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


  • Thomas Simon James Crabtree University Hospitals of Derby and Burton NHS Trust; University of Nottingham
  • Robert EJ Ryder Sandwell and West Birmingham Hospitals NHS Trust



Diabetes, Type 2, Heart Failure, SGLT-2, CVOT


Introduction: Type 2 diabetes is a condition which is frequently associated with macrovascular complications. Sodium-glucose linked transporter-2 inhibitors (SGLT2i) have been demonstrated to improve composite cardiovascular outcomes assessed via a 3-point Major Adverse Cardiovascular Events (MACE). Although they yield some benefit in reducing overall rates of cardiovascular death, stroke and myocardial infarction, it appears that the majority of the beneficial effects of SGLT2i drugs on composite outcomes are mediated by improvements in heart failure outcomes reducing cardiovas cular death. This effect has been noted across multiple different drugs in the SGLT2i class. The aim of this review was to synthesise current evidence from randomised controlled trials (RCTs) comparing SGLT2i with placebo in adults with type 2 diabetes mellitus. The outcomes of interest were hazard ratios compared with placebo for 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, Cohrane CENTRAL and CINAHL. RCTs comparing SGLT2i with placebo were eligible for inclu- sion, providing they contained results for at least the out- come of interest. Studies were reviewed for inclusion by the two authors and data extraction and bias assessments were performed using a modified Cochrane’s data extraction tool and bias assessment tool. Meta-analysis of hazard ratios (HRs) was performed in RevMan 5.4 using generic inverse variance and a fixed effects model.

Results: 3,212 records were identified of which 13 were even tually included, covering 11 clinical studies. The risk of hospitalisation for heart failure was significantly lower with SGLT2i compared to placebo (HR 0.69; 95% CI 0.64, 0.74). Inter-study heterogeneity was minimal (I2=0%) Only one study contained outcomes for death due to heart failure, but its results were not significant. No current studies report hazard ratios for heart failure diagnoses with SGLT2i use compared with placebo.

Conclusion: SGLT2i drugs reduce the rates of hospitalization  due to heart failure in people with type 2 diabetes. This may help mediate the improvements seen in composite cardiovas cular outcomes. More evidence is needed to support their use in reducing mortality due to heart failure and incidence rates of new heart failure in this high-risk cohort.



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