Sodium-glucose co-transporter 2 ( SGLT2 ) receptors are primarily located in the proximal convoluted tubule of the nephron. These receptors are responsible for almost 90% to 95% of tubular reabsorption of the glucose in the nephron.
In patients with diabetes mellitus, due to upregulation of SGLT2 receptors, glucose reabsorption is further increased.
The FDA ( Food and Drug Administration ) has approved SGLT2 inhibitors, such as Canagliflozin ( Invokana ), Empagliflozin ( Jardiance ), Dapagliflozin ( Forxiga ), and Ertugliflozin ( Steglatro ), for the treatment of type 2 diabetes.
In addition to their positive effect on blood glucose, additional cardioprotective and renoprotective functions have been demonstrated in major trials such as EMPA-REG OUTCOME, CANVAS, DECLARE-TIMI-58, and CREDENCE.
Unlike other antihyperglycemic drugs, reduction in hospitalization for heart failure was also seen as a class effect with this group, mechanisms of which are probably multifactorial.
Subgroup analysis from these major trials indicated a reduction in progression of nephropathy and heart failure readmission with SGLT2 inhibitors.
Although this unique property of Canagliflozin was further analyzed in the CREDENCE trial, similar trials for Empagliflozin ( EMPERIAL-Reduced and EMPERIAL-Preserved ) and Dapagliflozin ( DAPA-HF ) are currently underway.
Recently released phase III results from DAPA-HF trial have indicated that Dapagliflozin shows significant reduction in death due to cardiovascular causes and hospitalization in heart failure compared with the placebo, in both diabetics and nondiabetics. ( Xagena )
Ghosh RK et al, Am J Cardiol 2019; 124:1790-1796