SGLT2 inhibitors and risk reduction for mortality in high-risk patients: a meta-analysis of randomized controlled trials

Background: The aim of this paper is to assess the impact of sodium-glucose cotransporters-2 (SGLT2) inhibitors on all-cause and cardiovascular (CV) death in high-risk patients and compare the efficacy of empagliflozin and dapagliflozin.
Methods: PubMed was queried from inception to the last week of September 2023 for randomized controlled trials that compared SGLT2 inhibitors’ empagliflozin or dapagliflozin with placebo and included patients with heart failure (HF), type 2 diabetes mellitus (T2DM), or chronic kidney disease (CKD). The outcome of interest was CV death or all-cause death. Hazard ratios (HR) with 95% confidence intervals (CI) were pooled using a random effect model, and forest plots were created to analyze the results visually. A chi-square test was performed to assess subgroup differences between empagliflozin and dapagliflozin.
Results: Eight trials (N=55,818) were included in our analysis, namely EMPA-REG, EMPEROR-Reduced, EMPEROR-Preserved, EMPA-KIDNEY, DECLARE-TIMI, DAPA-HF, DELIVER and DAPA-CKD. Pooled analysis demonstrated that compared to placebo, SGLT2 inhibition reduced the risk of CV death (SGLT2i arm = 1405 events, 29,089 total patients; placebo arm = 1515 events, 26,729 total patients; HR: 0.85; 95%CI: 0.79-0.93, p<0.001) and all-cause death (SGLT2i arm = 2,491 events, 29,062 total patients; placebo arm= 2,625 events, 26,729 total patients; HR: 0.86; 95% CI 0.79-0.95, p=0.002) in high-risk patients identified as having either T2DM, HF, or CKD. No differences were observed in the effect of empagliflozin and dapagliflozin on CV death (HRempagliflozin: 0.81; 95% CI 0.68-0.97, HRdapagliflozin: 0.88; 0.82-0.95, p=0.39) and all-cause death (HRempagliflozin: 0.86; 95% CI 0.73-1.02, HRdapagliflozin: 0.87; 0.78-0.97, p=0.94).
Conclusions: SGLT2 inhibitors reduce the risk of all-cause and CV death in high-risk patients. Notably, there were no discernible differences in the benefits of empagliflozin and dapagliflozin on these outcomes.