Commentary: Sodium Glucose Cotransporter 2 Inhibitors Reduce the Risk of Heart Failure Hospitalization in Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Abstract

We read with interest a meta-analysis (1) recently published in “Frontiers in Endocrinology” conducted by Zhang et al. In this study (1), Zhang and colleagues included eight randomized controlled trials (RCTs) comparing sodium-glucose cotransporter 2 inhibitors (SGLT2is) with placebo in patients with type 2 diabetes (T2D), and performed a meta-analysis to produce a pooled risk ratio (RR) and 95% confidence interval (CI) of SGLT2is versus placebo in reducing four cardiovascular endpoints. The authors in this study (1) concluded that SGLT2is would be an ideal choice for T2D patients with heart failure (HF) because they found that SGLT2is significantly reduced hospitalization for heart failure (HHF), major adverse cardiovascular events (MACE, a composite of cardiovascular death, myocardial infarction, or stroke), and cardiovascular death (CVD) versus placebo in T2D patients. On the other hand, they concluded that SGLT2is did not significantly affect all-cause death (ACD) because they produced the nonsignificant 95% CI of RR (SGLT2is versus placebo: RR 0.77, 95% CI 0.59-1.01) for ACD. In my opinion, these two conclusions are not rigorous. First, they cannot conclude that SGLT2is are an ideal choice for T2D patients with HF until they assess the efficacy of SGLT2is in this T2D subgroup of concomitant HF and identify the obvious effectiveness. Second, using RR as drug effect is not accurate enough; all the original studies included in the meta-analysis (1) used hazard ratio (HR) as drug effect and RR only contains the status of the occurrence of events, but fails to contain the time when events happen. HR, on the other hand, contains both. Thus, to validate and further extend the findings in the meta-analysis by Zhang et al. (1), we implemented this further quantitative synthesis study by carrying out a meta-analysis stratified by the status of HF based on the data of HRs and 95% CIs as reported in the original studies. Moreover, we additionally incorporated the recently published SOLOIST-WHF trial (2), in addition to the eight RCTs included in the study by Zhang et al. (1), because this trial (2) contributed to the relevant data of the T2D subgroup of concomitant HF.