SGLT2 inhibitor therapy in patients with type-2 diabetes mellitus: is acute kidney injury a concern?

Sodium-glucose co-transporter-2 (SGLT2) inhibitor drugs are effective for treatment of type-2 diabetes mellitus. These medications target the SGLT2 transporter in the proximal convoluted tubule to prevent reabsorption of filtered glucose, resulting in glucosuria. Other clinically meaningful benefits beyond glycemic control include reductions in blood pressure, weight, and albuminuria. Three large clinical trials and subsequent meta-analyses studying SGLT2 inhibitors demonstrated significant cardiovascular benefits including reductions in heart failure hospitalizations, as well as reduced risk of myocardial infarction, stroke, or cardiovascular death in patients with established atherosclerotic cardiovascular disease. In addition, these agents produced kidney benefits including significant reductions in worsening estimated glomerular filtration rate, progression to end-stage kidney disease, and progression of chronic kidney disease in patients with type-2 diabetes mellitus and albuminuric chronic kidney disease. However, despite these beneficial cardiovascular and kidney effects, numerous reports of acute kidney injury, including need for dialysis and death, have been reported to the FDA adverse events reporting system raising concern among providers and a warning announcement from the FDA. This review will examine the clinical effects of the SGLT2 inhibitor drugs, mechanisms behind both kidney protection and harm, and clinical recommendations for their use.