SGLT2 inhibitors and cardiovascular and renal outcomes: a meta-analysis and trial sequential analysis

Influence of endpoint definitions on the effect of empagliflozin on major renal outcomes in the EMPEROR‐Preserved trial

“…Our results indicate that the definition of a major renal outcome can influence conclusions concerning the effect of a treatment on the progression of kidney disease in patients with heart failure. In the EMPEROR‐Preserved trial, we found a discordance between the effects of empagliflozin on heart failure hospitalizations and renal outcomes using the EMPEROR definition of a kidney event, but we noted a concordance between the heart failure and renal effects of SGLT2 inhibition (overall and in prespecified subgroups) when we used a more conventional definition, a finding that is closely aligned with observations of the effects of these drugs in large‐scale trials in type 2 diabetes 6,7 . Further exploration of these findings is warranted.…”

“…These discordances were extraordinarily puzzling, since in prior large-scale clinical trials, the effect of SGLT2 inhibitors on heart failure and renal outcomes had consistently tracked together. 6,7 To determine if the observed discordances were related to the definition that we specified for the identification of a renal event, we asked if our results would differ if we had prespecified the more conventional meta-analysis criteria for a renal event. Accordingly, we reanalysed the data from EMPEROR-Preserved using the meta-analysis definition.…”

“…When considering all patients with an ejection fraction >40%, empagliflozin reduced heart failure hospitalizations with no effect on major renal outcomes; when considering prespecified subgroups, ejection fraction significantly influenced the effect of empagliflozin on heart failure admissions but not on renal events. These discordances were extraordinarily puzzling, since in prior large‐scale clinical trials, the effect of SGLT2 inhibitors on heart failure and renal outcomes had consistently tracked together 6,7 …”

Response to letter to the editor regarding the article “SGLT2 inhibitors and cardiovascular and renal outcomes: a meta-analysis and trial sequential analysis” Cardiac, renal protection with SGLT2 inhibitors is evident but not in every diabetic patient

“…Qiu et al conducted a meta-regression analysis on our newly published updated meta-analysis [1] to assess the benefit of the sodium-glucose cotransporter 2 (SGLT2) inhibitors in subgroups of diabetic patients with regard to comorbidities such as atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), or heart failure (HF). Their findings are in agreement with our conclusion that confirmed the efficacy of SGLT2 inhibitors in reducing the incidence of CKD progression and cardiovascular events including HF hospitalization, cardiovascular mortality, all-cause mortality, and major adverse cardiovascular events.…”

“…Qiu et al provided the results that the effect of the SGLT2 inhibitors was consistent in diabetic patients with or without ASCVD, with or without CKD, and with or without HF. However, it must be emphasized that patients with diabetes who have none of the variables (ASCVD, CKD, and HF) were not included in any of the published clinical trials [1] and may not have cardiovascular and renal benefit from SGLT2 inhibitors.…”