Advertisement

Comparison of the effects of 10 GLP-1 RA and SGLT2 inhibitor interventions on cardiovascular, mortality, and kidney outcomes in type 2 diabetes: A network meta-analysis of large randomized trials

Published:September 07, 2020DOI:https://doi.org/10.1016/j.pcd.2020.08.017

      Highlights

      • The relative benefit of new antidiabetic drugs for cardiorenal endpoints is unclear.
      • The most efficacious drugs vary with different cardiorenal endpoints.
      • Subcutaneous semaglutide and albiglutide are most effective for cardiac events.
      • Canagliflozin and empagliflozin are most effective for heart failure hospitalization.
      • Dapagliflozin and empagliflozin are most effective for kidney function progression.

      Abstract

      The relative efficacy of different sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in reducing cardiorenal events in type 2 diabetic adults is unclear. We searched PubMed and Embase. Three primary endpoints were major adverse cardiovascular events (MACE), hospitalization for heart failure (HHF), and kidney function progression (KFP). Bayesian network meta-analysis was conducted to synthesize hazard ratio (HR) and 95% confidence interval (CI). We calculated surface under the cumulative ranking curve (SUCRA) to rank drug treatments. Subcutaneous semaglutide (HR 0.73, 95% CI 0.55−0.96) and albiglutide (HR 0.76, 95% CI 0.63−0.93) significantly reduced MACE versus lixisenatide. Canagliflozin (HRs: 0.69, 0.68, 0.67 and 0.58) and empagliflozin (HRs: 0.70, 0.69, 0.68 and 0.59) significantly reduced HHF versus dulaglutide, exenatide, lixisenatide and subcutaneous semaglutide. Dapagliflozin (HRs: 0.62, 0.60, 0.68 and 0.63) and empagliflozin (HRs: 0.64, 0.61, 0.69 and 0.64) significantly reduced KFP versus dulaglutide, exenatide, liraglutide and lixisenatide. Different drug treatments had the maximum SUCRA values as for preventing different cardiorenal endpoints. Different GLP-1 RAs and SGLT2 inhibitors have different efficacy in preventing cardiorenal endpoints in type 2 diabetes, and the most efficacious drugs are different as for preventing different cardiorenal endpoints.

      Abbreviations:

      GLP-1 RAs (glucagon-like peptide 1 receptor agonists), SGLT2 inhibitors (sodium glucose cotransporter 2 inhibitors), MACE (major adverse cardiovascular events), HHF (hospitalization for heart failure), KFP (kidney function progression), CVD (cardiovascular death), MI (myocardial infarction), ACD (all-cause death), HR (hazard ratio), CI (confidence interval), RCT (randomized controlled trial), SUCRA (surface under the cumulative ranking curve)

      Keywords

      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 Primary Care Diabetes
      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.
        • et al.
        Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes.
        N. Engl. J. Med. 2015; 373: 2117-2128
        • Neal B.
        • Perkovic V.
        • Mahaffey K.W.
        • et al.
        Canagliflozin and cardiovascular and renal events in type 2 diabetes.
        N. Engl. J. Med. 2017; 377: 644-657
        • Wiviott S.D.
        • Raz I.
        • Bonaca M.P.
        • et al.
        Dapagliflozin and cardiovascular outcomes in type 2 diabetes.
        N. Engl. J. Med. 2019; 380: 347-357
        • Mahaffey K.W.
        • Jardine M.J.
        • Bompoint S.
        • 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
        • Pfeffer M.A.
        • Claggett B.
        • Diaz R.
        • et al.
        Lixisenatide in patients with type 2 diabetes and acute coronary syndrome.
        N. Engl. J. Med. 2015; 373: 2247-2257
        • Marso S.P.
        • Daniels G.H.
        • Brown-Frandsen K.
        • et al.
        Liraglutide and cardiovascular outcomes in type 2 diabetes.
        N. Engl. J. Med. 2016; 375: 311-322
        • Marso S.P.
        • Bain S.C.
        • Consoli A.
        • et al.
        Semaglutide and cardiovascular outcomes in patients with type 2 diabetes.
        N. Engl. J. Med. 2016; 375: 1834-1844
        • Holman R.R.
        • Bethel M.A.
        • Mentz R.J.
        • et al.
        Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes.
        N. Engl. J. Med. 2017; 377: 1228-1239
        • Hernandez A.F.
        • Green J.B.
        • Janmohamed S.
        • et al.
        Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (harmony outcomes): a double-blind, randomised placebo-controlled trial.
        Lancet. 2018; 392: 1519-1529
        • Gerstein H.C.
        • Colhoun H.M.
        • Dagenais G.R.
        • et al.
        Dulaglutide and cardiovascular outcomes in type 2 diabetes (rewind): a double-blind, randomised placebo-controlled trial.
        Lancet. 2019; 394: 121-130
        • Husain M.
        • Birkenfeld A.L.
        • Donsmark M.
        • et al.
        Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes.
        N. Engl. J. Med. 2019; 381: 841-851
        • Wanner C.
        • Inzucchi S.E.
        • Lachin J.M.
        • et al.
        Empagliflozin and progression of kidney disease in type 2 diabetes.
        N. Engl. J. Med. 2016; 375: 323-334
        • Perkovic V.
        • de Zeeuw D.
        • Mahaffey K.W.
        • et al.
        Canagliflozin and renal outcomes in type 2 diabetes: results from the canvas program randomised clinical trials.
        Lancet Diabetes Endocrinol. 2018; 6: 691-704
        • Mosenzon O.
        • Wiviott S.D.
        • Cahn A.
        • 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
        • Perkovic V.
        • Jardine M.J.
        • Neal B.
        • et al.
        Canagliflozin and renal outcomes in type 2 diabetes and nephropathy.
        N. Engl. J. Med. 2019; 380: 2295-2306
        • Gerstein H.C.
        • Colhoun H.M.
        • Dagenais G.R.
        • 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
        • Mann J.
        • Ørsted D.D.
        • Brown-Frandsen K.
        • et al.
        Liraglutide and renal outcomes in type 2 diabetes.
        N. Engl. J. Med. 2017; 377: 839-848
        • Zelniker T.A.
        • Wiviott S.D.
        • Raz I.
        • 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
        • Kristensen S.L.
        • Rorth R.
        • Jhund P.S.
        • et al.
        Cardiovascular, mortality, and kidney outcomes with glp-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials.
        Lancet Diabetes Endocrinol. 2019; 7: 776-785
        • Fei Y.
        • Tsoi M.F.
        • Cheung B.
        Cardiovascular outcomes in trials of new antidiabetic drug classes: a network meta-analysis.
        Cardiovasc. Diabetol. 2019; 18: 112
        • Hussein H.
        • Zaccardi F.
        • Khunti K.
        • Seidu S.
        • Davies M.J.
        • Gray L.J.
        Cardiovascular efficacy and safety of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists: a systematic review and network meta-analysis.
        Diabet. Med. 2019; 36: 444-452
        • Buse J.B.
        • Wexler D.J.
        • Tsapas A.
        • et al.
        2019 update to: management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American diabetes association (ADA) and the European association for the study of diabetes (EASD).
        Diabetes Care. 2020; 43: 487-493
        • Giugliano D.
        • Esposito K.
        Class effect for sglt-2 inhibitors: a tale of 9 drugs.
        Cardiovasc. Diabetol. 2019; 18: 94
        • Giugliano D.
        • Meier J.J.
        • Esposito K.
        Heart failure and type 2 diabetes: from cardiovascular outcome trials, with hope.
        Diabetes Obes. Metab. 2019; 21: 1081-1087