Sodium-glucose cotransporter-2 inhibitor treatment has differential effects on the incidence of various malignancies: Evidence from a spontaneous adverse reaction database

Int J Clin Pharmacol Ther. 2025 Mar;63(3):98-104. doi: 10.5414/CP204645.

Abstract

Objective: Sodium-glucose cotransporter (SGLT) 2 inhibitors are expected to demonstrate secondary effects against malignancy. However, long-term and large-scale data are required to evaluate the effects of SGLT2 inhibitors on malignancy, which has not been sufficiently studied in clinical practice. This study aimed to evaluate the association between SGLT2 inhibitors and malignancy using the spontaneous adverse reaction database.

Materials and methods: The United States Food and Drug Administration Adverse Event Reporting System database between 1997 (4Q) and 2020 (2Q) was used in this study. Reporting odds ratio (ROR) was selected as the safety-signaling measure. An inverse signal suggesting potential alternative therapeutic opportunities was defined when the upper limit of 95% confidence interval (CI) was < 1. The association between SGLT2 inhibitors and malignancies was evaluated.

Results: The total number of reports in the database during the study period was 13,106,455. SGLT2 inhibitors showed significant associations with pancreatic cancer (ROR: 3.08. 95% CI: 2.68 - 3.55), and kidney cancer (ROR: 1.39. 95% CI: 1.13 - 1.72). SGLT2 inhibitors showed significant inverse associations with breast cancer (ROR: 0.32. 95% CI: 0.27 - 0.39), lung cancer (ROR: 0.47. 95% CI: 0.37 - 0.59), liver cancer (ROR: 0.68. 95% CI: 0.50 - 0.93), and malignant melanoma (ROR: 0.49. 95% CI: 0.34 - 0.70).

Conclusion: SGLT2 inhibitors may increase the incidence of pancreatic cancer and kidney cancer, and decrease the incidence of breast cancer, lung cancer, liver cancer, and malignant melanoma. These associations need to be further examined in other clinical studies and research in the future.

MeSH terms

  • Adult
  • Adverse Drug Reaction Reporting Systems* / statistics & numerical data
  • Aged
  • Databases, Factual*
  • Female
  • Humans
  • Incidence
  • Kidney Neoplasms / chemically induced
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / epidemiology
  • Male
  • Middle Aged
  • Neoplasms* / chemically induced
  • Neoplasms* / drug therapy
  • Neoplasms* / epidemiology
  • Pancreatic Neoplasms / chemically induced
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / epidemiology
  • Risk Factors
  • Sodium-Glucose Transporter 2 Inhibitors* / adverse effects
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use
  • United States / epidemiology
  • United States Food and Drug Administration

Substances

  • Sodium-Glucose Transporter 2 Inhibitors