Highlights
- •Data on malignancy risk with SGLT2 inhibitors is conflicting.
- •The effect of SGLT2 inhibitors on cancer mortality is unknown.
- •Meta-analysis to evaluate cancer outcomes with SGLT2 inhibitor treatment in adults.
- •Pooled data of 116,365 participants showed no increse in risk of cancer outcomes.
- •TSA showed that the sample size was sufficient to avoid missing alternative results.
Abstract
Aims
Concerns regarding breast and bladder cancer risk with Sodium-glucose cotransporter-2
(SGLT2) inhibitors remain controversial and its effect on cancer mortality is unknown.
We aim to evaluate the association between SGLT2 inhibitors and the risk of cancer
outcomes.
Methods
We searched PubMed, Embase and CENTRAL up to June 20th, 2022, for randomized controlled
trials of SGLT2 inhibitors in adults, with a minimum follow-up of 48 weeks. Researchers
extracted study-level data and assessed within-study risk of bias with the RoB 2.0
tool and quality of evidence with GRADE. We performed meta-analyses summarizing the
relative risks (RRs) of cancer outcomes.
Results
Seventy-six trials encompassing 116,375 participants were selected. Overall risk of
bias was low. SGLT2 inhibitors did not reduce/increase the overall risk of cancer
(RR, 1.03; 95% confidence interval [CI], 0.96–1.10) and cancer mortality (RR, 0.99;
95% CI, 0.85–1.16). SGLT2 inhibitors likely result in little to no difference in the
risk of breast (RR, 1.01; 95% CI 0.77–1.32) and bladder cancers (RR, 0.93; 95% CI
0.71–1.21). Trial sequential analysis provided evidence that the sample size was sufficient
to avoid missing alternative results.
Conclusions
SGLT2 inhibitors are not associated with an increased risk of cancer outcomes, providing
reassuring data regarding previous safety concerns.
Keywords
Abbreviations:
BMI (body mass index), CI (Confidence interval), DOI (Digital Object Identifier), FDA (Food and Drug Administration), GRADE (Grading of Recommendations, Assessment, Development and Evaluations), NNH (Number needed to harm), PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), RCTs (randomized controlled trials), RD (Risk difference), RoB 2 (Revised Cochrane risk-of-bias tool for randomized trials), robvis (Risk-of-bias VISualization), RR (relative risk), SGLT2 (Sodium-glucose cotransporter-2), TSA (Trial Sequential Analysis)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: March 12, 2023
Accepted:
March 7,
2023
Received in revised form:
February 21,
2023
Received:
February 2,
2023
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 Published by Elsevier B.V.
