Investigating Risk of Cancer with Sodium-Glucose Cotransporter 2 Inhibitors: A Disproportionality Analysis in the WHO Global Pharmacovigilance Database Vigibase()

Drug Saf. 2025 Apr 15. doi: 10.1007/s40264-025-01546-5. Online ahead of print.

ABSTRACT

INTRODUCTION: Use of sodium-glucose cotransporter 2 inhibitors (SGLT-2is) has significantly increased due to their cardiovascular benefits. Whether SGLT-2is increase risk of cancer has been of concern since first clinical trials, but this question remains unclear because of methodological limitations in previous studies.

METHODS: We conducted a disproportionality analysis using Vigibase^® between 2014 and 2023 to estimate the association between SGLT-2i use and the risk of reporting of different subtypes of cancers, compared with glucagon like peptide-1 (GLP-1) analogues and dipeptidyl peptidase-4 (DPP-4) inhibitors.

RESULTS: Among 644 reported cases of cancer associated with SGLT-2i use, 427 (66.3%) were male, with a mean age of 66.5 ± 9.7 years. Sodium-glucose cotransporter 2 inhibitors showed increased reporting odds ratio for bladder cancer (ROR 4.46, 95% CI 3.23-6.17) and kidney cancer (ROR 1.84, 95% CI 1.25-2.69), but not for all other cancer subtypes.

CONCLUSION: In this disproportionality analysis with a hypothesis-generating approach, SGLT-2is are associated with an increased risk of reporting bladder and kidney cancer. There is a need of an urgent clarification of this signal with further long-term observational studies.

PMID:40232585 | DOI:10.1007/s40264-025-01546-5