(HealthDay News) — In patients with type 2 diabetes, sodium-glucose cotransporter-2 (SGLT-2) inhibitors are associated with an increased risk for diabetic ketoacidosis (DKA), according to a study published online in the Annals of Internal Medicine.

Antonios Douros, MD, PhD, from McGill University in Montreal, and colleagues matched 208,757 new users of SGLT-2 inhibitors with 208,757 recipients of dipeptidyl peptidase-4 (DPP-4) inhibitors to compare the risk for DKA in patients with type 2 diabetes. Data were obtained from seven Canadian provinces and the United Kingdom.

The researchers found that during 370,454 person-years of follow-up, 521 patients were diagnosed with DKA (incidence rate, 1.40 per 1000 person-years). The risk for DKA was increased in association with SGLT-2 inhibitors versus DPP-4 inhibitors (incidence rate, 2.03 vs 0.75; hazard ratio, 2.85). Molecule-specific hazard ratios were 1.86, 2.52, and 3.58 for dapagliflozin, empagliflozin, and canagliflozin, respectively. The association was not modified by age or sex; prior insulin receipt seemed to reduce the risk.

“Because the beneficial effects of SGLT-2 inhibitors in the prevention of cardiovascular and renal disease will probably increase their uptake in the following years, physicians should be aware of DKA as a potential adverse effect,” the authors write.

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Douros A, Lix LM, Fralick M, et al. Sodium–Glucose Cotransporter-2 Inhibitors and the Risk for Diabetic Ketoacidosis: A Multicenter Cohort Study. Ann Intern Med. doi: 10.7326/M20-0289