Are SGLT2 Inhibitors Linked to Amputation, Ketoacidosis Risk?

Use of sodium-glucose cotransporter 2 (SGLT2) inhibitors is associated with an increased risk of lower limb amputation and diabetic ketoacidosis, according to the results of a recent study.

Previous research has questioned the safety of SGLT2 inhibitors. In order to assess the association between these drugs and the risk of 7 serious adverse events, researchers conducted a propensity score matched cohort study involving 17,213 new users of SGLT2 inhibitors (dapagliflozin, 61%; empagliflozin, 38%; canagliflozin, 1%) and 17,213 new users of glucagon-like peptide 1 (GLP1) receptor agonists.

The primary outcome of the study was lower limb amputation, bone fracture, diabetic ketoacidosis, acute kidney injury, serious urinary tract infection, venous thromboembolism, and acute pancreatitis.

Overall, use of SGLT2 inhibitors was associated with a greater risk of lower limb amputation (incidence rate 2.7 v 1.1 events per 1000 person-years, hazard ratio 2.32) and diabetic ketoacidosis (incidence rate 1.3 v 0.6 events per 1000 person-years, hazard ratio 2.14,) compared with use of GLP1 receptor agonists. SGLT2 inhibitor use was not associated with increased risk of bone fracture, acute kidney injury, serious urinary tract infection, venous thromboembolism, and acute pancreatitis.

“In this analysis of nationwide registers from two countries, SGLT2 inhibitors, as compared with GLP1 receptor agonists, were associated with an increased risk of lower limb amputations and diabetic ketoacidosis, but not with other serious adverse events of current concern.”

—Michael Potts

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