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Dapagliflozin in patients with type 2 diabetes mellitus: a pooled analysis of safety data from Phase 2b/3 clinical trials
Aim
Dapagliflozin is a highly selective sodium–glucose cotransporter-2 inhibitor for the treatment of type 2 diabetes mellitus (T2DM). This pooled analysis evaluated the safety and tolerability of dapagliflozin in patients with T2DM.
Methods
Data were pooled from 13 placebo-controlled trials of up to 24 weeks’ duration (dapagliflozin, n=2360; placebo, n=2295). Larger placebo/comparator-controlled pools of 21 (≤208 week; dapagliflozin, n=5936; control, n=3403) and 30 trials (≥12 week; dapagliflozin, n=9195; control, n=4629) assessed the rare adverse events (AEs) of diabetic ketoacidosis (DKA) and lower-limb amputation, respectively.
Results
Over 24 weeks, the overall incidence of AEs and serious AEs (SAEs) was comparable for dapagliflozin and placebo; 60.0% versus 55.7% and 5.1% versus 5.4%, respectively. Rates of hypoglycemia, volume depletion AEs, urinary tract infections (UTIs) and fractures were balanced between groups. Genital infections were more frequent with dapagliflozin (5.5%) versus placebo (0.6%) and renal function AEs occurred in 3.2% versus 1.8% of patients (most common renal AE was decreased creatinine clearance: 1.1% versus 0.7%). In the 21-study pool, one SAE of DKA and three AEs of ketonuria/metabolic acidosis occurred with dapagliflozin versus none with control; estimated combined incidence for these events was 0.03% (95% CI:0.010–0.089). In the 30-study pool, lower-limb amputation occurred in eight (0.1%) and seven (0.2%) patients receiving dapagliflozin and control, respectively.
Conclusion
The overall incidence of AEs and SAEs was comparable in the dapagliflozin and placebo/control groups, including the incidence of hypoglycemia, volume depletion, fractures, UTIs, amputations and DKA. Genital infections were more frequent with dapagliflozin than placebo.
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