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 which 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.

评估钠-葡萄糖协同转运蛋白2抑制剂（sodium-glucose cotransporter-2 inhibitors, SGLT-2i）与2型糖尿病（Type 2 diabetes, T2D）患者肿瘤发生风险的关联。检索自各数据库建库至2024年6月的文献，纳入比较SGLT-2i与安慰剂或其他治疗方案用于T2D患者且报告肿瘤事件的随机对照试验（randomized controlled trials, RCTs）。结果以风险比（risk ratio, RR）及95%置信区间（confidence intervals, CI）表示。共纳入53项RCT，涉及126,232名参与者。与未使用SGLT-2i的患者相比，使用SGLT-2i的患者总体肿瘤发生风险无显著差异（RR=1.08，95% CI：0.99至1.19，I²=23%）。然而，与未使用者相比，SGLT-2i使用者的肺部肿瘤发生风险降低（RR=0.83，95% CI：0.69至0.99，I²=0.0%），而前列腺肿瘤发生风险升高（RR=1.21，95% CI：1.00至1.47，I²=0.0%）。与未使用者相比，SGLT-2i的使用与总体肿瘤发生风险无关，但SGLT-2i使用者的肺部肿瘤发生率较低，而前列腺肿瘤发生风险较未使用者升高。英国约克大学CRD循证中心Prospero平台注册号为CRD42021273681（网址：www.crd.york.ac.uk/prospero）。2型糖尿病（T2D）是一种慢性代谢性疾病，全球每10人中即有1人受其影响，而癌症目前已被认为是T2D常见且严重的并发症之一。钠-葡萄糖协同转运蛋白2抑制剂（SGLT-2i）是一类新型抗糖尿病药物，对心肾功能具有保护作用。然而，其对T2D患者肿瘤（恶性或良性）发生风险的影响仍存在争议。本文报告了一项纳入53项随机对照试验（涉及126,232名参与者）的meta分析结果，旨在评估SGLT-2i使用与T2D患者肿瘤发生风险的关联。研究发现，SGLT-2i的使用与T2D患者总体肿瘤发生风险无关，但与其他抗糖尿病药物相比，SGLT-2i的使用似乎与T2D患者肺部肿瘤发生风险降低、前列腺肿瘤发生风险升高相关。这些发现提示SGLT-2i对不同部位肿瘤的影响存在差异。本研究或可为T2D合并高肿瘤风险患者的治疗提供新的思路，并为未来探索SGLT-2i与这些肿瘤的关联提供启发。需进一步研究验证这些发现并探索其潜在机制。