Abstract Background and Aims GLP-1 receptor agonists are antihyperglycemic drugs that have shown an interesting cardio and nephroprotective effect beyond glycemic control and also induce weight loss, which is likely a facilitating element in the renal and cardioprotection of patients with elevated BMI. Patients with cardiorenal syndrome are often approached as particularly complex cases, which can lead to the underutilization of certain therapeutic groups. We have analyzed the use of semaglutide in patients followed in the CRU of Puerta de Hierro University Hospital to evaluate the drug's efficacy in glycemic and weight control and its safety profile. Method Retrospective real-life analysis performed in patients who received semaglutide while being under follow-up in the CRU, from January 21-December 22. Follow-up time was 6 months. Patients who had previously been on GLP1-AR treatment, on renal replacement therapy, or while waiting for any percutaneous or surgical cardiovascular procedure were excluded from the study. Results 41 patients, 14 on oral semaglutide and 24 on subcutaneous semaglutide were analyzed. Demographic data and main comorbidities are shown in the table and were similar in both formulations. 53% of the patients were on maximum semaglutide dose at the end of follow-up (59.3% sbc and 42.9% oral, p 0.3). Weight loss and decrease in HbA1C% were significant without differences between formulations. We observed a significant decrease in systolic blood pressure of 11.1 (18) p 0.007 also similar in both drug formulations. No significant modifications in renal parameters were observed during follow-up. Adverse events were observed in 9 patients (22%), mainly gastrointestinal intolerance, and were more frequent with oral formulation (50% vs. 7.4%, p 0.004). 6 patients (14%) stopped semaglutide treatment without differences between formulation groups. 3 patients experienced at least one episode of HF decompensation, but no other events, hospitalizations, or deaths were observed. 3 (7.9%) patients experienced an eGFR decrease of> 30% without differences among the formulation groups. Conclusion We conclude that semaglutide in both formulations is an excellent option for glycemic and weight control in CRS patients’ blood pressure, with an additional significant improvement in blood pressure control and a good safety profile in this special population.