The Na⁺/glucose symporter 2 (SGLT2) belongs to a family of solute sodium symporters (SSS). SSS proteins cotransport Na⁺ with sugars, amino acids, inorganic ions and vitamins. Members of this family are important in human physiology and disease.

SGLT2 is composed of a central group of seven helices (TM2, TM3, TM4, TM7, TM8, TM9, and TM11) that contribute side-chain interactions for ligand selectivity, along with seven supporting helices that stabilize these central helices. A striking feature is two discontinuous TM helices, TM2 and the symmetrically related TM7, in the center of the protomer¹. The NH2 and COOH termini of the transporter are both extracellular.

Expression of SGLT2 mRNA occurs exclusively in the kidney and primarily in the first two segments of the proximal tubular system. SGLT2 is capable of reabsorbing about 90% of glucose from the primary urine produced in the kidneys.

SGLT2 symports a single Na⁺ molecule together with a glucose molecule. SGLT2 is selective for Na⁺ as the energizing cation. Apart from H⁺ and Li⁺, no other monovalent cation can replace Na⁺ to drive glucose transport².

Renal SGLT2 inhibitors are new antidiabetic drugs with an insulin-independent mechanism of action. They pose one remarkable advantage compared with already established antidiabetics by increasing urinary glucose excretion without inducing hypoglycemia and thereby promoting bodyweight reduction³.