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

To evaluate the association between sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and the risk of neoplasm in patients with Type 2 diabetes (T2D). 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). 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%). 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. www.crd.york.ac.uk/prospero identifier is CRD42021273681. Type 2 diabetes (T2D) is a chronic metabolic disease that affects 1 in 10 people worldwide, and cancer is now recognized as a common and severe complication of T2D. Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are a class of novel anti-diabetic medications that benefit heart and kidney function. However, their influence on the risk of neoplasm (malignant or benign tumor) growth in T2D is still debatable. This paper presents the results of a meta-analysis of 53 randomized controlled trials, involving 126,232 participants, to assess the associations between the use of SGLT-2i and the risk of neoplasm in patients with T2D. It was found that SGLT-2i use was not associated with the risk of overall neoplasm in patients with T2D. However, the use of SGLT-2i seemed to be associated with a reduced risk of lung neoplasm but an increased risk of prostate neoplasm when compared with other anti-diabetic medications in patients with T2D. These findings suggest differences in SGLT-2i’s effects among different locations of neoplasm. This study might provide new insights for treating patients with T2D who are at high risk of developing neoplasm and inspire future investigations on the associations between SGLT-2i and these tumors. Further research is needed to validate these findings and explore the underlying mechanisms.