Cardiorenal Effects of SGLT2 Inhibitors: A Meta-Analysis of Randomized Controlled Trials

Type 2 diabetes (T2D) and hypertension are major causes of end-stage renal disease (ESRD) and cardiovascular complications. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, also known as gliflozins, initially developed as antidiabetic agents, have demonstrated significant cardiorenal protective effects independent of glycemic control. This meta-analysis aimed to evaluate their impact on the prevention of ESRD and major adverse cardiovascular events (MACE). A systematic review and meta-analysis were conducted in accordance with PRISMA 2020 guidelines. PubMed/MEDLINE, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched from 2008 to 2025. Randomized controlled trials comparing SGLT2 inhibitors with placebo were included. The primary outcomes were a composite renal endpoint (progression to ESRD, ≥50% decline in glomerular filtration rate, initiation of renal replacement therapy, or renal death) and MACE (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke). Statistical analyses were performed using RevMan 5.4, applying fixed- or random-effects models depending on heterogeneity (I²). Results were expressed as odds ratios (OR) with 95% confidence intervals (95% CI). A total of 13 randomized controlled trials including 90,413 participants were analyzed. SGLT2 inhibitors significantly reduced the risk of major renal events (OR = 0.68; 95% CI: 0.59–0.77; I² = 61%), major cardiovascular events (OR = 0.88; 95% CI: 0.83–0.93; I² = 44%), and all-cause mortality (OR = 0.89; 95% CI: 0.85–0.93). In conclusion, SGLT2 inhibitors confirm their major cardiorenal benefits, independent of glycemic control, significantly reducing progression to ESRD, major cardiovascular events, and overall mortality. These findings support their early use in patients at high cardiorenal risk, in line with recent international recommendations. Keywords : SGLT2 inhibitors; Gliflozins; End-stage renal disease; Type 2 diabetes; Hypertension; Cardiovascular outcomes; Meta-analysis; PRISMA