The SGLT2i-mediated regulation of cardiovascular and safety outcomes among patients with chronic kidney disease: A systematic review and meta-analysis of randomized controlled trials

Backgrounds: : To assess the impact of SGLT2i on the cardiovascular and safety outcomes of patients with chronic kidney disease (CKD). Methods: : Eligible articles were chosen via a systematic search of the PubMed, Embase, and Cochrane electronic databases. We screened for randomized placebo-controlled clinical trials (RCTs) investigating the outcome of SGLT2i on patients with CKD. The main cardiovascular outcomes were major adverse cardiovascular events (MACE), which involved non-fatal myocardial infarction, non-fatal stroke and cardiovascular death, cardiovascular death and hospitalization for heart failure. On the other hand, acute renal injury, hypoglycemia, diabetic ketoacidosis, and amputation were considered as safety indicators for this trial. Renal insufficiency was defined as eGFR<90 mL per minute per 1.73m 2 . In case the heterogeneity outcome index was ≥50%, we conducted sensitivity analysis on relevant data to ensure the reliability of our conclusions. Results: : Overall, 7 articles, involving 26739 total participants, conformed to our inclusion and exclusion criteria. Compared to placebo, SGLT2i significantly modulated cardiovascular outcomes MACE (OR: 0.76 95% CI: 0.68 to 0.86 I 2 40.7% P: 0.168), cardiovascular death (OR: 0.83 95% CI: 0.72 to 0.95 I 2 26.4% P: 0.236), and hospitalization for heart failure (OR: 0.67 95% CI: 0.60 to 0.76 I 2 0.0% P: 0.538), as well as safety outcomes, such as, acute renal injury (OR: 0.83 95% CI: 0.68 to 1.00 I 2 0.0% P: 0.576), hypoglycemia (OR: 0.88 95% CI: 0.73 to 1.07 I 2 18.4% P: 0.297), diabetes ketoacidosis (OR: 2.57 95% CI: 1.50 to 4.41 I 2 46.3% P: 0.133), and amputation (OR: 1.09 95% CI: 0.87 to 1.36 I 2 ; 0.0% P: 0.703). Conclusion: In patients with CKD, SGLT2i usage markedly diminished incidences of cardiovascular outcomes MACE, cardiovascular death and hospitalization for heart failure. In addition, it also reduced the related risks of safety outcomes, such as, acute renal injury, hypoglycemia, diabetic ketoacidosis, and amputation. However, since the safety outcome selection was not complete in this trial, further investigations are necessary to assess all safety outcomes among a larger patient population.