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Cardiovascular outcome studies in type 2 diabetes: Comparison between SGLT2 inhibitors and GLP-1 receptor agonists

  • André J. Scheen
    Correspondence
    Address: Department of Medicine, CHU Sart Tilman (B35), B-4000 LIEGE 1, Belgium.
    Affiliations
    Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU Liège, University of Liège, Liège, Belgium
    Clinical Pharmacology Unit, CHU Liège, Center for Interdisciplinary Research on Medicines (CIRM), University of Liège, Liège, Belgium
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      Highlights

      • Both SGLT2is and GLP-1RAs have proven cardiovascular protection.
      • Preferably empagliflozin or liraglutide in patients with cardiovascular disease.
      • Preferably a SGLT2i in patients with or at risk of heart failure.
      • Preferably a GLP-1RA in patients with moderate to severe kidney disease.
      • Potential combined therapy if complementary cardiorenal protective mechanisms.

      Abstract

      Sodium-glucose cotransporter type 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are two pharmacological classes that have proven their efficacy to reduce major cardiovascular events (MACEs) in patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease in large prospective cardiovascular outcome trials (CVOTs): EMPA-REG OUTCOME (empagliflozin), CANVAS (canagliflozin), LEADER (liraglutide) and SUSTAIN 6 (semaglutide). Some heterogeneity appears to exist between the various agents within the two pharmacological classes. Whether these positive results could be extrapolated to patients without cardiovascular disease is still unknown. The underlying mechanisms remain a matter of debate but appear to differ between SGLT2is and GLP-1RAs. One crucial question is which patient’s characteristics should be taken into account to guide the choice between a SGLT2i or a GLP-1RA according to a personalized approach. Heart failure should encourage the use of a SGLT2i whereas moderate to severe chronic kidney disease should favour the prescription of a GLP-1RA. Despite the results of recent CVOTs, numerous patients who are good candidates for benefiting of these agents do not receive them in clinical practice. Currently, there is a paradigm shift in T2DM management, moving from a primary objective of glucose control to a cardiovascular and renal protection.

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