SGLT Inhibitors

A promising new class of oral hypoglycemic agents for type 2 diabetes, the SGLT inhibitors, are on the horizon. As they work on the kidney, and potentially have renal side effects, it may be helpful to review them.

These agents work by inhibiting the SGLT2 glucose transporter found in the S1 segment of the proximal tubule, responsible for 90% of glucose reabsorption in the kidney. They work by causing dose-dependant renal glycosuria, lowering both plasma glucose levels and insulinemia in animal models. Agents have the suffix -gliflozin, and examples include dapagliflozin and sergliflozin. Here's a recent review.

Interestingly, humans with loss-of-function mutations in SGLT2 live into adulthood, but experience systemic hypotension with markedly elevated renin levels, hypernatremia and metabolic alkalosis. This seems to be driven by renal sodium wasting occurring in association with glycosuria. These phenomena could also possibly occur as side effects of these drugs. Whether this side effect is a blessing (through improved BP and volume control) or a curse (through an adverse interaction with ACE inhibitors) remains to be seen. But with over 20 prototypic agents in the drug development pipeline, we'll definitely be hearing more about them.