Sodium-glucose cotransporter-2 inhibitors (SGLT2i)

Sodium-glucose cotransporter -2 Inhibitors (SGLT-2 i) are newer drugs in the category of glucose-lowering drugs (antihyperglycemics). The SGLT-2 inhibitors block the SGLT-2 protein in proximal convoluted tubular cells (PCT cells) and inhibit the reabsorption of glucose and sodium, consequently reducing blood glucose and sodium levels.

The sodium glucose cotransporter-2 inhibitors work without affecting insulin secretion and action. These agents block glucose reabsorption in PCT and increase glucose excretion.

The SGLT-2 protein in PCT cells reabsorbs 90 % of filtered glucose.

SGLT-2 i examples -

-          Canagliflozin

-          Dapagliflozin

-          Empagliflozin

-          Ertugliflozin

The unabsorbed glucose and sodium are excreted in the urine, causing glucosuria and natriuresis, respectively. The glucose and sodium in urine pull more water along, causing osmotic diuresis. (water follows sodium and high solute areas)

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Indications of SGLT-2 inhibitors

SGLT2i is recommended for cardiovascular protection and delaying the progression of CKD in

-          Type 2 diabetes patients- it causes improvement in glucose control, reduced cardiovascular events, and slower CKD progression

-          Chronic kidney disease patients with eGFR > 20 ml/min per 1.73 m2

Important points to consider 

-          SGLT2i should be discontinued after initiation of replacement therapy.

-          SGLT-2 inhibitors should be discontinued before surgery, in prolonged fasting, and in critical medical illness with a higher risk of diabetic ketoacidosis.

SGLT-2 inhibitors benefit-

-          Reduced cardiovascular morbidity and mortality

-          Delayed CKD progression

-          Reduced blood pressure

-          Improved blood glucose control

-          Reduced fluid overload

-          Reduced risk of severe hyperkalemia

Side effects SGLT2i -

-          Ketoacidosis in type 2 diabetes

-          Lower limb amputation in type 2 diabetes

-          Increased risk of mycotic genital infections and urinary tract infection(UTI)

due to increased glucose in the urine

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