Safety evaluation of Sodium-glucose cotransporter 2 inhibitors for cancer risk in specific populations: systematic review and meta-analysis.

Abstract

Aims: Sodium-glucose cotransporter 2 (SGLT2) inhibitors, commonly treated for Type 2 diabetes mellitus (T2DM), have demonstrated benefits in reducing cardiovascular and renal events. However, heart failure (HF) and chronic kidney disease (CKD) are prevalent comorbidities in T2DM. This study aims to assess the long-term safety of SGLT2 inhibitor, particularly concerning cancer risk in these populations.

Methods: We searched PubMed, CENTRAL, Web of Science, and ClinicalTrials.gov for studies published up to April 16, 2024. The primary outcome was overall cancer risk, with secondary outcomes focused on specific cancer types. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated. This meta-analysis was registered in PROSPERO (CRD42024560310).

Results: 28 randomized controlled trials involving 98,297 participants were included. SGLT2 inhibitors did not increase overall cancer risk (RR = 1.05, 95% CI [0.99, 1.12]). Furthermore, the use of SGLT2 inhibitors does not exhibit a significant association with the risk of several common cancer types. Subgroup analyzes indicated that SGLT2 inhibitors appeared to be temporarily safe in patients with HF (RR = 1.03, 95% CI [0.91, 1.18]), CKD (RR = 1.02, 95% CI [0.90, 1.16]) and T2DM related comorbidities. Additionally, none of the different types of SGLT2 inhibitors increase the overall cancer risk.

Conclusions: SGLT2 inhibitors do not appear to increase overall cancer risk, including several common cancers such as breast cancer and bladder cancer. The use of SGLT2 inhibitors in different patient populations is temporarily safe.

Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024560310.