH.J. Sodium-glucose co-transporter-2 inhibitors and the risk of ketoacidosis in patients with type 2 diabetes mellitus: A nationwide population-based cohort study.Diabetes Obes. Metab.20182081852185810.1111/dom.1329729569427
    [Google Scholar]
  66. JensenM.L. PerssonF. AndersenG.S. RidderstråleM. NolanJ.J. CarstensenB. JørgensenM.E. Incidence of ketoacidosis in the Danish type 2 diabetes population before and after introduction of sodium-glucose cotransporter 2 inhibitors-A nationwide, retrospective cohort study, 1995-2014.Diabetes Care2017405e57e5810.2337/dc16‑279328283564
    [Google Scholar]
  67. UedaP. SvanströmH. MelbyeM. EliassonB. SvenssonA.M. FranzénS. GudbjörnsdottirS. HveemK. JonassonC. PasternakB. Sodium glucose cotransporter 2 inhibitors and risk of serious adverse events: nationwide register based cohort study.BMJ2018363k436510.1136/bmj.k436530429124
    [Google Scholar]
  68. FadiniG.P. BonoraB.M. AvogaroA. SGLT2 inhibitors and diabetic ketoacidosis: data from the FDA Adverse Event Reporting System.Diabetologia20176081385138910.1007/s00125‑017‑4301‑828500396
    [Google Scholar]
  69. BlauJ.E. TellaS.H. TaylorS.I. RotherK.I. Ketoacidosis associated with SGLT2 inhibitor treatment: Analysis of FAERS data.Diabetes Metab. Res. Rev.2017338e292410.1002/dmrr.292428736981
    [Google Scholar]
  70. D’EliaJ. SegalA. BaylissG. WeinrauchL. Sodium–glucose cotransporter-2 inhibition and acidosis in patients with type 2 diabetes: a review of US FDA data and possible conclusions.Int. J. Nephrol. Renovasc. Dis.20171015315810.2147/IJNRD.S13589928670136
    [Google Scholar]
  71. MeyerE.J. GabbG. JesudasonD. SGLT2 inhibitor-associated euglycemic diabetic ketoacidosis: a South Australian clinical case series and Australian spontaneous adverse event notifications.Diabetes Care2018414e47e4910.2337/dc17‑172129440112
    [Google Scholar]
  72. Ado MoumouniA.N. RobinP. Hillaire-BuysD. FaillieJ.L. SGLT-2 inhibitors and ketoacidosis: a disproportionality analysis in the World Health Organization’s adverse drug reactions database.Fundam. Clin. Pharmacol.201832221622610.1111/fcp.1233429144574
    [Google Scholar]
  73. PetersA.L. BuschurE.O. BuseJ.B. CohanP. DinerJ.C. HirschI.B. Euglycemic diabetic ketoacidosis: a potential complication of treatment with sodium-glucose cotransporter 2 inhibition.Diabetes Care20153891687169310.2337/dc15‑084326078479
    [Google Scholar]
  74. OgawaW. SakaguchiK. Euglycemic diabetic ketoacidosis induced by SGLT2 inhibitors: possible mechanism and contributing factors.J. Diabetes Investig.20167213513810.1111/jdi.1240127042263
    [Google Scholar]
  75. TaylorS.I. BlauJ.E. RotherK.I. 104. Taylor SI, Blau JE, Rother KI. Perspective: SGLT2 inhibitors may predispose to ketoacidosis.J. Clin. Endocrinol. Metab.201510082849285210.1210/jc.2015‑1884
    [Google Scholar]
  76. MilderD.A. MilderT.Y. KamP.C.A. Sodium-glucose co-transporter type-2 inhibitors: pharmacology and peri-operative considerations.Anaesthesia20187381008101810.1111/anae.1425129529345
    [Google Scholar]
  77. DeNicolaL GabbaiFB, LibertiME, etal.Sodium/glucosecotransporter 2 inhibitors and prevention of diabetic nephropathy: targeting the renal tubule in diabetes.Am. J. Kidney Dis.201464162410.1053/j.ajkd.2014.02.01024673844
    [Google Scholar]
  78. Abdul-GhaniM.A. NortonL. DeFronzoR.A. Role of sodium-glucose cotransporter 2 (SGLT 2) inhibitors in the treatment of type 2 diabetes.Endocr. Rev.201132451553110.1210/er.2010‑002921606218
    [Google Scholar]
  79. PalmerB.F. CleggD.J. TaylorS.I. WeirM.R. Diabetic ketoacidosis, sodium glucose transporter-2 inhibitors and the kidney.J. Diabetes Complications20163061162116610.1016/j.jdiacomp.2016.05.00827240541
    [Google Scholar]
  80. HeerspinkH.J.L. PerkinsB.A. FitchettD.H. HusainM. CherneyD.Z.I. Sodium glucose cotransporter 2 inhibitors in the treatment of diabetes mellitus: Cardiovascular and kidney effects, potential mechanisms, and clinical applications.Circulation20161341075277210.1161/CIRCULATIONAHA.116.02188727470878
    [Google Scholar]
  81. WattsN.B. BilezikianJ.P. UsiskinK. EdwardsR. DesaiM. LawG. MeiningerG. Effects of canagliflozin on fracture risk in patients with type 2 diabetes mellitus.J. Clin. Endocrinol. Metab.2016101115716610.1210/jc.2015‑316726580237
    [Google Scholar]
  82. Lavalle-GonzálezF.J. JanuszewiczA. DavidsonJ. TongC. QiuR. CanovatchelW. MeiningerG. Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy: a randomised trial.Diabetologia201356122582259210.1007/s00125‑013‑3039‑124026211
    [Google Scholar]
  83. KohanD.E. FiorettoP. TangW. ListJ.F. Long-term study of patients with type 2 diabetes and moderate renal impairment shows that dapagliflozin reduces weight and blood pressure but does not improve glycemic control.Kidney Int.201485496297110.1038/ki.2013.35624067431
    [Google Scholar]
  84. BuseJ.B. WexlerD.J. TsapasA. RossingP. MingroneG. MathieuC. D’AlessioD.A. DaviesM.J. 2019 update to: 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).Diabetologia202063222122810.1007/s00125‑019‑05039‑w31853556
    [Google Scholar]
  85. BilezikianJ.P. WattsN.B. UsiskinK. PolidoriD. FungA. SullivanD. RosenthalN. Evaluation of bone mineral density and bone biomarkers in patients with type 2 diabetes treated with canagliflozin.J. Clin. Endocrinol. Metab.20161011445110.1210/jc.2015‑186026580234
    [Google Scholar]
  86. ForstT. GuthrieR. GoldenbergR. YeeJ. VijapurkarU. MeiningerG. SteinP. Efficacy and safety of canagliflozin over 52 weeks in patients with type 2 diabetes on background metformin and pioglitazone.Diabetes Obes. Metab.201416546747710.1111/dom.1227324528605
    [Google Scholar]
  87. TikkanenI. NarkoK. ZellerC. GreenA. SalsaliA. BroedlU.C. WoerleH.J. EMPA-REG BP Investigators Empagliflozin reduces blood pressure in patients with type 2 diabetes and hypertension.Diabetes Care201538342042810.2337/dc14‑109625271206
    [Google Scholar]
  88. VasilakouD. KaragiannisT. AthanasiadouE. MainouM. LiakosA. BekiariE. SarigianniM. MatthewsD.R. TsapasA. Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes: a systematic review and meta-analysis.Ann. Intern. Med.2013159426227410.7326/0003‑4819‑159‑4‑201308200‑0000724026259
    [Google Scholar]
  89. FerranniniE. SemanL. Seewaldt-BeckerE. HantelS. PinnettiS. WoerleH.J. A P hase IIb, randomized, placebo-controlled study of the SGLT2 inhibitor empagliflozin in patients with type 2 diabetes.Diabetes Obes. Metab.201315872172810.1111/dom.1208123398530
    [Google Scholar]
  90. ListJ.F. WooV. MoralesE. TangW. FiedorekF.T. Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes.Diabetes Care200932465065710.2337/dc08‑186319114612
    [Google Scholar]
  91. JardineM.J. ZhouZ. MahaffeyK.W. OshimaM. AgarwalR. BakrisG. BajajH.S. BullS. CannonC.P. CharytanD.M. de ZeeuwD. Di TannaG.L. GreeneT. HeerspinkH.J.L. LevinA. NealB. PollockC. QiuR. SunT. WheelerD.C. ZhangH. ZinmanB. RosenthalN. PerkovicV. CREDENCE Study Investigators Renal, cardiovascular, and safety outcomes of canagliflozin by baseline kidney function: A secondary analysis of the credence randomized trial.J. Am. Soc. Nephrol.20203151128113910.1681/ASN.201911116832354987
    [Google Scholar]
  92. InzucchiS.E. IlievH. PfarrE. ZinmanB. Empagliflozin and assessment of lower-limb amputations in the EMPA-REG OUTCOME trial.Diabetes Care2018411e4e510.2337/dc17‑155129133344
    [Google Scholar]
  93. MellanderA. BillgerM. JohnssonE. TräffA.K. YoshidaS. JohnssonK. Hypersensitivity events, including potentially hypersensitivity-related skin events, with dapagliflozin in patients with type 2 diabetes mellitus: a pooled analysis.Clin. Drug Investig.2016361192593310.1007/s40261‑016‑0438‑327461213
    [Google Scholar]
  94. RaschiE. ParisottoM. ForcesiE. La PlacaM. MarchesiniG. De PontiF. PoluzziE. Adverse events with sodium-glucose co-transporter-2 inhibitors: A global analysis of international spontaneous reporting systems.Nutr. Metab. Cardiovasc. Dis.201727121098110710.1016/j.numecd.2017.10.00829174026
    [Google Scholar]
  95. SakaedaT. KobuchiS. YoshiokaR. HarunaM. TakahataN. ItoY. SuganoA. FukuzawaK. HayaseT. HayakawaT. NakayamaH. TakaokaY. TohkinM. Susceptibility to serious skin and subcutaneous tissue disorders and skin tissue distribution of sodium-dependent glucose co-transporter type 2 (SGLT2) inhibitors.Int. J. Med. Sci.201815993794310.7150/ijms.2222430008607
    [Google Scholar]
  96. KumarS. CostelloA.J. ColmanP.G. Fournier’s gangrene in a man on empagliflozin for treatment of Type 2 diabetes.Diabet. Med.201734111646164810.1111/dme.1350828887847
    [Google Scholar]
  97. FDA warns about rare occurrences of a serious infection of the genital area with SGLT2 inhibitors for diabetes.Available from: https://www.fda.gov/Drugs/DrugSafety/ucm617360.htm(accessed on 31-7-2024)
  98. NealB. PerkovicV. MahaffeyK.W. de ZeeuwD. FulcherG. EronduN. ShawW. LawG. DesaiM. MatthewsD.R. CANVAS Program Collaborative Group Canagliflozin and cardiovascular and renal events in type 2 diabetes.N. Engl. J. Med.2017377764465710.1056/NEJMoa161192528605608
    [Google Scholar]
  99. ScheenA.J. Cardiovascular effects of new oral glucose-lowering agents: DPP4 and SGLT-2 inhibitors.Circ. Res.2018122101439145910.1161/CIRCRESAHA.117.31158829748368
    [Google Scholar]
  100. ZelnikerT.A. WiviottS.D. RazI. ImK. GoodrichE.L. BonacaM.P. MosenzonO. KatoE.T. CahnA. FurtadoR.H.M. BhattD.L. LeiterL.A. McGuireD.K. WildingJ.P.H. SabatineM.S. 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.Lancet201939310166313910.1016/S0140‑6736(18)32590‑X30424892
    [Google Scholar]
  101. CannonC.P. McGuireD.K. PratleyR. Dagogo-JackS. MancusoJ. HuyckS. CharbonnelB. ShihW.J. GalloS. MasiukiewiczU. GolmG. CosentinoF. LauringB. TerraS.G. VERTIS-CV Investigators Design and baseline characteristics of the eValuation of ERTugliflozin effIcacy and Safety CardioVascular outcomes trial (VERTIS-CV).Am. Heart J.2018206112310.1016/j.ahj.2018.08.01630290289
    [Google Scholar]
  102. KosiborodM. CavenderM.A. FuA.Z. Lower risk of heart failure and death in patients initiated on SGLT-2 inhibitors versus other glucose-lowering drugs: the CVD-REAL study (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors).Circulation201713624925910.1161/CIRCULATIONAHA.117.02919028522450
    [Google Scholar]
  103. (a KosiborodM LamCSP KohsakaS Lower cardiovascular risk associated with SGLT-2i in >400,000 patients: the CVD-REAL 2 study.J. Am. Coll. Cardiol.2018712628263910.1016/j.jacc.2018.03.00929540325
    [Google Scholar]
  104. (b RawshaniA. SvenssonA.M. RosengrenA. ZetheliusB. EliassonB. GudbjörnsdottirS. Impact of ethnicity on progress of glycaemic control in 131 935 newly diagnosed patients with type 2 diabetes: a nationwide observational study from the Swedish National Diabetes Register.BMJ open201556
    [Google Scholar]
  105. (a UdellJ.A. YuanZ. RushT. Cardiovascular outcomes and risks after initiation of a sodium glucose co-transporter 2 inhibitor: Results from the EASEL population-based cohort study.Circulation20181371450145910.1161/CIRCULATIONAHA.117.03122729133607
    [Google Scholar]
  106. (b DaveC.V. SchneeweissS. KimD. FralickM. TongA. PatornoE. Sodium–glucose cotransporter-2 inhibitors and the risk for severe urinary tract infections: a population-based cohort study.Annals of internal medicine.2019Aug201714248256
    [Google Scholar]
  107. (a ChenJ.Y. PanH.C. ShiaoC.C. Impact of SGLT2 inhibitors on patient outcomes: a network meta-analysis.Cardiovasc. Diabetol.202322129010.1186/s12933‑023‑02035‑837891550
    [Google Scholar]
  108. (b PatelD.K. StrongJ. The pleiotropic effects of sodium–glucose cotransporter-2 inhibitors: beyond the glycemic benefit.Diabetes Therapy. 2019 Oct;1017711792
    [Google Scholar]
  109. (a PatelS.M. KangY.M. ImK. Sodium-Glucose Cotransporter- 2 Inhibitors and Major Adverse Cardiovascular Outcomes: A SMART-C Collaborative Meta-Analysis.Circulation2024149231789180110.1161/CIRCULATIONAHA.124.06956838583093
    [Google Scholar]
  110. (b BrownA.J. GoldsworthyS.M. BarnesA.A. EilertM.M. TcheangL. DanielsD. MuirA.I. WigglesworthM.J. KinghornI. FraserN.J. PikeN.B. The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids.Journal of Biological Chemistry. 2003 Mar 28;278131131211319
    [Google Scholar]
  111. (a SolmonS. Meta-analysis strengthens evidence for SGLT2 inhibitors in patients with heart failure Prespecified meta-analysis of DELIVER and EMPEROR-Preserved presented in a Hot Line Session today at ESC Congress 2022. ESC Press 2022.2022
    [Google Scholar]
  112. (b BirkelandK.I. JørgensenM.E. CarstensenB. PerssonF. GulsethH.L. ThuressonM. FeniciP. NathansonD. NyströmT. ErikssonJ.W. BodegårdJ. Cardiovascular mortality and morbidity in patients with type 2 diabetes following initiation of sodium-glucose co-transporter-2 inhibitors versus other glucose-lowering drugs (CVD-REAL Nordic): a multinational observational analysis.The lancet Diabetes & endocrinology.2017Sep159709717
    [Google Scholar]
  113. (a MavrakanasT.A. TsoukasM.A. BrophyJ.M. SharmaA. GarianiK. SGLT-2 inhibitors improve cardiovascular and renal outcomes in patients with CKD: a systematic review and meta-analysis.Sci. Rep.20231311592210.1038/s41598‑023‑42989‑z37741858
    [Google Scholar]
  114. (b FriasJ.P. GujaC. HardyE. AhmedA. DongF. OhmanP. JabbourS.A. Exenatide once weekly plus dapagliflozin once daily versus exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled with metformin monotherapy (DURATION- 8): a 28 week, multicentre, double-blind, phase 3, randomised controlled trial.The lancet Diabetes & endocrinology. 2016 Dec 1;.41210041016
    [Google Scholar]
  115. (a HuangL. HuR. ZouH. Relative efficacy of five SGLT2 inhibitors: a network meta-analysis of 20 cardiovascular and respiratory outcomes.Front. Pharmacol.202415141972910.3389/fphar.2024.141972938933668
    [Google Scholar]
  116. (b CosentinoF. CannonC.P. CherneyD.Z. MasiukiewiczU. PratleyR. Dagogo-JackS. FrederichR. CharbonnelB. MancusoJ. ShihW.J. TerraS.G. Efficacy of ertugliflozin on heart failure–related events in patients with type 2 diabetes mellitus and established atherosclerotic cardiovascular disease: results of the VERTIS CV Trial.Circulation2020 Dec 8 1422322052215
    [Google Scholar]
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