Safety of dapagliflozin in a broad population of patients with type 2 diabetes: Analyses from the DECLARE‐TIMI 58 study

Abstract

Aims To comprehensively evaluate the safety of dapagliflozin in patients with type 2 diabetes (T2DM) with emphasis placed on potential safety concerns related to the SGLT2‐inhibitors class. Methods In DECLARE‐TIMI 58, 17,160 patients with T2DM were randomized to dapagliflozin or placebo and followed for a median of 4.2 years. Safety was evaluated in 17,143 patients receiving at least one dose of study drug. Results Acute kidney injury occurred less frequently with dapagliflozin, and adverse events suggestive of volume depletion were balanced between treatment groups, both irrespective of baseline eGFR, blood pressure, diuretic or loop diuretic use (interaction‐p‐values >0.05). Fractures and malignancies were balanced irrespective of sex, diabetes duration or smoking (interaction p‐values >0.05) and fewer cases of bladder cancer occurred in the dapagliflozin vs. placebo group. Diabetic ketoacidosis (DKA) was very rare, but more frequent with dapagliflozin vs. placebo (27 vs. 12 patients with events; p=0.02), yet signs, symptoms and contributing factors were similar in both groups. Major hypoglycemia occurred less frequently with dapagliflozin vs. placebo regardless of baseline use of either insulin or sulfonylureas (interaction p‐values >0.05). There were more adverse events of genital infections leading to discontinuation of study drug in the dapagliflozin vs. placebo group, but serious genital infections were few and balanced between treatment groups. Urinary tract infections, acute pyelonephritis and urosepsis were also balanced between treatment groups. Conclusions Dapagliflozin was well tolerated. The long duration and large number of patient‐years in DECLARE‐TIMI 58 comprehensively addressed previous safety questions, confirming the robust safety profile of dapagliflozin.