Footnotes

^*In the EMPA-KIDNEY trial, a randomized, parallel-group, double-blind, placebo-controlled study of 6609 patients with CKD, the efficacy and safety of JARDIANCE^® 10 mg (n=3304) were evaluated vs placebo (n=3305). The primary endpoint was a composite of CV death or progression of kidney disease defined as end-stage kidney disease (the initiation of maintenance dialysis or receipt of a kidney transplant), a sustained decrease in the eGFR to <10 ml/min/1.73 m², a sustained decrease in eGFR of ≥40% from baseline, or death from renal causes. Patients treated with JARDIANCE^® experienced a 28% RRR in this endpoint (HR=0.72; 95% CI: 0.64, 0.82; p<0.001).<sup>2

†</sup>In the EMPEROR-Reduced trial, a randomized, double-blind, parallel-group, placebo-controlled study of 3730 patients with HFrEF, the efficacy and safety of JARDIANCE^® 10 mg (n=1863) were evaluated vs placebo (n=1867). Patients were adults with chronic heart failure (NYHA class II, III, or IV) and reduced ejection fraction (LVEF ≤ 40%). The primary endpoint in the EMPEROR-Reduced trial was a composite of CV death or HHF, analyzed as time to the first event. Patients treated with JARDIANCE^® experienced a 25% RRR in this endpoint (HR=0.75; 95% CI: 0.65, 0.86; p<0.001). In the EMPEROR-Preserved trial, a randomized, double-blind, parallel-group, placebo-controlled study of 5988 patients with HFpEF, the efficacy and safety of JARDIANCE^® 10 mg (n=2997) were evaluated vs placebo (n=2991). Patients were adults with chronic heart failure (NYHA class II, III, or IV) and preserved ejection fraction (LVEF> 40%). The primary endpoint in the EMPEROR-Preserved trial was a composite of CV death or HHF, analyzed as time to the first event. Patients treated with JARDIANCE^® experienced a 21% RRR in this endpoint (HR=0.79; 95% CI: 0.69, 0.90; p<0.001).<sup>3,4

‡</sup>The primary composite outcome in the EMPA-REG OUTCOME® trial was 3-point MACE, composed of death from CV causes, nonfatal MI, or nonfatal stroke, as analyzed in the pooled JARDIANCE^® group vs the placebo group. Patients were adults with insufficiently controlled T2D and CAD, PAD, or a history of MI or stroke. The 14% RRR in 3-point MACE (HR=0.86; 95% CI: 0.74, 0.99; p<0.001 for noninferiority; p=0.04 for superiority) was driven by a reduction in the risk of CV death (HR=0.62; 95% CI: 0.49, 0.77); there was no change in risk of nonfatal MI (HR=0.87; 95% CI: 0.70, 1.09) or nonfatal stroke (HR=1.24; 95% CI: 0.92, 1.67).5 § Adult patients with an eGFR ≥ 20, < 45 mL/min/1.73 m² ; or an eGFR ≥ 45, < 90 mL/min/1.73 m² with a uACR ≥ 200 mg/g.2 # Adult patients with insufficiently controlled T2D and CAD, PAD, or a history of MI or stroke.1,5 || In addition to reducing the risk of CV death when added to the standard of care, JARDIANCE^® also lowered HbA1c. In addition, JARDIANCE^® demonstrated reduction in weight and blood pressure. JARDIANCE^® is not indicated for weight loss or reduction of blood pressure.5 **CV death was part of the composite primary endpoint, 3-point MACE, in the EMPA-REG OUTCOME® trial (HR=0.86; 95% CI: 0.74, 0.99; p<0.001 for noninferiority; p=0.04 for superiority) and 38% RRR in CV death was achieved in the overall EMPA-REG OUTCOME® population for the duration of the trial (HR=0.62; 95% CI: 0.49, 0.77; p<0.001). There were no significant differences between the placebo and JARDIANCE ^® groups of nonfatal MI (HR=0.87; 95% CI: 0.70, 1.09; p=0.22) or nonfatal stroke (HR=1.24; 95% CI: 0.92, 1.67; p=0.16).^1,5

^††Pooled data from 10-mg and 25-mg doses of JARDIANCE^®; both doses showed a comparable reduction in the risk of CV death.<sup>1,2

‡‡</sup> Adult patients with chronic heart failure (NYHA class II, III, or IV) and reduced ejection fraction (LVEF ≤ 40%).<sup>3

§§</sup> Adult patients with chronic heart failure (NYHA class II, III, or IV) and preserved ejection fraction (LVEF > 40%).<sup>4

##</sup>JARDIANCE^® is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients of JARDIANCE^®. JARDIANCE^® should not be used in patients with type 1 diabetes or for the treatment of DKA. JARDIANCE^® should be used with caution in patients who may be a higher risk of ketoacidosis while taking JARDIANCE^®. In patients where DKA is suspected or diagnosed, treatment with JARDIANCE^® should be discontinued immediately. For use in renally impaired patients, please refer to the SmPC.<sup>1

||||</sup>Please see the Summary of Product Characteristics for dosing details.

References

1. JARDIANCE^® [summary of product characteristics]. Ingelheim am Rhein, Germany; Boehringer Ingelheim International GmbH.

2. Herrington WG, Staplin N, Wanner C, et al. EMPA-KIDNEY Collaborative Group. Empagliflozin in patients with chronic kidney disease. N Engl J Med. 2023;388(2):117-127. (EMPA-KIDNEY results and the publication’s Supplementary Appendix.)

3. Packer M, Anker SD, Butler J, et al; EMPEROR-Reduced Trial Investigators Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020;383(15):1413-1424. (EMPEROR-Reduced results and the publication’s Supplementary Appendix.)

4. Anker SD, Butler J, Filippatos G, et al; EMPEROR-Preserved Trial Investigators. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021;385(16):1451-1461. (EMPEROR-Preserved results and the publication’s Supplementary Appendix.)

5. Zinman B, Wanner C, Lachin JM, et al; EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117-2128. (EMPA-REG OUTCOME® results and the publication’s Supplementary Appendix.)

6. Kalra S, Aydin H, Sahay M, et al. Cardiorenal syndrome in type 2 diabetes mellitus—rational use of sodium-glucose cotransporter-2 inhibitors. Eur Endocrinol. 2020;16(2):113-121.

7. GBD Chronic Kidney Disease Collaboration. Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2020;395(10225):709-733.

8. McDonagh TA, Metra M, Adamo M, et al; ESC Scientific Document Group. 2023 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2023: 00, 1-13.

9. Davies MJ, Aroda VR, Collins BS, et al. Management of hyperglycemia in type 2 diabetes, 2022: a consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2022;45(11):2753-2786.

10. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Acad Cardiol. 2022;79(17):e263-e421.

11. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2013;3(1):1-150.

12. Inzucchi SE, Kosiborod M, Fitchett D, et al. Improvement in cardiovascular outcomes with empagliflozin is independent of glycemic control. Circulation. 2018;138(17):1904-1907.

CAD=coronary artery disease; CI=confidence interval; CKD=chronic kidney disease; CV=cardiovascular; CVD=cardiovascular disease; HF=heart failure; HFpEF=heart failure with preserved ejection fraction; HFrEF=heart failure with reduced ejection fraction; HHF= hospitalisation for heart failure; HR=hazard ratio; LVEF=left ventricular ejection fraction; MACE=major adverse cardiovascular events; MI=myocardial infarction; NYHA=New York Heart Association; PAD=peripheral artery disease; RRR=relative risk reduction; T2D=type 2 diabetes.