Doubled risk of diabetic ketoacidosis with SGLT2 inhibitors
Sodium-glucose cotransporter 2 (SGLT2) inhibitors were associated with twice the risk of diabetic ketoacidosis as dipeptidyl peptidase-4 (DPP4) inhibitors in patients with type 2 diabetes shortly after initiation of medication, although the overall risk was low, a recent study suggested.
Due to previous reports of an increased risk of diabetic ketoacidosis with SGLT2 inhibitors, the US FDA issued a warning in 2015.
Using a commercial claim database in the US, the researchers identified patients (mean age 54 years, 52.8 percent males) who had been newly prescribed with either an SGLT2 inhibitor (n=50,220) or a DPP4 inhibitor (n=90,132). [N Engl J Med 2017;376:2300-2302]
Within 180 days after medication initiation, hospitalization rate for diabetic ketoacidosis ─ the primary outcome ─ was twofold higher after initiating an SGLT2 inhibitor than a DPP4 inhibitor (4.9 vs 2.3 events per 1,000 person-years, unadjusted hazard ratio [HR], 2.1). The results remained similar after propensity-score matching for potential confounders (adjusted HR, 2.2, 95 percent confidence interval [CI], 1.4–3.6).
In sensitivity analyses, the risk of diabetic ketoacidosis with SGLT2 inhibitors remained at least twice that of initiating DPP4 inhibitors, regardless of whether it was within 30 days (HR, 2.3, 95 percent CI, 1.1–4.8) or 60 days of medication initiation (HR, 2.5, 95 percent CI, 1.3–4.7).
“DPP4 inhibitors were chosen as the comparator medication because they are similarly used as a second-line treatment for diabetes but have no known association with diabetic ketoacidosis,” according to study authors Drs Michael Fralick, Sebastian Schneeweiss, and Elisabetta Patorno from the Brigham and Women’s Hospital in Boston, Massachusetts, US.
Patients who received SGLT2 inhibitors were younger with fewer comorbidities than those treated with DPP4 inhibitors, but were also more likely to be on insulin.
After excluding patients receiving insulin in the analysis, the risk of diabetic ketoacidosis was still higher in patients receiving SGLT2 inhibitors than DPP4 inhibitors (HR, 2.5, 95 percent CI, 1.1–5.5).
“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,” advised Fralick and co-authors.