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Dr Mathew John, Trivandrum 20 November 2018

Sodium-glucose co-transporter 2 inhibitors (SGLT-2i) act by inhibiting SGLT-2 in the proximal tubule of the kidney, thereby increasing natriuresis and glucose excretion.
They have beneficial effects on weight, systolic BP and HbA1c.
Large cardiovascular outcomes trials (CVOTs) have found reductions in composite major adverse cardiac events (MACE), heart failure hospitalization, CV death and various composites of CV outcomes.
Most of the data regarding the long-term effects on the kidney are derived from the CVOTs: EMPA REG OUTCOME, CANVAS and DECLARE TIMI.
About 70-90% of subjects enrolled in CVOTs of SGLT-2i did not have diabetic kidney disease (DKD).
Mechanisms of renal protection with SGLT-2 blockers – Restoring tubuloglomerular feedback; reducing renal hypoxia; changes in renal substrate utilization; improvements in BP; improvements in glycemia; improvements in weight and reducing uric acid levels.
Key benefits of SGLT-2i in DKD – Retard the progression of eGFR in subjects with proteinuric DKD; retard the progression of microalbuminuria to macroalbuminuria; retard the progression of macroalbuminuria to ESRD; reduce the risk of new-onset albuminuria; reduce various CV outcomes in subjects with DKD.

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