What are SGLT2 inhibitors, and how do they work?
Sodium-GLucose co-Transporter 2 (SGLT2) inhibitors are a new class of antihyperglycemic agent. The first, canagliflozin, was approved by the FDA in March 2013, followed by dapagliflozin (January 2014) and empagliflozin (August 2014).
As glucose is filtered through the nephrons of the kidney, about 90% is reabsorbed via SGLT2 in the proximal tubule (SGLT1 is responsible for the remaining 10%) so that glucose calories are not eliminated through urine.1 In a healthy person, the renal glucose threshold is about 180 mg/dL.1 When blood glucose exceeds this level, glucose is excreted into the urine. However, in diabetic patients, this threshold is higher due to the up-regulation of SGLT2s (and other glucose transporters), which worsens hyperglycemia.1 SGLT2 inhibitors will reset the threshold, which in turn will increase glucosuria and thereby lower serum glucose.1
SGLT2 inhibitors lower A1C by about 0.7% to 0.8%.2 Independent of other mechanisms such as the degree of b-cell function or insulin resistance, these agents can be used regardless of the duration of diabetes3 if the GFR is intact (≥ 45 mL/min/1.73 m2 for canagliflozin and empagliflozin, ≥ 60 mL/min/ 1.73 m2 for dapagliflozin).4,5
What are the risks and benefits associated with these agents?