Are SGLT2 Inhibitors Linked to Increased Risk of Diabetic Ketoacidosis?

Sodium–glucose cotransporter 2 (SGLT2) inhibitors were associated with an almost 2-times greater risk of diabetic ketoacidosis in patients with diabetes, according to a recent research letter.

The researchers identified 50,220 patients who had received a new prescription for an SGLT2 inhibitor and 90,132 patients who had received a new prescription for a dipeptidyl peptidase-4 (DPP4) inhibitor between April 1, 2013 and December 31, 2014 on the Truven MarketScan database. Hospitalization for diabetic ketoacidosis within 180 days after initiating treatment with an SGLT2 or DPP4 inhibitor was assessed as the primary outcome.
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Patients who were prescribed SGLT2 inhibitors were younger and had fewer comorbidities compared with patients who were prescribed DPP4 inhibitors, but were more likely to receive insulin.

Before propensity-score matching, the unadjusted rate of diabetic ketoacidosis within 180 days of initiation of an SGLT2 inhibitor was about twice the rate after initiation of a DPP4 inhibitor (4.9 events per 1000 person-years vs 2.3 events per 1000 person-years) (hazard ratio 2.1).

After propensity-score matching, the hazard ratio was 2.2 for patients taking SGLT2 inhibitors.

“Shortly after initiation, SGLT2 inhibitors were associated with approximately twice the risk of diabetic ketoacidosis as were DPP4 inhibitors, although cases of diabetic ketoacidosis leading to hospitalization were infrequent,” the researchers concluded. “The increased risk of diabetic ketoacidosis with SGLT2 inhibitors is among the factors to be considered at the time of prescribing and throughout therapy if patients present with symptoms suggestive of diabetic ketoacidosis.”

—Melissa Weiss

Reference:

Fralick M, Schneeweiss S, and Patorno E. Risk of diabetic ketoacidosis after initiation of an SGLT2 inhibitor [published online June 8, 2017]. N Engl J Med. doi:10.1056/NEJMc1701990.