Treatment of patients with type 2 diabetes (T2D) with the drug metformin greatly reduces diabetic complications and mortality.
Unfortunately, many patients on metformin therapy become hyperglycemic, which exacerbates insulin resistance and reduces ? cell function.
Dugs that target the sodium-glucose cotransporter-2 (SGLT2), which promotes glucose absorption in the kidney have been attractive for use a add-ons to metformin treatment.
In this issue of theJournal of Clinical Investigation, two research groups led by Ralph DeFronzo of the University of Texas and Ele Ferrannini of the University of Pisa independently report on clinical studies testing the ability SGLT2 inhibitors to reduce plasma glucose levels in T2D patients. SGLT2 inhibition increased glucose excretion in the urine (glycosuria), lowered fasting plasma glucose, and improved tissue insulin sensitivity. Surprisingly, the use of SLGT2 inhibitors resulted in an increase in endogenous glucose production and decreased insulin secretion, though overall pancreatic ? cell function was improved.
In a companion Commentary, William Cefalu of the Pennington Biomedical Research Center discusses the implications of these clinical studies for the future of T2D treatment.