Abstract
BackgroundIt has been suggested that sodium–glucose cotransporter 2 (SGLT-2) inhibitors reduce the cardiorenal risk in patients with type 2 diabetes (T2D). The purpose of this study is to provide an update of all large cardiovascular outcome trials (CVOTs) with SGLT-2 inhibitors to assess their cardiorenal efficacy in patients with and without T2D.MethodsAn electronic search up to 30 September 2021 was conducted in PubMed, EMBASE, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov. to determine eligible trials. We included CVOTs comparing any SGLT-2 inhibitor with placebo, reporting desired cardiovascular or renal outcomes and with a follow-up duration of at least 6 months.ResultsEleven CVOTs, with data from five SGLT-2 inhibitors (empagliflozin, canagliflozin, dapagliflozin, ertugliflozin and sotagliflozin) and 77,541 participants, were included. In the overall analysis, the risk of the composite CV mortality or hospitalization for heart failure (HF) was reduced by 23% (HR = 0.77, 95% CI 0.73–0.82, P < 0.001) compared with placebo, with not significant heterogeneity (I2 = 26%, P = 0.20), and irrespective of the presence of T2D (P for interaction = 0.81) and age (> 65 vs ≤ 65 years, P for interaction = 0.78). The risk of CV mortality, total mortality and hospitalization for HF was significantly reduced by 16%, 13%, and 32%, respectively; similarly, the risk of the composite renal outcome was reduced by 35% (HR = 0.65, 95% CI 0.56–0.75), with moderate heterogeneity (I2 = 32%). In the analysis of 6 CVOTs reporting the data, the risk of major cardiovascular events (MACE) was reduced by 12%, with low heterogeneity (I2 = 21.2%, P = 0.19) and irrespective of the presence of established CV disease at baseline (P for interaction = 0.46).ConclusionsTherapy with SGLT-2 inhibitors in patients with cardiometabolic and renal diseases results in a sustained to moderate reduction of the composite CV death or hospitalization for HF, robust reduction of HF and renal outcomes, moderate reduction of CV mortality, total mortality and MACE.
Highlights
Inhibitors of the sodium–glucose co-transporter 2 (SGLT-2) were initially developed for the treatment of type 2 diabetes (T2D) for their effect of lowering blood glucose levels through increased excretion of glucose in the urine [1]
One key question is how the effects of sodium–glucose cotransporter 2 (SGLT-2) inhibitors compared in patients with and without T2D, and whether the findings of the completed trials support the hypothesis that SGLT-2 inhibition might be an effective treatment for patients with heart failure, including those without diabetes
The aim of this meta-analysis was to provide an update of all large cardiovascular outcome trials (CVOTs) with SGLT-2 inhibitors to assess their cardiorenal efficacy in patients with and without T2D
Summary
Inhibitors of the sodium–glucose co-transporter 2 (SGLT-2) were initially developed for the treatment of type 2 diabetes (T2D) for their effect of lowering blood glucose levels through increased excretion of glucose in the urine [1]. Giugliano et al Cardiovascular Diabetology (2021) 20:236 trials [2], patients with T2D were typically divided by the presence or absence of established cardiovascular disease Once their efficacy in reducing the risk of heart failure or progression of chronic kidney disease was ascertained [3,4,5,6] and thought to be largely independent of baseline and time-dependent changes in glycated hemoglobin [7], the hypothesis emerged that their cardiorenal benefits might not necessarily be due to glucose lowering and might be found in individuals without diabetes. One key question is how the effects of SGLT-2 inhibitors compared in patients with and without T2D, and whether the findings of the completed trials support the hypothesis that SGLT-2 inhibition might be an effective treatment for patients with heart failure, including those without diabetes The aim of this meta-analysis was to provide an update of all large CVOTs with SGLT-2 inhibitors to assess their cardiorenal efficacy in patients with and without T2D. The purpose of this study is to provide an update of all large cardiovascular outcome trials (CVOTs) with SGLT-2 inhibitors to assess their cardiorenal efficacy in patients with and without T2D
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