Systematic Reviews/Meta-Analysis
Sunday, November 12, 2023
12:45 PM–02:15 PM
Abstract
Background: Previous randomized controlled trials of sodium-glucose cotransporter 2 (SGLT-2) inhibitors have reported a numerical imbalance of bladder cancer events among patients randomized to dapagliflozin and empagliflozin. However, it remains unclear whether the imbalance is a result of chance or is related to the carcinogenic effects of these medications. To assess the risk of bladder cancer among patients using SGLT-2 inhibitors, we conducted a systematic review of observational studies.
Methods: We screened PubMed and Embase up until May 2023 using the keywords ‘SGLT-2 inhibitors’ and ‘bladder cancer’. Studies were eligible if they are observational studies that investigated the risk of bladder cancer among patients with SGLT-2 inhibitors, regardless of the comparator drug. We used the Joanna Briggs Institute critical appraisal checklists to evaluate the methodological quality of each study.
Results: We included two cross-sectional studies and three retrospective cohort studies, involving a total of 41,512,603 patients. The cross-sectional studies, conducted using nationwide pharmacovigilance databases, employed disproportionality analysis. Both studies identified a disproportionately high number of bladder cancer cases among SGLT-2 inhibitors users compared to non-users, suggesting a safety signal. Conversely, the cohort studies, which compared SGLT-2 inhibitors with dipeptidyl peptidase 4 inhibitors, glucagon-like peptide-1 receptor agonists or other anti-diabetic drugs, found no significant increase in the risk of bladder cancer. Importantly, these studies had a median follow-up range of 1.5 to 3 years. All studies were rated as good quality.
Discussion: The disproportionality signal identified from the pharmacovigilance databases is useful in generating safety signal but cannot establish causality. Consistent with a recent meta-analysis of randomized-controlled trials, our included cohort studies did not show an increased risk of bladder cancer associated with SGLT-2 inhibitors. However, the follow-up period of three years was insufficient to evaluate potential carcinogenic effects. Further studies with longer follow-up periods are warranted.
Other: Funding: None. Conflicts of interest: None. Registration: None.
Presenting Author
Pony Yee Chee Chai MScKeelung Chang Gung Memorial Hospital
Authors
Chian-Ting Chang MSc
Chang gung memorial hospital, Keelung, Taiwan
Yi-Hua Chen MSc
Keelung Chang Gung Memorial Hospital
Yung-Chih Chen MD
Chang gung memorial hospital, Keelung, Taiwan