SGLT2 inhibitors and risk of cancer in type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials
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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.
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.
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]).
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.
KeywordsCancer Meta-analysis Randomised controlled trials SGLT2 inhibitors Systematic review Type 2 diabetes
Cochrane Central Register of Controlled Trials
Randomised controlled trial
Sodium–glucose cotransporter 2
Surface under the cumulative ranking curve
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
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.
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.
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