SGLT2 INHIBITORS: FROM GLYCEMIC CONTROL TO CARDIO-RENAL PROTECTION EVLOEV KHARON KH1*, SNITSA DANIIL V2, PANKOV DANIL S2, GASPARYAN MARIYA A1, ZAYCEV MATVEY V3, KOIFMAN NATALYA A1, BUGLO ELENA A4, ZEFIROVA MARGARITA S2, RACHKOVA TAMARA A2, GURTIEV DMITRII A1, ZASEEVA VICTORIA V1, TOLMASOV JALOLIDDIN M1. 1NORTH-WESTERN STATE MEDICAL UNIVERSITY NAMED AFTER I.I. MECHNIKOV, SAINT-PETERSBURG, RUSSIA. 2SAINT-PETERSBURG STATE PEDIATRIC MEDICAL UNIVERSITY, SAINT-PETERSBURG, RUSSIA. 3PAVLOV FIRST SAINT-PETERSBURG STATE MEDICAL UNIVERSITY, SAINT-PETERSBURG, RUSSIA. 4INSTITUTE OF MEDICAL EDUCATION, ALMAZOV NATIONAL RESEARCH CENTRE, SAINT-PETERSBURG, RUSSIA. ABSTRACT. SODIUM-GLUCOSE COTRANSPORTER 2 (SGLT2) INHIBITORS WERE ORIGINALLY DEVELOPED AS GLUCOSE-LOWERING AGENTS FOR PATIENTS WITH TYPE 2 DIABETES MELLITUS (T2DM). HOWEVER, A GROWING BODY OF ROBUST CLINICAL EVIDENCE HAS DEMONSTRATED THEIR PROFOUND CARDIOPROTECTIVE AND NEPHROPROTECTIVE EFFECTS THAT EXTEND BEYOND GLYCEMIC CONTROL. THIS REVIEW SUMMARIZES THE CURRENT UNDERSTANDING OF THE MECHANISMS UNDERLYING THESE BENEFITS AND THE CLINICAL IMPLICATIONS ACROSS A WIDE RANGE OF PATIENT POPULATIONS. WE DISCUSS LANDMARK CARDIOVASCULAR AND RENAL OUTCOME TRIALS, EVALUATE THE PHYSIOLOGICAL AND MOLECULAR MECHANISMS, INCLUDING HEMODYNAMIC MODULATION, ANTI-INFLAMMATORY AND ANTIFIBROTIC EFFECTS, AND IMPROVEMENTS IN MYOCARDIAL AND RENAL ENERGETICS, AND ASSESS THE ROLE OF SGLT2 INHIBITORS IN HEART FAILURE WITH REDUCED AND PRESERVED EJECTION FRACTION, AS WELL AS IN CHRONIC KIDNEY DISEASE WITH AND WITHOUT DIABETES. THE TRANSLATION OF THESE FINDINGS INTO CLINICAL GUIDELINES HAS RESHAPED THERAPEUTIC STRATEGIES IN BOTH ENDOCRINOLOGY AND CARDIOLOGY, UNDERSCORING THE IMPORTANCE OF SGLT2 INHIBITORS AS A CORNERSTONE IN CARDIORENAL PROTECTION.