<h4>Objective</h4>To investigate the effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with diabetes with cardiovascular disease (CVD) or at high cardiovascular risk.<h4>Design</h4>Systematic review and meta-analysis of randomized controlled trials (RCTs).<h4>Data sources</h4>Pubmed, Embase, the Cochrane Library, and ClinicalTrial.gov from their inception to August 28, 2021.<h4>Review methods</h4>Randomized control trials (RCTs) assess the effects of SGLT2i in patients with diabetes with cardiovascular disease or at high cardiovascular risk. The gene discussed is SLC5A2; the disease is diabetes mellitus.