Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117–28. https://doi.org/10.1056/NEJMoa1504720.

Article  CAS  PubMed  Google Scholar 

Rosenstock J, Seman LJ, Jelaska A, et al. Efficacy and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, as add-on to metformin in type 2 diabetes with mild hyperglycaemia. Diabetes Obes Metab. 2013;15:1154–60. https://doi.org/10.1111/dom.12185.

Article  CAS  PubMed  Google Scholar 

Rosenstock J, Marquard J, Laffel LM, et al. Empagliflozin as adjunctive to insulin therapy in type1 diabetes: the EASE trials. Diabetes Care. 2018;41:2560–9. https://doi.org/10.2337/dc18-1749.

Article  CAS  PubMed  Google Scholar 

Laffel LM, Danne T, Klingensmith GJ, et al, on behalf of the DINAMO Study Group. Efficacy and safety of the SGLT2 inhibitor empagliflozin versus placebo and the DPP-4 inhibitor linagliptin versus placebo in young people with type 2 diabetes (DINAMO): a multicentre, randomised, double-blind, parallel group, phase 3 trial. Lancet Diabetes Endocrinol. 2023;11:169–181. https://doi.org/10.1016/S2213-8587(22)00387-4

Anker SD, Butler J, G. Filippatos G, et al. for the EMPEROR-Preserved Trial Investigators. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021;385:1451–1461. https://doi.org/10.1056/NEJMoa2107038

Packer M, Anker SD, J. Butler J, et al. for the EMPEROR-Reduced Trial Investigators. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020;383:1413–1424. https://doi.org/10.1056/NEJMoa2022190

Abraham WT, Lindenfeld J, Ponikowski P, et al. Effect of empagliflozin on exercise ability and symptoms in heart failure patients with reduced and preserved ejection fraction, with and without type 2 diabetes. Eur Heart J. 2021;42:700–10. https://doi.org/10.1093/eurheartj/ehaa943.

Article  CAS  PubMed  Google Scholar 

Voors AA, Angermann CE, Teerlink JR, et al. The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial. Nat Med. 2022;28:568–74. https://doi.org/10.1038/s41591-021-01659-1.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Butler J, Jones WS, Udell JA, et al. Empagliflozin after acute myocardial infarction. N Engl J Med. 2024;390:1455–66. https://doi.org/10.1056/NEJMoa2314051.

Article  CAS  PubMed  Google Scholar 

Meinert CL. Masked monitoring in clinical trials—blind stupidity? N Engl J Med. 1998;338:1381–2. https://doi.org/10.1056/NEJM199805073381911.

Article  CAS  PubMed  Google Scholar 

Fleming TR, DeMets DL, Roe MT, et al. Data monitoring committees: promoting best practices to address emerging challenges. Clin Trials. 2017;14:115–23. https://doi.org/10.1177/1740774516688915.

Article  PubMed  PubMed Central  Google Scholar 

Pocock S, Wang D, Wilhelmsen L, Hennekens CH. The data monitoring experience in the candesartan in heart failure assessment of reduction in mortality and morbidity (CHARM) program. Am Heart J. 2005;149:939–43. https://doi.org/10.1016/j.ahj.2004.10.038.

Article  CAS  PubMed  Google Scholar 

Kaul S. Is the mortality benefit with empagliflozin in type 2 diabetes mellitus too good to be true? Circulation. 2016. https://doi.org/10.1161/CIRCULATIONAHA.116.022537.

Article  PubMed  Google Scholar 

O’Neill RT. Secondary endpoints cannot be validly analyzed if the primary endpoint does not demonstrate clear statistical significance. Control Clin Trials. 1997;18:550–6. https://doi.org/10.1016/s0197-2456(97)00075-5.

Article  PubMed  Google Scholar 

Pocock SJ, Stone GW. The primary outcome fails—what next? N Engl J Med. 2016;275:861–70. https://doi.org/10.1056/NEJMra1510064.

Article  Google Scholar 

Anscombe FJ. On estimating binomial response relations. Biometrika. 1956;43:461–4. https://doi.org/10.1093/biomet/43.3-4.461.

Article  Google Scholar 

Buhr KA, Downs M, Rhorer J, Bechhofer R, Wittes J. Reports to independent data monitoring committees: an appeal for clarity, completeness, and comprehensibility. Ther Innov Regul Sci. 2018;52(4):459–68. https://doi.org/10.1177/2168479017739268.

Article  PubMed  Google Scholar 

Welty FK, Rajai N, Amangurbanova M. Comprehensive review of cardiovascular complications of coronavirus disease 2019 and beneficial treatments. Cardiol Rev. 2022;30(3):145–57. https://doi.org/10.1097/CRD.0000000000000422.

Article  PubMed  Google Scholar 

R Core Team. R: a language and environment for statistical computing. R Foundation for Statistical Computing. 2018. Vienna, Austria

Xie Y, Allaire J, Grolemund G. R markdown: the definitive guide. Boca Raton: Chapman and Hall/CRC; 2018.

Book  Google Scholar 

Pitt B, Pfeffer MA, Assmann SF, et al. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. 2014;370:1383–92. https://doi.org/10.1056/NEJMoa13137.

Article  CAS  PubMed  Google Scholar