OBJECTIVES: Clinical trials conducted in type 2 diabetes (T2DM) treated with glucose-lowering drugs and examining cardiovascular-related outcomes have yielded mixed results. In this work we aimed to assess the relative treatment effect of empagliflozin versus sitagliptin and saxagliptin (dipeptidyl peptidase 4 (DPP-4) inhibitors) on cardiovascular-related outcomes in patients with T2DM.

METHODS: We conducted a systematic literature review to identify clinical trials assessing cardiovascular-related outcomes for sitagliptin, saxagliptin and empagliflozin treated patients with T2DM. A network meta-analysis for indirect treatment comparison was conducted in a Bayesian framework. Hazard ratios were computed for six cardiovascular-related outcomes to estimate relative efficacy of these agents.

RESULTS: Empagliflozin showed a statistically significant superiority over saxagliptin (HR: 0.60; 95% CrI 0.46-0.80), and sitagliptin (HR: 0.60; 95% CrI 0.46-0.79) to reduce the risk for cardiovascular-related mortality. Also for all-cause mortality, empagliflozin showed a statistically significant risk reduction compared to saxagliptin (HR: 0.61; 95% CrI 0.49-0.76), and sitagliptin (HR: 0.67; 95% CrI 0.54-0.83). A similar pattern was observed in the risk reduction for hospitalization due to hear failure, where empagliflozin was statistically significantly superior to saxagliptin (HR: 0.51; 95% CrI 0.37-0.70) and sitagliptin (HR: 0.65; 95% CrI 0.47-0.90). Empagliflozin was not statistically different to sitagliptin and saxagliptin with regard to the risk of a composite endpoint composed of death, stroke, or myocardial infarction.

CONCLUSIONS: In this indirect comparison to the DPP-4 inhibitors saxagliptin and sitagliptin, empagliflozin significantly lowered the risk of cardiovascular-related mortality, all-cause mortality, and hospitalizations due to heart failure.