SGLT2 Inhibitors Tied to Increased Risk for Amputation, Diabetic Ketoacidosis

By Amy Orciari Herman

Edited by Susan Sadoughi, MD, and Richard Saitz, MD, MPH, FACP, DFASAM

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are associated with twice the risk for lower limb amputation and diabetic ketoacidosis relative to comparator diabetes drugs, an observational study in The BMJ suggests.

Using 2013–2016 data from Swedish and Danish registries, researchers compared adverse event rates between 17,000 adults newly prescribed SGLT2 inhibitors and 17,000 matched patients who received glucagon-like peptide-1 (GLP-1)-receptor agonists. Overall, lower limb amputation occurred more often with SGLT2 inhibitors than GLP-1-receptor agonists (2.7 vs. 1.1 events per 1000 person-years), as did diabetic ketoacidosis (1.3 vs. 0.6).

In contrast, rates of bone fracture, acute kidney injury, serious urinary tract infection, venous thromboembolism, and acute pancreatitis did not differ between the groups.

Of note, dapagliflozin and empagliflozin accounted for 99% of SGLT2 inhibitor use in the study. A third SGLT2 inhibitor, canagliflozin, already has a boxed warning due to the amputation risk among patients with or at risk for cardiovascular disease.