Exploring the comparative cardiovascular death benefits of sodium–glucose cotransporter 2 inhibitors in type 2 diabetes: a frequentist and Bayesian network meta-analysis-based scoring

BACKGROUND AND AIMS: Cardiovascular death (CV death) is the most objective component of the primary or secondary endpoint in cardiovascular outcome trials (CVOTs) conducted with sodium–glucose cotransporter 2 inhibitors (SGLT-2is). CV death is often incorporated into primary composite outcomes. It is combined with major adverse cardiovascular events (MACEs) in trials with atherosclerotic cardiovascular disease (ASCVD) at baseline and with hospitalization due to heart failure (hHF) in trials with heart failure at baseline. Unlike the primary composites, CV death reduction by itself demonstrated significant variations among the CVOTs with SGLT-2is. Moreover, the impact of the individual agents within the SGLT-2i group on the reduction in CV death has not been explored objectively. This network meta-analysis was undertaken to construct a hierarchy based on indirect pairwise comparisons and rankings among the individual agents within SGLT-2is. METHODS: A Cochrane library-based web search yielded 13 randomized controlled trials for analysis. Stata/BE 17.0 and RStudio 2022.07.1 Build 554 software were used to conduct a frequentist and Bayesian network meta-analysis. The effect size was assessed based on the risk ratio (RR). Ranking of the individual agents was performed with a frequentist approach (P-score and a multidimensional scaling [MDS] rank system) and a Bayesian ranking (surface under the cumulative ranking [SUCRA]). RESULTS: Regarding the overall data, SGLT-2is reduced the CV death risk by 12% (RR: 0.88, 95% CI 0.80–0.96). All three scoring methods resulted in empagliflozin scoring the highest. There was a 15% RR reduction in CV death (95% CI 0.71–1.02) in the ASCVD and multiple cardiovascular risk factor (MRF) groups and an 11% RR reduction in the HF group, with empagliflozin ranking the highest in the former group and dapagliflozin in the latter. CONCLUSIONS: Empagliflozin ranked the highest compared to the other SGLT-2is in the overall population and the trials including type 2 diabetes (T2D) patients with ASCVD or MRF at baseline, while dapagliflozin ranked the highest in the trials of patients with HF at baseline. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022381556, identifier CRD42022381556.