Jia Liao, Yang Chen, Zhiyu Ling, Helmut Pürerfellner, Martin Martinek, Michael Derndorfer, Johannes Niel, Ramin Ebrahimi, Matthias Heukäufer, Sarah Janschel, Davide Di Vece, Klaus Empen, Astrid Hummel, Bishwas Chamling, Piotr Futyma, Fahim Ebrahimi, Márcio G. Kiuchi, Shaowen Liu, Yuehui Yin, Alexandra Schratter, Willem‐Jan Acou, Philipp Sommer, Boris Schmidt, Julian K. R. Chun, Christian Meyer, Marcus Dörr, Christian Templin, Shaojie Chen

• Aims Sodium–glucose co‐transporter inhibitors (SGLTis) have cardiovascular protective effects. We aimed to assess the effects of SGLTis on individual hard clinical endpoints and quality of life (QoL) in patients with cardiovascular risk factors. Methods and Results Data was searched in PubMed, Embase, Cochrane Library and clinicaltrials.gov databases up to February 2024. Randomized controlled trials (RCTs) comparing SGLTis with placebo were included. The primary outcomes were individual hard clinical endpoints (Subset A) and QoL (Subset B). For Subset A, 13 RCTs including 90 413 patients were enrolled (age 66 ± 10.1 years, 35.7% female, follow‐up 2.4 ± 0.3 years); as compared with placebo, SGLTis were associated with significantly lower risk of all‐cause mortality [risk ratio (RR): 0.90, 95% confidence interval (CI): 0.86–0.94, P < 0.01], cardiovascular mortality (RR: 0.87, 95% CI: 0.82–0.92, P < 0.01), hospitalization for heart failure (HF) (RR: 0.72, 95% CI: 0.68–0.76, P < 0.01), HF events (RR: 0.72, 95% CI: 0.68–0.75, P < 0.01), hospitalization for any cause (RR: 0.91, 95% CI: 0.88–0.93, P < 0.01) and myocardial infarction (MI) (RR: 0.92, 95% CI: 0.85–0.99, P = 0.03). Notably, the favourable effect of SGLTis on all‐cause mortality was more pronounced in younger (<65 years) patients (RR: 0.86, 95% CI: 0.81–0.92) and in studies with less female (RR: 0.84, 95% CI: 0.79–0.90). The favourable effect of SGLTis on MI was only observed in patients who received sotagliflozin (RR: 0.47, 95% CI: 0.31–0.73). For Subset B, nine RCTs including 2552 HF patients were enrolled (age 67.8 ± 12.4 years, 36.4% female, follow‐up 3.4 ± 1.9 months); SGLTis were associated with significant improvement in QoL as compared with placebo. Conclusions In patients with a broad spectrum of cardiovascular risk factors, SGLTis substantially improve individual hard clinical outcomes and QoL.