Background: Previous studies compared the cardiorenal efficacy of these two types of SGLT2 inhibitors; however, the findings are inconsistent and do not reflect the population of Type 2 diabetic Mellitus (T2DM) patients in Indonesia, which ranks fifth globally in diabetes prevalence. This study aims to evaluate the effects and safety of dapagliflozin and empagliflozin on cardiorenal risk factors in T2DM Indonesian patients over a 12-month. Methods: This study utilized a multicenter retrospective cohort to evaluate diverse cardiorenal risk factors, encompassing glycemic control, blood pressure, lipid profile, body weight, Body Mass Index (BMI), calculated 10-year Atherosclerotic Cardiovascular Disease (ASCVD) risk, and estimated Glomerular Filtration Rate (eGFR), alongside the safety profile of SGLT2is. Paired data analysis, comparative analysis between groups, and linear regression were conducted to adjust the confounding. Results: Both groups exhibited enhancements in HbA1c, Fasting Plasma Glucose (FPG), Systolic Blood Pressure (SBP), and Low-Density Lipoprotein Cholesterol (LDL-C). Improvements in BMI, Diastolic Blood Pressure (DBP), triglycerides, ASCVD risk, and High-Density Lipoprotein Cholesterol (HDL-C) were only seen in the dapagliflozin group. Although dapagliflozin was associated with greater reductions in body weight and BMI, these differences were not statistically significant after adjustment for confounding factors. No significant differences were observed in the average alteration of HbA1c, FPG, SBP, DBP, LDL-C, HDL-C, triglycerides, total cholesterol, eGFR, and ASCVD risk values. A comparable safety profile was found between groups. Conclusion: Dapagliflozin and Empagliflozin provide similar advantages in reducing cardiorenal risk and safety after 12 months of treatment in Indonesian patients with T2DM. Copyright: © 2025 Cokro F et al.