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Hypersensitivity Events, Including Potentially Hypersensitivity-Related Skin Events, with Dapagliflozin in Patients with Type 2 Diabetes Mellitus: A Pooled Analysis

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Abstract

Background

In patients with type 2 diabetes mellitus (T2DM), dapagliflozin improves glycemic control and has a safety profile typically related to its mechanism of action. Hypersensitivity adverse events (AEs) have been reported in some patients with sodium-glucose cotransporter 2 (SGLT2) inhibitors, including a recent report of dermatological AEs in Japan.

Methods

We investigated the frequency and characteristics of hypersensitivity AEs, including potentially hypersensitivity-related skin AEs, across 21 phase IIb/III trials of dapagliflozin (N = 5936) versus active or placebo comparators (N = 3403), including the subpopulation of Asian patients (N = 1563).

Results

Overall, AEs and serious AEs (SAEs) of hypersensitivity were infrequent and were reported in a similar proportion of patients with dapagliflozin versus active or placebo comparators (AEs: 4.5 vs. 4.3 %; SAEs: 0.2 vs. 0.1 %, respectively). The most common events affected the skin or subcutaneous tissue: rash (dapagliflozin: 1.1 %, comparator: 1.1 %), eczema (0.6, 0.8 %), dermatitis (0.5, 0.4 %), and urticaria (0.5, 0.2 %). Few patients discontinued as a result of hypersensitivity AEs (≤0.2 %). In patients of Asian descent, a lower frequency of hypersensitivity AEs was observed with dapagliflozin versus comparators (2.0 vs. 4.5 %). In the subset of placebo-controlled trials, hypersensitivity AEs were slightly more frequent with dapagliflozin than with placebo across the overall population (4.7 vs. 3.8 %), and less frequent with dapagliflozin in Asian patients (1.5 vs. 5.0 %).

Conclusions

The findings of this post hoc analysis indicate that dapagliflozin does not lead to an increased risk of serious hypersensitivity reactions or potentially hypersensitivity-related skin events among patients with T2DM, including Asian patients. Long-term outcome studies and postmarketing surveillance will provide further information on hypersensitivity reactions with SGLT2 inhibitors.

ClinicalTrials.gov Identifiers

NCT01042977, NCT01031680, NCT00855166, NCT00984867, NCT01294423, NCT00673231, NCT00972244, NCT00680745, NCT00660907, NCT01095653, NCT00831779, NCT00976495, NCT00859898, NCT00736879, NCT00683878, NCT00663260, NCT00643851, NCT00528879, NCT00528372, NCT00357370, NCT00263276

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Acknowledgments

The authors would like to acknowledge statistical analysis support provided by Jennifer Sugg, a former employee of AstraZeneca, Daniel Reyner of AstraZeneca, and Valerie Cain of Bogier Consulting, Inc.

These data were previously presented at the 75th Scientific Sessions of the American Diabetes Association (ADA), Boston, MA, USA, 5–9 June 2015, and at the 51st Annual Meeting of the European Association for the Study of Diabetes (EASD), Stockholm, Sweden, 14–18 September 2015.

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Authors and Affiliations

  1. AstraZeneca Gothenburg, Patient Safety, Pepparredsleden 1, 43150, Mölndal, Sweden

    Annika Mellander, Martin Billger, Eva Johnsson, Anna Karin Träff & Kristina Johnsson

  2. AstraZeneca, Osaka, Japan

    Shigeru Yoshida

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  1. Annika Mellander
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  2. Martin Billger
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Corresponding author

Correspondence to Annika Mellander.

Ethics declarations

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval of the version to be published.

Funding

This study was funded by AstraZeneca. Writing support was provided by Safeer Mughal, PhD, Robert Axford-Gatley, MD, and Jean Turner of PAREXEL International, and was funded by AstraZeneca.

Conflict of interest

Annika Mellander, Martin Billger, Eva Johnsson, Anna Karin Träff, and Kristina Johnsson are employees/stockholders of AstraZeneca Gothenburg, Mölndal, Sweden. Shigeru Yoshida is an employee of AstraZeneca, Japan.

Ethical approval

This article is based on previously conducted studies, and does not involve any new studies of human or animal subjects performed by any of the authors.

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Mellander, A., Billger, M., Johnsson, E. et al. Hypersensitivity Events, Including Potentially Hypersensitivity-Related Skin Events, with Dapagliflozin in Patients with Type 2 Diabetes Mellitus: A Pooled Analysis. Clin Drug Investig 36, 925–933 (2016). https://doi.org/10.1007/s40261-016-0438-3

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