Revisiting the association between sodium-glucose cotransporter-2 inhibitors and the risk of neoplasm in patients with type 2 diabetes: new insights from an updated systematic review and meta-analysis of randomized controlled trials

Objective: To evaluate the association between sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and the risk of neoplasm in patients with Type 2 diabetes (T2D). Methods: Literature retrieval was conducted using databases from inception to June 2024. Randomized controlled trials (RCTs) comparing SGLT-2i with placebo or other treatments in patients with T2D, and with reports of neoplasm events were included. Results were computed as the risk ratio (RR) with 95% confidence intervals (CI). Results: A total of 53 RCTs with 126,232 participants were included. No significant differences were found for the risk of overall neoplasm (RR = 1.08, 95% CI: 0.99 to 1.19, I² = 23%) in patients with SGLT-2i treatment compared with non-users. However, decreased risk of pulmonary neoplasm (RR = 0.83, 95% CI: 0.69 to 0.99, I² = 0.0%) was observed in SGLT-2i users compared to non-users, while increased risk of prostate neoplasm in SGLT-2i users was found (RR = 1.21, 95% CI: 1.00 to 1.47, I² = 0.0%). Conclusion: Compared with non-users, the use of SGLT-2i was not associated with the risk of overall neoplasm. However, pulmonary neoplasms were less frequent in SGLT-2i users, while an increased risk of prostate neoplasm was observed in SGLT-2i users compared to non-users. Protocol registration: www.crd.york.ac.uk/prospero identifier is CRD42021273681.