The effect of sodium-glucose link transporter 2 inhibitors on heart failure end points in people with type 2 diabetes mellitus: a systematic review and meta-analysis

Sodium-glucose linked transporter 2 inhibitors (SGLT2i) have been demonstrated to improve cardiovascular outcomes. In particular, SGLT2i appear to be beneficial in improving heart failure outcomes in people with and without diabetes. The aim of this review was to synthesis current evidence from randomised controlled trials (RCTs) comparing SGLT2i to placebo in adults with type 2 diabetes mellitus. The outcomes of interest were rate hospitalisation due to heart failure (primary), death due to heart failure (secondary) and incidence rates of heart failure (secondary).Methods: Searches were performed using recognised terms in MedLine, EMBASE, Pubmed and CINAHL. Studies were included if they compared an SGLT2i to inhibitor in an RCT and contained data for an outcome of interest. Studies were reviewed for inclusion by two people (TSJC and REJR) and data extraction and bias assessment were performed using a modified Cochrane’s data extraction tool and bias assessment tool. Meta-analysis of hazard ratios was performed in RevMan 5.4 using generic inverse variance and a fixed effects model where possible.Results: 2,850 records were identified of which 11 were eventually included, covering 9 clinical studies. Eight of these were suitable for meta-analysis for the outcome of hospitalisation due to heart failure – the pooled hazard ratio was found to be 0.69 (95% CI 0.63, 0.75). Interstudy heterogeneity was minimal (I2 0%) Only one study contained outcomes for death specifically due to heart failure, but its results were not significant. No current studies report incidence rates of new heart failure diagnosis.Conclusion: SGLT2is reduce the rates of hospitalisation due to heart failure in people with type 2 diabetes. This may help mediate the improvements seen in all cardiovascular outcomes, especially when assessed as a composite. More evidence is needed to support their use in reduce mortality due to heart failure and incidence rates of new heart failure in this high-risk cohort.