Background: Dapagliflozin reduces hyperglycaemia in patients with type 2 diabetes mellitus (T2DM) by increasing urinary glucose excretion.
Objectives: This study determined the overall safety profile of dapagliflozin in T2DM.
Methods: Safety of dapagliflozin in pooled analyses of phase IIb/III studies was evaluated. Patients received comparator or dapagliflozin as monotherapy, add-on to antidiabetic therapy, or as initial combination with metformin. Proportions of patients with adverse events (AEs) and prespecified parameters related to previous clinical observations and dapagliflozin's action were assessed. The principal analysis used data from 12 placebo-controlled studies. Rare events were assessed across phase IIb/III studies, including special populations, comparator-controlled trials and ongoing long-term extensions.
Results: In placebo-controlled studies, hypoglycaemia was more common with dapagliflozin (11.8 %) than placebo (7.0 %), with imbalance driven by add-on of dapagliflozin to sulfonylurea or insulin. Urinary tract infections (4.8 vs 3.7 %), vulvovaginitis/balanitis and related infections (5.1 vs 0.9 %), and non-serious volume-related events (0.8 vs 0.4 %) occurred more often with dapagliflozin than placebo. No substantial AEs were seen on electrolytes or renal function. Pyelonephritis was rare and balanced among treatments; there were no imbalances in fractures or liver test elevations. Overall incidence of malignancies was balanced between groups. The incidence rate ratios of malignancy in certain organ systems were slightly lower for dapagliflozin (renal tract, female reproductive) and in others were slightly lower for control (breast, prostate, bladder). Most AEs associated with dapagliflozin were mild/moderate and related to the mechanism of action.
Conclusion: Dapagliflozin has a favourable and predictable tolerability profile, with reported events related to its mechanism of action.