Advertisement

SGLT2 inhibitors: Do we need other evidences?

Published:April 06, 2021DOI:https://doi.org/10.1016/j.ejim.2021.03.027
      The five cardiovascular outcome trials (CVOT) conducted in patients with type 2 diabetes mellitus so far have shown that renal sodium-glucose cotransporters two inhibitors (SGLT2i) are cardiovascular (CV) safe [
      • Zinman B.
      • Wanner C.
      • Lachin J.M.
      • Fitchett D.
      • Bluhmki E.
      • Hantel S.
      • et al.
      Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes.
      ,
      • Wiviott S.D.
      • Raz I.
      • Bonaca M.P.
      • Mosenzon O.
      • Kato E.T.
      • Cahn A.
      • et al.
      Dapagliflozin and cardiovascular outcomes in type 2 diabetes.
      ,
      • Neal B.
      • Perkovic V.
      • Mahaffey K.W.
      • de Zeeuw D.
      • Fulcher G.
      • Erondu N.
      • et al.
      Canagliflozin and cardiovascular and renal events in type 2 diabetes.
      ,
      • Perkovic V.
      • Jardine M.J.
      • Neal B.
      • Bompoint S.
      • Heerspink H.J.L.
      • Charytan D.M.
      • et al.
      Canagliflozin and renal outcomes in type 2 diabetes and nephropathy.
      ,
      • Cannon C.P.
      • Pratley R.
      • Dagogo-Jack S.
      • Mancuso J.
      • Huyck S.
      • Masiukiewicz U.
      • et al.
      Cardiovascular outcomes with ertugliflozin in type 2 diabetes.
      ]. This finding paved the way for their use in patients with type 2, and even type 1, diabetes to reduce the HbA1c by 0.5 to 1.5%, depending on the baseline values. However, CVOT demonstrated a CV benefits of SGLT2i well beyond their antidiabetic effect.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to European Journal of Internal Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Zinman B.
        • Wanner C.
        • Lachin J.M.
        • Fitchett D.
        • Bluhmki E.
        • Hantel S.
        • et al.
        Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes.
        N Engl J Med. 2015; 373: 2117-2128
        • Wiviott S.D.
        • Raz I.
        • Bonaca M.P.
        • Mosenzon O.
        • Kato E.T.
        • Cahn A.
        • et al.
        Dapagliflozin and cardiovascular outcomes in type 2 diabetes.
        N Engl J Med. 2019; 380: 347-357
        • Neal B.
        • Perkovic V.
        • Mahaffey K.W.
        • de Zeeuw D.
        • Fulcher G.
        • Erondu N.
        • et al.
        Canagliflozin and cardiovascular and renal events in type 2 diabetes.
        N Engl J Med. 2017; 377: 644-657
        • Perkovic V.
        • Jardine M.J.
        • Neal B.
        • Bompoint S.
        • Heerspink H.J.L.
        • Charytan D.M.
        • et al.
        Canagliflozin and renal outcomes in type 2 diabetes and nephropathy.
        N Engl J Med. 2019; 380: 2295-2306
        • Cannon C.P.
        • Pratley R.
        • Dagogo-Jack S.
        • Mancuso J.
        • Huyck S.
        • Masiukiewicz U.
        • et al.
        Cardiovascular outcomes with ertugliflozin in type 2 diabetes.
        N Engl J Med. 2020; 383: 1425-1435
        • Zelniker T.A.
        • Wiviott S.D.
        • Raz I.
        • Im K.
        • Goodrich E.L.
        • Bonaca M.P.
        • 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: 31-39
        • McGuire D.K.
        • Shih W.J.
        • Cosentino F.
        • Charbonnel B.
        • Cherney D.Z.I.
        • Dagogo-Jack S.
        • et al.
        Association of SGLT2 inhibitors with cardiovascular and kidney outcomes in patients with type 2 diabetes: a meta-analysis.
        JAMA Cardiol. 2021; 6: 148-158
        • McMurray J.J.V.
        • Solomon S.D.
        • Inzucchi S.E.
        • Kober L.
        • Kosiborod M.N.
        • Martinez F.A.
        • et al.
        Dapagliflozin in patients with heart failure and reduced ejection fraction.
        N Engl J Med. 2019; 381: 1995-2008
        • Packer M.
        • Anker S.D.
        • Butler J.
        • Filippatos G.
        • Pocock S.J.
        • Carson P.
        • et al.
        Cardiovascular and renal outcomes with empagliflozin in heart failure.
        N Engl J Med. 2020; 383: 1413-1424
        • Heerspink H.J.L.
        • Stefansson B.V.
        • Correa-Rotter R.
        • Chertow G.M.
        • Greene T.
        • Hou F.F.
        • et al.
        Dapagliflozin in patients with chronic kidney disease.
        N Engl J Med. 2020; 383: 1436-1446
        • Packer M.
        • Anker S.D.
        • Butler J.
        • Filippatos G.
        • Ferreira J.P.
        • Pocock S.J.
        • et al.
        Influence of neprilysin inhibition on the efficacy and safety of empagliflozin in patients with chronic heart failure and a reduced ejection fraction: the EMPEROR-reduced trial.
        Eur Heart J. 2021; 42: 671-680
        • Scheen A.J.
        Sodium-glucose cotransporter type 2 inhibitors for the treatment of type 2 diabetes mellitus.
        Nat Rev Endocrinol. 2020; 16: 556-577
        • Yuan Lu F.L.
        • Fan Y.
        • Yang Yu
        • Chen M.
        • Xi J.
        Effect of SGLT-2 inhibitors on cardiovascular outcomesvin heart failure patients: a meta-analysis of randomized controlled trials.
        Eur J Intern Med. 2021; ([TO PRODUCTION: PLEASE UPDATE WITH DOI])
        • Bhatt D.L.
        • Szarek M.
        • Steg P.G.
        • Cannon C.P.
        • Leiter L.A.
        • McGuire D.K.
        • et al.
        Sotagliflozin in patients with diabetes and recent worsening heart failure.
        N Engl J Med. 2021; 384: 117-128
        • Cosentino F.
        • Grant P.J.
        • Aboyans V.
        • Bailey C.J.
        • Ceriello A.
        • Delgado V.
        • et al.
        2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD.
        Eur Heart J. 2020; 41: 255-323
        • Avogaro A.
        • Fadini G.P.
        • Del Prato S.
        Reinterpreting cardiorenal protection of renal sodium-glucose cotransporter 2 inhibitors via cellular life history programming.
        Diabetes Care. 2020; 43: 501-507
        • Baartscheer A.
        • Schumacher C.A.
        • Wust R.C.
        • Fiolet J.W.
        • Stienen G.J.
        • Coronel R.
        • et al.
        Empagliflozin decreases myocardial cytoplasmic Na(+) through inhibition of the cardiac Na(+)/H(+) exchanger in rats and rabbits.
        Diabetologia. 2017; 60: 568-573
        • Griffin M.
        • Rao V.S.
        • Ivey-Miranda J.
        • Fleming J.
        • Mahoney D.
        • Maulion C.
        • et al.
        Empagliflozin in heart failure: diuretic and cardiorenal effects.
        Circulation. 2020; 142: 1028-1039
        • Onishi A.
        • Fu Y.
        • Patel R.
        • Darshi M.
        • Crespo-Masip M.
        • Huang W.
        • et al.
        A role for tubular Na(+)/H(+) exchanger NHE3 in the natriuretic effect of the SGLT2 inhibitor empagliflozin.
        Am J Physiol Renal Physiol. 2020; 319: F712-F728
        • Damman K.
        • Beusekamp J.C.
        • Boorsma E.M.
        • Swart H.P.
        • Smilde T.D.J.
        • Elvan A.
        • et al.
        Randomized, double-blind, placebo-controlled, multicentre pilot study on the effects of empagliflozin on clinical outcomes in patients with acute decompensated heart failure (EMPA-RESPONSE-AHF).
        Eur J Heart Fail. 2020; 22: 713-722
        • McMurray J.J.V.
        • Packer M.
        How should we sequence the treatments for heart failure and a reduced ejection fraction?: A redefinition of evidence-based medicine.
        Circulation. 2021; 143: 875-877
        • Sacco S.
        • Marini C.
        • Olivieri L.
        • Pistoia F.
        • Carolei A.
        Contribution of hematocrit to early mortality after ischemic stroke.
        Eur Neurol. 2007; 58: 233-238
        • Fadini G.P.
        • Avogaro A.
        SGLT2 inhibitors and amputations in the US FDA adverse event reporting system.
        Lancet Diabetes Endocrinol. 2017; 5: 680-681
        • Fadini G.P.
        • Zatti G.
        • Baldi I.
        • Bottigliengo D.
        • Consoli A.
        • Giaccari A.
        • et al.
        Use and effectiveness of dapagliflozin in routine clinical practice: an Italian multicentre retrospective study.
        Diabetes Obes Metab. 2018; 20: 1781-1786

      Linked Article