Contrast-induced acute kidney injury (CI-AKI) remains a frequent and morbid complication following complex percutaneous coronary intervention (PCI), particularly in patients with diabetes or baseline renal dysfunction. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) exert pleiotropic vascular and renal effects, including natriuresis, improved microvascular perfusion, and attenuation of oxidative stress. While their cardiovascular benefits are established, their role in procedural nephroprotection is not well defined. This study evaluated whether periprocedural GLP-1RA therapy was associated with reduced CI-AKI incidence in patients undergoing complex PCI at a tertiary cardiovascular center.

We retrospectively analyzed 386 consecutive patients who underwent complex PCI between July 2023 and June 2025. Complex PCI included left main, bifurcation, chronic total occlusion, or implantation of ≥ 2 stents. Patients who received chronic GLP-1RA therapy within 30 days before PCI (semaglutide, liraglutide, or dulaglutide) were compared with matched controls not on GLP-1RA. Propensity score matching (1:2) balanced baseline characteristics including diabetes status, renal function, and contrast load. The primary endpoint was CI-AKI, defined as a serum creatinine rise ≥ 0.3 mg/dL or ≥ 50 % within 48 hours post-procedure. Secondary endpoints included in-hospital major adverse cardiac events (MACE), contrast volume, and length of stay. Creatinine was measured at baseline (≤ 24 h pre-PCI) and at 24 ± 6 h and 48 ± 6 h post-PCI; all patients received standardized isotonic saline hydration (1 mL/kg/h, or 0.5 mL/kg/h for LVEF ≤ 35 % or eGFR < 45 mL/min/1.73 m²) and low- or iso-osmolar contrast per protocol. Covariates for matching/adjustment included age, sex, HbA1c, eGFR, anemia, heart failure/LVEF, peri-procedural hypotension, SGLT2 inhibitor and ACEi/ARB/MRA use, statin intensity, access site (radial/femoral), lesion complexity (CTO/left main/bifurcation), and contrast volume. Per institutional anesthesia policy, patients on GLP-1RAs underwent aspiration-risk screening with adherence to fasting standards. Post-match comparisons used Fisher’s exact test for categorical variables and Mann–Whitney U for non-normally distributed continuous variables; multivariable logistic regression was limited to prespecified covariates to maintain events-per-variable ≥ 10.

After matching, 88 patients receiving GLP-1RA were compared with 176 controls. CI-AKI occurred in 5.7 % vs 14.8 %, respectively (p = 0.03). Mean contrast volume was similar (176 ± 48 mL vs 180 ± 50 mL; p = 0.56), yet post-procedural creatinine rise was smaller in the GLP-1RA group (0.07 ± 0.14 mg/dL vs 0.19 ± 0.22 mg/dL; p < 0.01). Rates of MACE and in-hospital bleeding were comparable. Median hospital stay was shorter (2 days [IQR 1–3] vs 3 days [IQR 2–4]; p = 0.02). The absolute risk reduction for CI-AKI was 9.1 % (95 % CI −2.3 to 18.3), corresponding to an approximate number needed to treat of 11 (for association only). On multivariate logistic regression, GLP-1RA therapy remained independently associated with lower CI-AKI risk (adjusted OR 0.35; 95 % CI 0.13–0.94; p = 0.036).

Chronic periprocedural GLP-1RA therapy was independently associated with a lower risk of CI-AKI after complex PCI without increasing adverse events. These findings highlight a potential reno-protective effect of GLP-1RAs beyond glycemic control and suggest a potential therapeutic avenue for high-risk coronary interventions. Prospective studies are warranted to validate these observations and define optimal integration into contemporary PCI pharmacotherapy.