SGLT2 inhibitors, originally developed for type 2 diabetes, have shown potential benefits beyond glycemic control, including cardiovascular, renal, and metabolic improvements in nondiabetic patients. A systematic review of 26 randomized controlled trials (RCTs) involving 35,317 participants found that SGLT2 inhibitors reduce cardiovascular mortality, hospitalization for heart failure, and improve renal outcomes such as slowing chronic kidney disease (CKD) progression and reducing albuminuria. These benefits were associated with an acceptable safety profile. The mechanisms include metabolic effects, reduction in cardiovascular and renal stress, and anti-inflammatory properties. SGLT2 inhibitors also showed significant improvements in metabolic parameters like body weight, BMI, and glucose tolerance in nondiabetic individuals. In CKD patients, SGLT2 inhibitors reduced the risk of CKD progression and improved renal function. However, the role of SGLT2 inhibitors in nondiabetic patients remains under investigation, with ongoing research needed to fully understand their long-term effects and mechanisms. The review highlights the potential of SGLT2 inhibitors as a first-line therapy for CKD and cardiovascular diseases, suggesting their inclusion in therapeutic guidelines for nondiabetic patients. Further studies are required to confirm their efficacy and safety in this population.SGLT2 inhibitors, originally developed for type 2 diabetes, have shown potential benefits beyond glycemic control, including cardiovascular, renal, and metabolic improvements in nondiabetic patients. A systematic review of 26 randomized controlled trials (RCTs) involving 35,317 participants found that SGLT2 inhibitors reduce cardiovascular mortality, hospitalization for heart failure, and improve renal outcomes such as slowing chronic kidney disease (CKD) progression and reducing albuminuria. These benefits were associated with an acceptable safety profile. The mechanisms include metabolic effects, reduction in cardiovascular and renal stress, and anti-inflammatory properties. SGLT2 inhibitors also showed significant improvements in metabolic parameters like body weight, BMI, and glucose tolerance in nondiabetic individuals. In CKD patients, SGLT2 inhibitors reduced the risk of CKD progression and improved renal function. However, the role of SGLT2 inhibitors in nondiabetic patients remains under investigation, with ongoing research needed to fully understand their long-term effects and mechanisms. The review highlights the potential of SGLT2 inhibitors as a first-line therapy for CKD and cardiovascular diseases, suggesting their inclusion in therapeutic guidelines for nondiabetic patients. Further studies are required to confirm their efficacy and safety in this population.