Cardiovascular outcomes trials: a paradigm shift in the current management of type 2 diabetes.

The beneficial effect of canagliflozin on 3P-MACE was confirmed in patients with T2D and CKD in a subsequent renal outcomes trial, CREDENCE (HR [95% CI] 0.80 [0.67–0.95], p = 0.01), which also showed a trend towards a reduction in CV deaths that neared significance (HR [95% CI] 0.78 [0.61–1.00], p = 0.05) [ 36 ].

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A reduced risk of all-cause death in patients with T2D was also noted in EXSCEL (exenatide) (HR [95% CI] 0.86 [0.77–0.97]) and PIONEER-6 (oral semaglutide) (0.51 [0.31–0.84]), although these results were only nominally significant, owing to the hierarchical testing plans used [ 15 , 33 ].

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