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Comparison of effects of SGLT-2 inhibitors and GLP-1 receptor agonists on cardiovascular and renal outcomes in type 2 diabetes mellitus patients with/without albuminuria: A systematic review and network meta-analysis

  • Author Footnotes
    1 These authors contributed equally to this work.
    Yuki Kawai
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan
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  • Author Footnotes
    1 These authors contributed equally to this work.
    Kazushi Uneda
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan

    Department of Kampo Medicine, Aizu Medical Center, Fukushima Medical University School of Medicine, 21-2 Maeda, Tanisawa, Kawahigashi, Aizuwakamatsu 969-3492, Japan
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  • Takayuki Yamada
    Affiliations
    Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan

    Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
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  • Sho Kinguchi
    Correspondence
    Corresponding authorsat: Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
    Affiliations
    Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan
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  • Kazuo Kobayashi
    Affiliations
    Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan

    Committee of Hypertension and Kidney Disease, Kanagawa Physicians Association, Yokohama, Japan
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  • Kengo Azushima
    Affiliations
    Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan
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  • Tomohiko Kanaoka
    Affiliations
    Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan
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  • Yoshiyuki Toya
    Affiliations
    Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan
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  • Hiromichi Wakui
    Correspondence
    Corresponding authorsat: Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
    Affiliations
    Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan
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  • Kouichi Tamura
    Affiliations
    Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan
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  • Author Footnotes
    1 These authors contributed equally to this work.
Published:November 12, 2021DOI:https://doi.org/10.1016/j.diabres.2021.109146

      Abstract

      Aims

      It remains unclear which sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are most effective for preventing cardiovascular and renal events in type 2 diabetes mellitus (T2DM) patients, depending on the presence of albuminuria. We conducted a network meta-analysis to compare the efficacy of these two drug classes in T2DM patients with/without albuminuria.

      Methods

      We searched the Medline, EMBASE, Cochrane Library databases, and gray literature up to April 20, 2021. We included randomized controlled trials that reported the risk of major adverse cardiovascular events (MACE) and composite of renal outcomes in T2DM.

      Results

      A total of nine studies (81,206 patients) were included. In patients with/without albuminuria, SGLT-2 inhibitors did not significantly reduce the risk of MACE compared with GLP-1 RAs (risk ratio [RR] [95% confidence interval]; 0.96 [0.82–1.12] and 0.94 [0.81–1.10], respectively). In contrast, compared with GLP-1 RAs, SGLT-2 inhibitors were associated with significantly lower renal risk in both patients with/without albuminuria (RR [95% CI]; 0.75 [0.63–0.89] and 0.59 [0.44–0.79], respectively).

      Conclusions

      SGLT-2 inhibitors may be superior to GLP-1 RAs for renal outcomes in T2DM patients with/without albuminuria, although there was no difference in the risk of MACE.

      Keywords

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      References

        • Saeedi P.
        • Petersohn I.
        • Salpea P.
        • Malanda B.
        • Karuranga S.
        • Unwin N.
        • et al.
        Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9(th) edition.
        Diabetes Res Clin Pract. 2019; 157: 107843https://doi.org/10.1016/j.diabres.2019.107843
        • Moss S.E.
        • Klein R.
        • Klein B.E.
        Cause-specific mortality in a population-based study of diabetes.
        Am J Public Health. 1991; 81: 1158-1162
        • Tuttle K.R.
        • Stein J.H.
        • DeFronzo R.A.
        The natural history of diabetic nephropathy.
        Semin Nephrol. 1990; 10: 184-193
        • Ogurtsova K.
        • da Rocha Fernandes J.D.
        • Huang Y.
        • Linnenkamp U.
        • Guariguata L.
        • Cho N.H.
        • et al.
        IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040.
        Diabetes Res Clin Pract. 2017; 128: 40-50
        • Liyanage T.
        • Ninomiya T.
        • Jha V.
        • Neal B.
        • Patrice H.M.
        • Okpechi I.
        • et al.
        Worldwide access to treatment for end-stage kidney disease: a systematic review.
        Lancet. 2015; 385: 1975-1982
        • Einarson T.R.
        • Acs A.
        • Ludwig C.
        • Panton U.H.
        Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007–2017.
        Cardiovasc Diabetol. 2018; 17: 83
        • 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
        • 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
        • Marso S.P.
        • Daniels G.H.
        • Brown-Frandsen K.
        • Kristensen P.
        • Mann J.F.
        • Nauck M.A.
        • et al.
        Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes.
        N Engl J Med. 2016; 375: 311-322
        • Gerstein H.C.
        • Colhoun H.M.
        • Dagenais G.R.
        • Diaz R.
        • Lakshmanan M.
        • Pais P.
        • et al.
        Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial.
        Lancet. 2019; 394: 131-138
        • American D.A.
        9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2021.
        Diabetes Care. 2021; 44: S111-S124
        • Palmer S.C.
        • Tendal B.
        • Mustafa R.A.
        • Vandvik P.O.
        • Li S.
        • Hao Q.
        • et al.
        Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials.
        BMJ. 2021; 372m4573
        • Qiu M.
        • Ding L.L.
        • Wei X.B.
        • Liu S.Y.
        • Zhou H.R.
        Comparative Efficacy of Glucagon-like Peptide 1 Receptor Agonists and Sodium Glucose Cotransporter 2 Inhibitors for Prevention of Major Adverse Cardiovascular Events in Type 2 Diabetes: A Network Meta-analysis.
        J Cardiovasc Pharmacol. 2021; 77: 34-37
        • Yamada T.
        • Wakabayashi M.
        • Bhalla A.
        • Chopra N.
        • Miyashita H.
        • Mikami T.
        • et al.
        Cardiovascular and renal outcomes with SGLT-2 inhibitors versus GLP-1 receptor agonists in patients with type 2 diabetes mellitus and chronic kidney disease: a systematic review and network meta-analysis.
        Cardiovasc Diabetol. 2021; 20: 14
        • Jager A.
        • Kostense P.J.
        • Ruhe H.G.
        • Heine R.J.
        • Nijpels G.
        • Dekker J.M.
        • et al.
        Microalbuminuria and peripheral arterial disease are independent predictors of cardiovascular and all-cause mortality, especially among hypertensive subjects: five-year follow-up of the Hoorn Study.
        Arterioscler Thromb Vasc Biol. 1999; 19: 617-624
        • Persson F.
        • Rossing P.
        Diagnosis of diabetic kidney disease: state of the art and future perspective.
        Kidney Int Suppl. 2011; 2018: 2-7
        • Araki S.
        • Haneda M.
        • Koya D.
        • Hidaka H.
        • Sugimoto T.
        • Isono M.
        • et al.
        Reduction in microalbuminuria as an integrated indicator for renal and cardiovascular risk reduction in patients with type 2 diabetes.
        Diabetes. 2007; 56: 1727-1730
      1. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535.

        • Hutton B.
        • Salanti G.
        • Caldwell D.M.
        • Chaimani A.
        • Schmid C.H.
        • Cameron C.
        • et al.
        The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations.
        Ann Intern Med. 2015; 162: 777-784
        • Viera A.J.
        • Garrett J.M.
        Understanding interobserver agreement: the kappa statistic.
        Fam Med. 2005; 37: 360-363
        • Higgins J.P.
        • Altman D.G.
        • Gotzsche P.C.
        • Juni P.
        • Moher D.
        • Oxman A.D.
        • et al.
        The Cochrane Collaboration's tool for assessing risk of bias in randomised trials.
        BMJ. 2011; 343d5928
        • Casadei-Gardini A.
        • Vagheggini A.
        • Gelsomino F.
        • Spallanzani A.
        • Ulivi P.
        • Orsi G.
        • et al.
        Is There an Optimal Choice in Refractory Colorectal Cancer? A Network Meta-Analysis.
        Clin Colorectal Cancer. 2020; 19e9
        • Pula A.
        • Stawiski K.
        • Braun M.
        • Iskierka-Jazdzewska E.
        • Robak T.
        Efficacy and safety of B-cell receptor signaling pathway inhibitors in relapsed/refractory chronic lymphocytic leukemia: a systematic review and meta-analysis of randomized clinical trials.
        Leuk Lymphoma. 2018; 59: 1084-1094
        • Higgins J.P.
        • Thompson S.G.
        • Deeks J.J.
        • Altman D.G.
        Measuring inconsistency in meta-analyses.
        BMJ. 2003; 327: 557-560
        • Higgins J.P.
        • Thompson S.G.
        Quantifying heterogeneity in a meta-analysis.
        Stat Med. 2002; 21: 1539-1558
        • Egger M.
        • Davey Smith G.
        • Schneider M.
        • Minder C.
        Bias in meta-analysis detected by a simple, graphical test.
        BMJ. 1997; 315: 629-634
        • 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
        • Mosenzon O.
        • Wiviott S.D.
        • Cahn A.
        • Rozenberg A.
        • Yanuv I.
        • Goodrich E.L.
        • et al.
        Effects of dapagliflozin on development and progression of kidney disease in patients with type 2 diabetes: an analysis from the DECLARE-TIMI 58 randomised trial.
        Lancet Diabetes Endocrinol. 2019; 7: 606-617
        • Cherney D.Z.I.
        • McGuire D.K.
        • Charbonnel B.
        • Cosentino F.
        • Pratley R.
        • Dagogo-Jack S.
        • et al.
        Gradient of Risk and Associations With Cardiovascular Efficacy of Ertugliflozin by Measures of Kidney Function: Observations From VERTIS CV.
        Circulation. 2021; 143: 602-605
        • Bhatt D.L.
        • Szarek M.
        • Pitt B.
        • Cannon C.P.
        • Leiter L.A.
        • McGuire D.K.
        • et al.
        Sotagliflozin in Patients with Diabetes and Chronic Kidney Disease.
        N Engl J Med. 2021; 384: 129-139
        • Pfeffer M.A.
        • Claggett B.
        • Diaz R.
        • Dickstein K.
        • Gerstein H.C.
        • Kober L.V.
        • et al.
        Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome.
        N Engl J Med. 2015; 373: 2247-2257
        • Mann J.F.E.
        • Orsted D.D.
        • Brown-Frandsen K.
        • Marso S.P.
        • Poulter N.R.
        • Rasmussen S.
        • et al.
        Liraglutide and Renal Outcomes in Type 2 Diabetes.
        N Engl J Med. 2017; 377: 839-848
        • Muskiet M.H.A.
        • Tonneijck L.
        • Huang Y.
        • Liu M.
        • Saremi A.
        • Heerspink H.J.L.
        • et al.
        Lixisenatide and renal outcomes in patients with type 2 diabetes and acute coronary syndrome: an exploratory analysis of the ELIXA randomised, placebo-controlled trial.
        Lancet Diabetes Endocrinol. 2018; 6: 859-869
        • Neuen B.L.
        • Ohkuma T.
        • Neal B.
        • Matthews D.R.
        • de Zeeuw D.
        • Mahaffey K.W.
        • et al.
        Effect of Canagliflozin on Renal and Cardiovascular Outcomes across Different Levels of Albuminuria: Data from the CANVAS Program.
        J Am Soc Nephrol. 2019; 30: 2229-2242
        • Wanner C.
        • Inzucchi S.E.
        • Lachin J.M.
        • Fitchett D.
        • von Eynatten M.
        • Mattheus M.
        • et al.
        Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes.
        N Engl J Med. 2016; 375: 323-334
        • Mann J.F.E.
        • Fonseca V.
        • Mosenzon O.
        • Raz I.
        • Goldman B.
        • Idorn T.
        • et al.
        Effects of Liraglutide Versus Placebo on Cardiovascular Events in Patients With Type 2 Diabetes Mellitus and Chronic Kidney Disease.
        Circulation. 2018; 138: 2908-2918
        • Zelniker T.A.
        • Wiviott S.D.
        • Raz I.
        • Im K.
        • Goodrich E.L.
        • Furtado R.H.M.
        • et al.
        Comparison of the Effects of Glucagon-Like Peptide Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors for Prevention of Major Adverse Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus.
        Circulation. 2019; 139: 2022-2031
        • Kim M.
        • Platt M.J.
        • Shibasaki T.
        • Quaggin S.E.
        • Backx P.H.
        • Seino S.
        • et al.
        GLP-1 receptor activation and Epac2 link atrial natriuretic peptide secretion to control of blood pressure.
        Nat Med. 2013; 19: 567-575
        • Sattar N.
        • McLaren J.
        • Kristensen S.L.
        • Preiss D.
        • McMurray J.J.
        SGLT2 Inhibition and cardiovascular events: why did EMPA-REG Outcomes surprise and what were the likely mechanisms?.
        Diabetologia. 2016; 59: 1333-1339
        • Cherney D.Z.
        • Perkins B.A.
        • Soleymanlou N.
        • Maione M.
        • Lai V.
        • Lee A.
        • et al.
        Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus.
        Circulation. 2014; 129: 587-597
        • Tanaka T.
        • Higashijima Y.
        • Wada T.
        • Nangaku M.
        The potential for renoprotection with incretin-based drugs.
        Kidney Int. 2014; 86: 701-711
        • Korner A.
        • Eklof A.C.
        • Celsi G.
        • Aperia A.
        Increased renal metabolism in diabetes.
        Mechanism and functional implications. Diabetes. 1994; 43: 629-633
        • Sano M.
        • Takei M.
        • Shiraishi Y.
        • Suzuki Y.
        Increased Hematocrit During Sodium-Glucose Cotransporter 2 Inhibitor Therapy Indicates Recovery of Tubulointerstitial Function in Diabetic Kidneys.
        J Clin Med Res. 2016; 8: 844-847
        • Mudaliar S.
        • Alloju S.
        • Henry R.R.
        Can a Shift in Fuel Energetics Explain the Beneficial Cardiorenal Outcomes in the EMPA-REG OUTCOME Study?.
        A Unifying Hypothesis. Diabetes Care. 2016; 39: 1115-1122
        • Mahaffey K.W.
        • Jardine M.J.
        • Bompoint S.
        • Cannon C.P.
        • Neal B.
        • Heerspink H.J.L.
        • et al.
        Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups.
        Circulation. 2019; 140: 739-750
        • Rangaswami J.
        • Bhalla V.
        • de Boer I.H.
        • Staruschenko A.
        • Sharp J.A.
        • Singh R.R.
        • et al.
        Cardiorenal Protection With the Newer Antidiabetic Agents in Patients With Diabetes and Chronic Kidney Disease: A Scientific Statement From the American Heart Association.
        Circulation. 2020; 142: e265-e286
        • Zhu J.
        • Yu X.
        • Zheng Y.
        • Li J.
        • Wang Y.
        • Lin Y.
        • et al.
        Association of glucose-lowering medications with cardiovascular outcomes: an umbrella review and evidence map.
        Lancet Diabetes Endocrinol. 2020; 8: 192-205
        • Arakawa M.
        • Mita T.
        • Azuma K.
        • Ebato C.
        • Goto H.
        • Nomiyama T.
        • et al.
        Inhibition of monocyte adhesion to endothelial cells and attenuation of atherosclerotic lesion by a glucagon-like peptide-1 receptor agonist, exendin-4.
        Diabetes. 2010; 59: 1030-1037
        • Bruen R.
        • Curley S.
        • Kajani S.
        • Crean D.
        • O'Reilly M.E.
        • Lucitt M.B.
        • et al.
        Liraglutide dictates macrophage phenotype in apolipoprotein E null mice during early atherosclerosis.
        Cardiovasc Diabetol. 2017; 16: 143
        • 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
        • Neuen B.L.
        • Young T.
        • Heerspink H.J.L.
        • Neal B.
        • Perkovic V.
        • Billot L.
        • et al.
        SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis.
        Lancet Diabetes Endocrinol. 2019; 7: 845-854
        • Wheeler D.C.
        • Stefansson B.V.
        • Jongs N.
        • Chertow G.M.
        • Greene T.
        • Hou F.F.
        • et al.
        Effects of dapagliflozin on major adverse kidney and cardiovascular events in patients with diabetic and non-diabetic chronic kidney disease: a prespecified analysis from the DAPA-CKD trial.
        Lancet Diabetes Endocrinol. 2021; 9: 22-31