Effect of SGLT-2 inhibitors on cardiovascular outcomes in heart failure patients: A meta-analysis of randomized controlled trials

Published:April 03, 2021DOI:


      • SGLT-2i have remarkable cardioprotective effects in a broad range of HF patient.
      • Risk of CVD/HHF in HF patients was significant decreased by 23% in SGLT-2i group.
      • Beneficial effects were robust and unchanged when stratified by T2DM status.
      • Safety profiles were generally comparable between SGLT-2i and placebo groups.



      To investigate the overall effect of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) on cardiovascular outcomes in a broad spectrum of heart failure (HF) patients, and further stratified by status of ejection fraction and diabetes mellitus.


      Electronic databases were searched to identify randomized controlled trials that compared SGLT-2i with placebo in patients with HF. Efficacy outcomes included the composite of cardiovascular death (CVD) or hospitalization for heart failure (HHF), individual CVD, individual HHF, and all-cause mortality (ACM).


      A total of 8 large trials comprising 16,460 HF patients were enrolled. Pooled data demonstrated that SGLT-2i significantly reduced the risk for primary composite outcome (CVD or HHF) by 23% (HR: 0.77, 95% CI: 0.72–0.82) in HF patients. Use of SGLT-2i was associated with a statistically significant 32% reduction in HHF (HR: 0.68, 95% CI: 0.62–0.75), a 15% reduction in CVD (HR: 0.85, 95% CI: 0.76–0.94) and a 16% reduction in ACM (HR: 0.84, 95% CI: 0.77–0.92). Sensitivity analyses using Mantel-Haenszel method displayed consistent results. Subgroup analyses demonstrated that SGLT-2i were robustly effective in HFrEF subgroup as well as in HF with absence/presence of T2DM, and displayed a strong trend to be effective in HFpEF. Safety analysis demonstrated SGLT-2i group had a lower proportion of serious adverse events than placebo group (RR 0.89, 95% CI: 0.86–0.93).


      Compared with placebo, SGLT-2 inhibitors have remarkable cardiovascular benefits in a broad range of HF patients. Beneficial effects were robust in HF patients regardless of T2DM status, and a strong trend to be effective in HFpEF.


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      Linked Article

      • SGLT2 inhibitors: Do we need other evidences?
        European Journal of Internal MedicineVol. 87
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          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 [1–5]. 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.
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