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. 2018 Aug;9(4):1491-1500.
doi: 10.1007/s13300-018-0456-7. Epub 2018 Jun 12.

Cardiovascular Safety of Empagliflozin Versus Dipeptidyl Peptidase-4 (DPP-4) Inhibitors in Type 2 Diabetes: Systematic Literature Review and Indirect Comparisons

Chakrapani Balijepalli  1 , Rohan Shirali  2 , Prashanth Kandaswamy  3 , Anastasia Ustyugova  3 , Egon Pfarr  3 , Søren S Lund  3 , Eric Druyts  2
Affiliations

Cardiovascular Safety of Empagliflozin Versus Dipeptidyl Peptidase-4 (DPP-4) Inhibitors in Type 2 Diabetes: Systematic Literature Review and Indirect Comparisons

Chakrapani Balijepalli et al. Diabetes Ther. 2018 Aug.

Erratum in

Abstract

Introduction: Clinical trials conducted in patients with 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 effects 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 of indirect treatment comparisons was conducted in a Bayesian framework. Hazard ratios (HR) and 95% credible intervals (CrI) were computed for six cardiovascular-related outcomes to estimate the relative efficacies 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. 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 heart failure, where empagliflozin was found to be 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 significantly different to sitagliptin and saxagliptin with regard to the risk of a composite endpoint composed of death, stroke or myocardial infarction.

Conclusion: 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.

Funding: Boehringer Ingelheim GmbH.

Keywords: Cardiovascular outcomes; DPP-4 inhibitors; Empagliflozin; Network meta-analysis; Saxagliptin; Sitagliptin.

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Figures

Fig. 1
Fig. 1
PRISMA flow diagram
Fig. 2
Fig. 2
Overall evidence network
Fig. 3
Fig. 3
Plots presenting indirect comparisons of empagliflozin versus other glucose-lowering drugs
See this image and copyright information in PMC

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