Cancer related safety with SGLT2-i and GLP1-RAs: Should we worry?

SGLT2 inhibitors (SGLT2i) have lately gained popularity as an effective treatment for type 2 diabetes (T2D), with additional benefits due to well-known large trials showing cardiovascular and kidney protection, especially in patients with established chronic kidney disease and heart failure. While SGLT2i have been shown to be effective for treating T2D, there have been concerns about their potential risks, including the risk of cancer. Some studies showed an increased risk of cancer [ [1] Shi N. Shi Y. Xu J. Si Y. Yang T. Zhang M. et al. SGLT-2i and Risk of Malignancy in Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials. Front Public Health. 2021; : 9https://doi.org/10.3389/fpubh.2021.668368 Crossref Scopus (8) Google Scholar ], especially for bladder cancer [ [2] García M. Arteche-Martinez U. Lertxundi U. Aguirre C. SGLT2 Inhibitors and Bladder Cancer: Analysis of Cases Reported in the European Pharmacovigilance Database. The Journal of Clinical Pharmacology. 2021; 61: 187-192https://doi.org/10.1002/jcph.1722 Crossref PubMed Scopus (15) Google Scholar ], whereas some others did not find any connection [ 3 Tang H. Dai Q. Shi W. Zhai S. Song Y. Han J. SGLT2 inhibitors and risk of cancer in type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials. Diabetologia. 2017; 60: 1862-1872https://doi.org/10.1007/s00125-017-4370-8 Crossref PubMed Scopus (103) Google Scholar , 4 Tang H. Yang K. Song Y. Han J. Meta-analysis of the association between sodium-glucose co-transporter-2 inhibitors and risk of skin cancer among patients with type 2 diabetes. Diabetes Obes Metab. 2018; 20: 2919-2924https://doi.org/10.1111/dom.13474 Crossref PubMed Scopus (6) Google Scholar , 5 Dicembrini I. Nreu B. Mannucci E. Monami M. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors and cancer: A meta-analysis of randomized controlled trials. DiabetesObes Metab. 2019; 21: 1871-1877https://doi.org/10.1111/dom.13745 Crossref Scopus (38) Google Scholar , 6 Pelletier R. Ng K. Alkabbani W. Labib Y. Mourad N. Gamble J. The association of sodium-glucose cotransporter 2 inhibitors with cancer: An overview of quantitative systematic reviews. Endocrinol DiabetesMetab. 2020;; : 3https://doi.org/10.1002/edm2.145 Crossref Scopus (12) Google Scholar , 7 Abrahami D. Tesfaye H. Yin H. Vine S. Hicks B. Yu O.H.Y. et al. Sodium-Glucose Cotransporter 2 Inhibitors and the Short-term Risk of Bladder Cancer: An International Multisite Cohort Study. Diabetes Care. 2022; 45: 2907-2917https://doi.org/10.2337/dc22-1174 Crossref PubMed Scopus (3) Google Scholar ].