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Diabetes Obes Metab. 2018 Mar;20(3):620-628. doi: 10.1111/dom.13124. Epub 2017 Oct 26.

Dapagliflozin in patients with type 2 diabetes mellitus: A pooled analysis of safety data from phase IIb/III clinical trials.

Author information

1
Department of Endocrinology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania.
2
Division of Endocrinology and Diabetology, Department of Internal Medicine II, University Hospital of Freiburg, Medical Faculty, University of Freiburg, Freiburg, Germany.
3
Department of Medicine, University of Liège, Liège, Belgium.
4
School of Life and Health Sciences, Aston University, Birmingham, UK.
5
Department of AZ Global Regulatory Affairs, Patient Safety and QA (GRAPSQA), AstraZeneca Gothenburg, Mölndal, Sweden.
6
Department of R&D, AstraZeneca Gothenburg, Mölndal, Sweden.

Abstract

AIM:

To evaluate the safety and tolerability of dapagliflozin, a highly selective sodium-glucose co-transporter-2 inhibitor, in patients with type 2 diabetes mellitus (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 weeks; dapagliflozin, n = 5936; control, n = 3403) and 30 trials (≥12 weeks; 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 similar for dapagliflozin and placebo: 60.0% vs 55.7% and 5.1% vs 5.4%, respectively. Rates of hypoglycaemia, volume depletion AEs, urinary tract infections (UTIs) and fractures were balanced between the groups. Genital infections were more frequent with dapagliflozin (5.5%) vs placebo (0.6%) and renal function AEs occurred in 3.2% vs 1.8% of patients (the most common renal AE was decreased creatinine clearance: 1.1% vs 0.7%). In the 21-study pool, 1 SAE of DKA and 3 AEs of ketonuria/metabolic acidosis occurred with dapagliflozin vs none with control; estimated combined incidence for these events was 0.03% (95% confidence interval 0.010-0.089). In the 30-study pool, lower limb amputation occurred in 8 (0.1%) and 7 (0.2%) patients receiving dapagliflozin and control, respectively.

CONCLUSION:

The overall incidence rates of AEs and SAEs were similar in the dapagliflozin and placebo/control groups, including the incidence of hypoglycaemia, volume depletion, fractures, UTIs, amputations and DKA. Genital infections were more frequent with dapagliflozin than placebo.

KEYWORDS:

SGLT2 inhibitor; antidiabetic drug; dapagliflozin; type 2 diabetes

PMID:
28950419
PMCID:
PMC5836959
DOI:
10.1111/dom.13124
[Indexed for MEDLINE]
Free PMC Article

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