OBJECTIVES: Trials designed to assess cardiovascular-related outcomes for type 2 diabetes (T2DM) patients treated with glucose-lowering drugs have yielded mixed results. We estimated the relative treatment effect of empagliflozin versus other glucagon-like peptide-1(GLP-1) receptor agonists on cardiovascular-related outcomes in patients with T2DM.

METHODS: A systematic literature review was conducted on 30 November 2016 to identify clinical trials designed to assess cardiovascular-related outcomes for empagliflozin and GLP-1 receptor agonists (liraglutide, lixisenatide, semaglutide and exenatide) in patients with T2DM. Bayesian network meta-analyses (NMAs) of hazard ratios for six cardiovascular-related outcomes were performed to estimate relative efficacy of these agents.

RESULTS: For all-cause mortality, empagliflozin was statistically significantly superior to liraglutide (HR: 0.80; 95% CrI 0.64-1.00), lixisenatide (HR: 0.72; 95% CrI 0.56-0.93), and semaglutide (HR: 0.65; 95% CrI 0.44-0.97). Empagliflozin showed a statistically significant lower risk of cardiovascular death over lixisenatide (HR: 0.63; 95% CrI 0.46-0.86). Empagliflozin showed significantly lower risk for hospitalization due to heart failure when compared to lixisenatide (HR: 0.67; 95% CrI 0.47-0.98), and semaglutide (HR: 0.59; 95% CrI 0.37-0.92). Empagliflozin was not significantly different in risk of major cardiovascular events, including composite endpoint, comprising cardiovascular death, non-fatal stroke, or non-fatal myocardial infarction. At date of literature search, no completed trials were identified for dulaglutide, albiglutide or exenatide.

CONCLUSIONS: Empagliflozin significantly lowered the risk of all-cause mortality, cardiovascular-related mortality, and hospitalizations due to heart failure when compared to GLP-1 receptor agonists.