Fig. 1

Cardiorenal and mortality benefits reported for SGLT2i and GLP-1 RA. a SGLT2i. CVOTs for empagliflozin, canagliflozin, dapagliflozin and ertugliflozin have all pointed to beneficial effects on HHF and renal function outcomes [2,3,4,5, 7, 11, 13], either in a population with T2D and established CVD, or in a broader population also including patients with T2D and high CV risk. Renal benefits included slower progression of renal function decline and, where reported, improved albuminuria outcomes. In addition, empagliflozin and canagliflozin CVOTs demonstrated a reduction in 3P-MACE, while empagliflozin alone showed reductions in CV death and death by any cause [1, 7]. Note that in some cases benefits were shown in exploratory analyses. Dedicated renal and heart HF studies are also shedding light on cardiorenal benefits with SGLT2i. In CREDENCE, canagliflozin reduced HHF and renal events in patients with T2D and CKD (and showed a trend towards reduced CV deaths that did reach significance) [6], while in DAPA-HF, CV death, HHF and death by any cause were all reduced with dapagliflozin in patients with HFrEF, with or without T2D [9]. While this manuscript was under review, new publications have also shown that dapagliflozin improved a composite of renal and CV outcomes in patients with CKD, with or without T2D, in DAPA-CKD [20], and that empagliflozin reduced the risk of a composite of CV death or HHF in patients with HFrEF, with or without T2D, in EMPEROR-Reduced [21] (not shown). b GLP-1 RA. Some, but not all, GLP-1 RA CVOTs have shown cardiorenal benefits in patients with T2D and established CVD or high CV risk. Among injectable GLP-1 RA, liraglutide, semaglutide and dulaglutide CVOTs have all shown benefits in 3P-MACE and albuminuria outcomes [14, 15, 17, 18, 122, 123]. In addition, liraglutide reduced the risks of CV death and death by any cause, while semaglutide and dulaglutide reduced the risk of stroke. Once-weekly exenatide showed a trend towards a 3P-MACE benefit that did not reach significance in its CVOT, and also suggested reduced risks of death by any cause and albuminuria [19, 124]. Finally, a CVOT on the oral formulation of semaglutide suggested reduced risks of CV death and death by any cause [16]. For all CVOTs, patients in both placebo and treatment arms also received standard of care. Outcome definitions and inclusion criteria varied between CVOTs. Not all outcomes were primary outcomes, and findings may in some cases be of nominal significance only due to multiple testing, e.g. position in a prespecified hierarchy of statistical tests. Only marketed medications are shown