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Diabetologia
Published in: Diabetologia 10/2017

01-10-2017 | Article

SGLT2 inhibitors and risk of cancer in type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials

Authors: Huilin Tang, Qi Dai, Weilong Shi, Suodi Zhai, Yiqing Song, Jiali Han

Published in: Diabetologia | Issue 10/2017

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Abstract

Aims/hypothesis

The association between sodium–glucose cotransporter 2 (SGLT2) inhibitors and the risk of cancer in individuals with type 2 diabetes remains uncertain. This study aimed to evaluate the risk of cancer associated with SGLT2 inhibitor treatment of type 2 diabetes.

Methods

We systematically searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials and ClinicalTrials.​gov from inception to 15 February 2017 to identify eligible randomised controlled trials (RCTs) that report cancer events in individuals with type 2 diabetes treated with SGLT2 inhibitors for at least 24 weeks. We performed pairwise and network meta-analyses as well as a cumulative meta-analysis to calculate ORs and 95% CIs.

Results

In total, 580 incidences of cancer among 34,569 individuals were identified from 46 independent RCTs with a mean trial duration of 61 weeks. When compared with comparators (placebo or other active glucose-lowering treatments), SGLT2 inhibitors were not significantly associated with an increased risk of overall cancer (OR 1.14 [95% CI 0.96, 1.36]). For pre-specified cancer types, the risk of bladder cancer might be increased with SGLT2 inhibitors (OR 3.87 [95% CI 1.48, 10.08]), especially empagliflozin (OR 4.49 [95% CI 1.21, 16.73]). Interestingly, canagliflozin might be protective against gastrointestinal cancers (OR 0.15 [95% CI 0.04, 0.60]).

Conclusions/interpretation

Current evidence from short-term RCTs did not indicate a significantly increased risk of overall cancer among individuals with type 2 diabetes using SGLT2 inhibitors. Given the short-term trial durations and uncertainty of evidence, future long-term prospective studies and post-marketing surveillance studies are warranted.
Appendix
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Metadata
Title
SGLT2 inhibitors and risk of cancer in type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials
Authors
Huilin Tang
Qi Dai
Weilong Shi
Suodi Zhai
Yiqing Song
Jiali Han
Publication date
01-10-2017
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 10/2017
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-017-4370-8

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