Acute vascular redox modulation by SGLT2 inhibition in non-diabetic patients

BACKGROUND: Coronary angiography induces oxidative stress through contrast media exposure and ionizing radiation, potentially contributing to vascular and renal injury. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) exert antioxidant and anti-inflammatory effects beyond glycemic control. We investigated whether a single pre-procedural dose of empagliflozin modulates oxidative stress and inflammatory glycosylation patterns in non-diabetic patients undergoing elective coronary angiography. METHODS: In this prospective, randomized, double-blind study, 60 patients undergoing elective coronary angiography were assigned to standard care or empagliflozin 10 mg administered 2 h before the procedure. Blood samples were collected at baseline, 4 h, and 24 h post-procedure. Total antioxidant capacity (TAC), oxidative DNA damage (alkaline comet assay), and N-glycosylation profiles of immunoglobulin G (IgG) and total plasma proteins were analyzed. Longitudinal changes were assessed using mixed-effects models with correction for multiple testing. RESULTS: Baseline characteristics and procedural variables were comparable between groups. Empagliflozin administration was associated with attenuation of oxidative DNA damage 24 h after angiography and stabilization of antioxidant capacity compared with standard care. Directional shifts in IgG N-glycosylation toward a less pro-inflammatory profile were observed in the intervention group, including reduced agalactosylated and core-fucosylated glycans and relative preservation of galactosylated structures. Similar modulatory trends were detected in total plasma protein glycosylation patterns. Although several glycomic changes did not reach statistical significance after correction for multiple testing, the overall biological signal consistently favored reduced oxidative and inflammatory activation in the empagliflozin group. CONCLUSIONS: A single pre-procedural dose of empagliflozin was associated with attenuation of oxidative stress-related DNA damage and modulation of inflammatory glycosylation patterns following coronary angiography. These findings suggest a potential peri-procedural cytoprotective role of SGLT2 inhibition that warrants confirmation in larger studies. TRIAL REGISTRATION: ISRCTN11022820. Registered 13 October 2025. Retrospectively registered.