SGLT2 inhibitors and lower limb amputations – new data increases cause for concern

Sodium glucose cotransporter 2 (SGLT2) inhibitors are now an established option for treatment of type 2 diabetes, but there has been concern the possibility that these agents are associated with higher rates of lower limb amputation, as well as various other uncommon adverse effects. In a large study from Scandinavia that was recently published in the British Medical Journal, researchers examined specific outcomes associated with treament with dapagliflozin (61% of the cohort), empagliflozin (38%), canagliflozin (1%) and compared these to those treated with an active comparator (glucagon-like peptide 1 (GLP1) receptor agonists). Primary outcome measures were the rates for lower limb amputation, bone fracture, diabetic ketoacidosis, acute kidney injury, serious urinary tract infection, venous thromboembolism, and acute pancreatitis. The SGLT2 inhibitors were associated with an increased risk of lower limb amputation (incidence rate 2.7 v 1.1 events per 1000 person years, hazard ratio 2.32, 95% confidence interval 1.37 to 3.91 ) and diabetic ketoacidosis (1.3 v 0.6, 2.14, 1.01 to 4.52) but the rates of bone fracture, acute kidney injury, serious urinary tract infection, venous thromboembolism and acute pancreatitis were not found to be increased. Given the propensity for type II diabetes to be associated with increased risk of vascular complications, the former finding is of particular concern.