Safety and efficacy of ertugliflozin on heart failure outcomes across cardiovascular diseases: a systematic review and meta-analysis

Abstract

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) improve cardiovascular outcomes in patients with heart failure (HF) and type 2 diabetes (T2D). However, the efficacy of individual SGLT2is, particularly ertugliflozin, remains less defined. This systematic review and meta-analysis aimed to synthesize evidence from randomized controlled trials (RCTs) evaluating the safety and cardiovascular efficacy of ertugliflozin in patients with HF or high cardiovascular risk. We searched PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials from inception to December 25, 2025, for RCTs comparing ertugliflozin to placebo in adults with cardiovascular disease or high cardiovascular risk. Primary outcomes were cardiovascular mortality, heart failure hospitalization (HFH), and left ventricular ejection fraction (LVEF). Secondary outcomes included left atrial volume index (LAVI), systolic and diastolic blood pressure (SBP, DBP), heart rate (HR), and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Data were analyzed using R version 4.5.2 with random- or fixed-effects models based on heterogeneity. Six RCTs comprising 8,752 participants met inclusion criteria. Risk of bias was low in three studies, raised some concerns in two, and was high in one. Compared with placebo, ertugliflozin was not associated with a significant reduction in cardiovascular mortality (RR 0.92, 95% CI [0.77, 1.10]; I 2 = 0%). No significant reductions were observed for heart failure hospitalization (RR 0.49, 95% CI [0.10, 2.33]; I 2 = 59.9%) or LVEF (MD 1.26%, 95% CI [− 0.27, 2.79]; I 2 = 0%). Certainty of evidence was very low for most of the outcomes. Ertugliflozin was not associated with a significant reduction in cardiovascular mortality and heart failure hospitalization. In addition, no significant improvement was observed in LVEF in this pooled analysis. Accordingly, given the very low certainty of evidence and variability in study quality, these findings should be interpreted cautiously. Larger, dedicated trials are needed to definitively establish the cardiovascular efficacy of ertugliflozin in heart failure populations. The protocol for this review was registered with PROSPERO (CRD420261303795).