Current updates of sodium-glucose cotransporter-2 inhibitor effects on atherosclerosis: a systematic review and meta-analysis of randomized controlled trial

Introduction: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are an emerging therapy to prevent at-herosclerotic cardiovascular disease (ASCVD) progression in diabetic patients. This study aims to demonstrate current evidence of SGLT2i’s role in clinical and subclinical atherosclerosis. Material and methods: Systematic randomized controlled trials (RCTs) searching was conducted in Cochrane, PubMed, EMBASE, and MEDLINE. Outcomes extracted from clinical and subclinical atherosclerosis studies. Results: In total, 11 clinical effects and 12 subclinical atherosclerosis studies were included. Meta-analysis was performed on 4 clinical effect studies. Pooled analysis showed SGLT2i significantly decreased MACE (RR 0.92; 95% CI 0.87–0.98; p = 0.03; i2 = 18%), HHF (RR 0.71; 95% CI 0.63–0.80; p < 0.0001; i2 = 0%), and renal outcome (RR 0,73; 95% CI 0.67–0.79; p < 0.0001; i2 = 17%) with no effect on CV death (RR 0,72; 95% CI 0.67–0.78; p < 0.0001; i2 = 32%) and increased amputation rate (RR 1.35; 95% CI 1.05–1.73; p = 0.02; i2 = 43%) compared to placebo. Subgroup analysis from those 4 RCTs showed that SGLT2i benefits are unaffected by age, history of HF, and PAD status. Two RCTs specifically studied the SGLT2i effect on PAD patients with results showing the beneficial effect on MACE and HHF is not significant while showing significant benefit on CV death and renal outcome. The amputation rate was not significantly different in PAD patients. Most studies of subclinical atherosclerosis showed benefits on PWV improvement, conflicting results on FMD, and no benefit on IMT. Conclusions: SGLT2i showed benefits in reducing MACE, HHF, and renal outcome in diabetic patients with ASCVD with adverse events of increased amputation rate. Subclinical atherosclerosis studies showed varied conflicting results.