Cardiovascular efficacy and safety of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists: a systematic review and network meta-analysis

Aims To compare the cardiovascular efficacy and safety of sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in adults with Type 2 diabetes. Methods Electronic databases were searched from inception to 22 October 2018 for randomized controlled trials designed to assess the cardiovascular efficacy of SGLT2 inhibitors or GLP-1RAs with regard to a three-point composite measure of major adverse cardiovascular events (non-fatal stroke, non-fatal myocardial infarction and cardiovascular mortality). Cardiovascular and safety data were synthesized using Bayesian network meta-analyses. Results Eight trials, including 60 082 participants, were deemed eligible for the network meta-analysis. Both SGLT2 inhibitors [hazard ratio 0.86 (95% credible interval 0.74, 1.01]) and GLP-1RAs [hazard ratio 0.88 (95% credible interval 0.78, 0.98)] reduced the three-point composite measure compared to placebo, with no evidence of differences between them [GLP-1RAs vs SGLT2 inhibitors: hazard ratio 1.02 (95% credible interval 0.83, 1.23)]. SGLT2 inhibitors reduced risk of hospital admission for heart failure compared to placebo [hazard ratio 0.67 (95% credible interval 0.53, 0.85)] and GLP-1RAs [hazard ratio 0.71 (95% credible interval 0.53, 0.93)]. No differences were found between the two drug classes in non-fatal stroke, non-fatal myocardial infarction, cardiovascular mortality, all-cause mortality or safety outcomes. Conclusions SGLT2 inhibitors and GLP-1RAs reduced the three-point major adverse cardiovascular event risk compared to placebo, with no differences between them. Compared with GLP-1RAs and placebo, SGLT2 inhibitors led to a larger reduction in hospital admission for heart failure risk.