Diabetologia

, Volume 60, Issue 10, pp 1862–1872 | Cite as

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

Article

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.

Keywords

Cancer Meta-analysis Randomised controlled trials SGLT2 inhibitors Systematic review Type 2 diabetes 

Abbreviations

CENTRAL

Cochrane Central Register of Controlled Trials

RCT

Randomised controlled trial

SGLT2

Sodium–glucose cotransporter 2

SUCRA

Surface under the cumulative ranking curve

Notes

Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Funding

The project described was supported by the Indiana University Health–Indiana University School of Medicine Strategic Research Initiative.

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Contribution statement

HT, YS and JH designed the study. HT and WS identified and acquired reports of trials and extracted data. HT, QD, WS, SZ, YS and JH performed all data analyses, checked for statistical inconsistency, and interpreted data. HT, QD, WS, SZ, YS and JH contributed to data interpretation. HT drafted the report and all other authors critically reviewed the report. All authors approved the final version of manuscript. JH is the guarantor of this work.

Supplementary material

125_2017_4370_MOESM1_ESM.pdf (1.6 mb)
ESM(PDF 1615 kb)

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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Department of PharmacyPeking University Third HospitalBeijingPeople’s Republic of China
  2. 2.Department of Epidemiology, Richard M. Fairbanks School of Public HealthIndiana UniversityIndianapolisUSA
  3. 3.Center for Pharmacoepidemiology, Richard M. Fairbanks School of Public HealthIndiana UniversityIndianapolisUSA
  4. 4.Department of Medicine, School of Medicine, Vanderbilt Ingram Cancer Center, Vanderbilt University Medical CenterVanderbilt UniversityNashvilleUSA
  5. 5.Melvin and Bren Simon Cancer CenterIndiana UniversityIndianapolisUSA

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