The cardioprotective effect of inhibitor sodium glucose transporter in patients undergoing chemotherapy: a systematic review and meta-analysis

Abstract Background Sodium-glucose co-transporter 2 (SGLT2) inhibitors are well known for the countless benefits in glycemic control and cardiovascular outcomes in patients with heart failure (HF), significantly reducing the risk of hospitalizations for HF and cardiovascular death, in addition to kidney protection. However the benefit of SGLT2 inhibitors in HF due cancer therapy-related cardiac dysfunction (CTRCD) is yet to be established. Purpose This systematic review and meta-analysis aimed to evaluate the cardioprotective effects of SGLT2 inhibitors in patients undergoing chemotherapy who are at risk of developing CTRCD. Methods We conduct a comprehensive search of PubMed, Embase and the Cochrane Central Register of controlled trials to identify randomized controlled trials (RCTs) and observational cohorts comparing the use of SGLT2 inhibitors versus control, in patients undergoing chemotherapy and reporting the following outcomes (1) Heart failure; (2) Heart failure hospitalizations; (3) All-cause mortality and as a safety outcome (4) acute kidney injury and (5) urinary tract infection. The statistical analysis was performed using RStudio (Version 4.2.2). Data were pooled and analyzed as risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was assessed using the I² statistic. Heterogeneity was assessed using the I² statistical. Results We included 27,165 patients from 1 RCTs and 11 observational cohorts, of whom 44.31% were in the SGLT2 inhibitor group. The patients mean age was 64.7 ± 10.9 years and 49.43% were male. The new HF events were significantly lower in patients using SGLT2 inhibitors compared to control group (RR: 0.26; 95% CI 0.13 to 0.53; p0.001; Fig 1a). Therefore, SGLT2 inhibitors statistically decreased the number of HF hospitalizations (RR: 0.46 ; 95% CI 0.30 to 0.72; p0.001; Fig 1b). Consequently, there was also a reduction in all-cause mortality events (RR: 0.47; 95% CI 0.34 to 0.63; p0.001; Fig 1c). In terms of safety outcomes, there was a renal protection with SGLT2 inhibitor, showed by a reduction in acute kidney injury (RR: 0.71; 95% CI 0.56 to 0.91; p0.007; Fig 2a) and a reduction in urinary tract infection (RR:0.54; 95% CI 0.40 to 0.71; p001; Fig 2b). Conclusion SGLT2 inhibitors reduced the risks of new-onset HF, HF hospitalizations, and all-cause mortality in CTRCD-risk patients, without worsening renal function or increasing urinary tract infections, suggesting a potential management strategy during chemotherapy.Main Outcomes Safety Outcomes