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Canadian Journal of Cardiology

Obvious Differences Between GLP1RAs and SGLT2is in the Outcomes of Heart Failure, Renal Failure, and Stroke

Published:August 22, 2022DOI:https://doi.org/10.1016/j.cjca.2022.08.223
      Ali et al.
      • Ali M.U.
      • Mancini G.
      • Fitzpatrick-Lewis D.
      • et al.
      The effectiveness of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists on cardiorenal outcomes: systematic review and meta-analysis.
      conducted a wonderful and comprehensive meta-analysis
      • Ali M.U.
      • Mancini G.
      • Fitzpatrick-Lewis D.
      • et al.
      The effectiveness of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists on cardiorenal outcomes: systematic review and meta-analysis.
      based on all the available cardiovascular outcome trials (CVOTs) of sodium-glucose cotransporter 2 inhibitors (SGLT2is; 11 CVOTs) and glucagon-like peptide 1 receptor agonists (GLP1RAs; 8 CVOTs), drawing their main conclusion that both SGLT2is and GLP1RAs yielded the statistically significant benefits across most cardiorenal end points in the populations studied. This conclusion only emphasises the similarity between GLP1RAs and SGLT2is in cardiorenal benefits, but ignores the differences between them in specific cardiorenal outcomes. As shown in Supplemental Figure S5A in Ali et al.’s article, compared with placebo, SGLT2is reduced heart failure hospitalisation (HFH) by 31% while GLP1RAs reduced HFH by 9% (P for subgroup difference [Psubgroup] < 0.01). SGLT2is reduced kidney composite outcome (KCO) by 36% while GLP1RAs reduced KCO by 22% (Psubgroup = 0.04) (Supplemental Fig. S9A). Moreover, GLP1RAs reduced nonfatal stroke by 16% while SGLT2is had no significant effects on nonfatal stroke (Psubgroup = 0.04) (Supplemental Fig. S7A). These results suggest the obvious superiority of SGLT2is over GLP1RAs in lowering heart failure (HF) and renal failure outcomes and that of GLP1RAs over SGLT2is in lowering stroke. Two network meta-analyses
      • Giugliano D.
      • Longo M.
      • Signoriello S.
      • et al.
      The effect of DPP-4 inhibitors, GLP-1 receptor agonists and SGLT-2 inhibitors on cardiorenal outcomes: a network meta-analysis of 23 CVOTs.
      ,
      • Lin D.S.
      • Lee J.K.
      • Hung C.S.
      • Chen W.J.
      The efficacy and safety of novel classes of glucose-lowering drugs for cardiovascular outcomes: a network meta-analysis of randomised clinical trials.
      based on CVOTs confirmed these findings. Therefore, the authors should mention, in their Conclusion, these differences between GLP1RAs and SGLT2is for better guiding of clinical practice.
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      References

        • Ali M.U.
        • Mancini G.
        • Fitzpatrick-Lewis D.
        • et al.
        The effectiveness of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists on cardiorenal outcomes: systematic review and meta-analysis.
        Can J Cardiol. 2022; 38: 1201-1210
        • Giugliano D.
        • Longo M.
        • Signoriello S.
        • et al.
        The effect of DPP-4 inhibitors, GLP-1 receptor agonists and SGLT-2 inhibitors on cardiorenal outcomes: a network meta-analysis of 23 CVOTs.
        Cardiovasc Diabetol. 2022; 21: 42
        • Lin D.S.
        • Lee J.K.
        • Hung C.S.
        • Chen W.J.
        The efficacy and safety of novel classes of glucose-lowering drugs for cardiovascular outcomes: a network meta-analysis of randomised clinical trials.
        Diabetologia. 2021; 64: 2676-2686
        • Mancini G.
        • O’Meara E.
        • Zieroth S.
        • et al.
        2022 Canadian Cardiovascular Society guideline for use of GLP-1 receptor agonists and SGLT2 inhibitors for cardiorenal risk reduction in adults.
        Can J Cardiol. 2022; 38: 1153-1167

      Linked Article

      • Reply to Du et al.—Obvious Differences Between GLP1RAs and SGLT2is in the Outcomes of Heart Failure, Renal Failure, and Stroke
        Canadian Journal of Cardiology
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          Thank you, Dr Du, for the commentary1 regarding our article, “The Effectiveness of Sodium-Glucose Cotransporter 2 Inhibitors and Glucagon-like Peptide-1 Receptor Agonists on Cardiorenal Outcomes: Systematic Review and Meta-analysis.”2 The differential effectiveness of the 2 classes regarding the aforementioned critical end points was highlighted in the review’s results and discussion sections. In addition, distinctions were made on a clinical basis in the guideline (published in parallel) and specifically concerning the absence of dedicated trials for GLP-1RAs in patients with heart failure or chronic kidney disease.
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