Dapagliflozin reduces hyperglycaemia in patients with type 2 diabetes mellitus (T2DM) by increasing urinary glucose excretion.
This study determined the overall safety profile of dapagliflozin in T2DM.
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.
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.
Dapagliflozin has a favourable and predictable tolerability profile, with reported events related to its mechanism of action.
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This study was supported by AstraZeneca and Bristol-Myers Squibb. The sponsors were involved in the design and conduct of the study; collection, management, analysis and interpretation of the data; and preparation, review and approval of the manuscript. Medical writing and editorial assistance was provided by Alexandra Silveira, PhD, of PPSI (a PAREXEL company) and funded by AstraZeneca and Bristol-Myers Squibb. Parts of this study were presented in abstract form at the 72nd Scientific Sessions of the American Diabetes Association, Philadelphia, Pennsylvania, 8–12 June 2012 and at the 48th Annual Meeting of the European Association for the Study of Diabetes, Berlin, Germany, 1–5 October 2012. Agata Ptaszynska supervised the study, analysed and interpreted data and wrote and revised the article. James F. List, Kristina M. Johnsson, Shamik J. Parikh and Tjerk W.A. de Bruin contributed to the study concept and design, analyzed and interpreted data and wrote and revised the article. Anne Marie Apanovitch contributed to the study concept and design, contributed to statistical verification of data, analyzed and interpreted data and wrote and revised the article.
Conflict of interest
Agata Ptaszynska, Anne Marie Apanovitch. and James F. List. are employees and shareholders of Bristol-Myers Squibb. Kristina M. Johnsson is an employee of AstraZeneca. Shamik J. Parikh and Tjerk W.A. de Bruin are employees and shareholders of AstraZeneca.
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Ptaszynska, A., Johnsson, K.M., Parikh, S.J. et al. Safety Profile of Dapagliflozin for Type 2 Diabetes: Pooled Analysis of Clinical Studies for Overall Safety and Rare Events. Drug Saf 37, 815–829 (2014). https://doi.org/10.1007/s40264-014-0213-4
- Placebo Group
- Uric Acid Level
- Urinary Stone