Abstract：
OBJECTIVE: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1ra) reduce cardiovascular events through different mechanisms, but their association with cancer remains unclear. The aim of this study was to compare the effect of combined treatment (SGLT2i and GLP1ra) and monotherapy (SGLT2i or GLP1ra) on hospitalization and/or death from cancer in a general population and a subgroup of patients with cardiovascular disease (CVD).
METHODS: We conducted a nonconcurrent observational prospective study of patients prescribed SGLT2i, GLP1ra, or both. Multinomial propensity scores were performed in the entire population and in a subgroup of patients with CVD. A multivariate Cox regression analysis was used to determine the hazard ratio (HR) for age, sex, risk factors, and treatment for each outcome.
RESULTS: We included 14 709 patients (11366 with SGLT2i, 1016 with GLP1ra, and 2327 with both treatments) from treatment initiation. Diabetes was present in 97% of the patients. The subgroup with CVD included 4957 (33.7%) patients. After a median of 33 months of follow-up, the risk of adverse cancer events was similar between patients with and without CVD (3.4% or 3.7%, respectively). The main risk factors for cancer mortality were male sex and age. Combined treatment and its duration reduced the risk of cancer mortality compared with monotherapy with SGLT2i or GLP1ra in the overall population (HR, 0.2216; 95%CI, 0.1106-0.4659; P<.001; and HR, 0.1928; 95%CI, 0.071-0.5219; P=.001, respectively) and in the subgroup of patients with CVD (HR, 0.2879; 95%CI, 0.0878-0.994; P<.049; and HR, 0.1329; 95%CI, 0.024-0.6768; P=.014, respectively).
CONCLUSIONS: Initiation of combined therapy (SGLT2i and GLP1ra) vs monotherapy with SGLT2i or GLP1ra was associated with a lower risk of cancer mortality, mostly in diabetic patients with or without CVD. Although clinical trials are needed, these results might be explained by the complementary mechanisms of these drugs, including their antiproliferative, anti-inflammatory, and metabolic effects. Future clinical trials and mechanistic studies will clarify the possible role of these drugs in carcinogenesis.
METHODS: We conducted a nonconcurrent observational prospective study of patients prescribed SGLT2i, GLP1ra, or both. Multinomial propensity scores were performed in the entire population and in a subgroup of patients with CVD. A multivariate Cox regression analysis was used to determine the hazard ratio (HR) for age, sex, risk factors, and treatment for each outcome.
RESULTS: We included 14 709 patients (11366 with SGLT2i, 1016 with GLP1ra, and 2327 with both treatments) from treatment initiation. Diabetes was present in 97% of the patients. The subgroup with CVD included 4957 (33.7%) patients. After a median of 33 months of follow-up, the risk of adverse cancer events was similar between patients with and without CVD (3.4% or 3.7%, respectively). The main risk factors for cancer mortality were male sex and age. Combined treatment and its duration reduced the risk of cancer mortality compared with monotherapy with SGLT2i or GLP1ra in the overall population (HR, 0.2216; 95%CI, 0.1106-0.4659; P<.001; and HR, 0.1928; 95%CI, 0.071-0.5219; P=.001, respectively) and in the subgroup of patients with CVD (HR, 0.2879; 95%CI, 0.0878-0.994; P<.049; and HR, 0.1329; 95%CI, 0.024-0.6768; P=.014, respectively).
CONCLUSIONS: Initiation of combined therapy (SGLT2i and GLP1ra) vs monotherapy with SGLT2i or GLP1ra was associated with a lower risk of cancer mortality, mostly in diabetic patients with or without CVD. Although clinical trials are needed, these results might be explained by the complementary mechanisms of these drugs, including their antiproliferative, anti-inflammatory, and metabolic effects. Future clinical trials and mechanistic studies will clarify the possible role of these drugs in carcinogenesis.
摘要：
目的：钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）和胰高血糖素样肽-1受体激动剂（GLP1ra）通过不同的机制减少心血管事件，但它们与癌症的关系尚不清楚。这项研究的目的是比较联合治疗（SGLT2i和GLP1ra）和单药治疗（SGLT2i或GLP1ra）对普通人群和心血管疾病（CVD）患者亚组中癌症住院和/或死亡的影响。
方法：我们对服用SGLT2i的患者进行了一项非并发观察性前瞻性研究，GLP1ra,或者两者兼而有之。在整个人群和CVD患者亚组中进行多项倾向评分。多变量Cox回归分析用于确定年龄的风险比(HR)，性别,危险因素，以及对每个结果的治疗。
结果：我们纳入了14709例患者（11366例SGLT2i，1016与GLP1ra，和2327两种治疗）从治疗开始。97%的患者出现糖尿病。CVD亚组包括4957例(33.7%)患者。在中位随访33个月后，有和无CVD患者的不良癌症事件风险相似(3.4%或3.7%,分别)。癌症死亡的主要危险因素是男性性别和年龄。与SGLT2i或GLP1ra的单药治疗相比，在总体人群中，联合治疗及其持续时间降低了癌症死亡率的风险（HR，0.2216；95CI，0.1106-0.4659；P<.001；和HR，0.1928；95CI，0.071-0.5219；分别为P=0.001）和CVD患者亚组（HR，0.2879；95CI，0.0878-0.994；P<.049；和HR，0.1329；95CI，0.024-0.6768；P=0.014）。
结论：启动联合治疗（SGLT2i和GLP1ra）与单独治疗SGLT2i或GLP1ra与较低的癌症死亡风险相关，多见于有或没有CVD的糖尿病患者。虽然还需要临床试验,这些结果可能由这些药物的互补机制来解释，包括它们的抗增殖，抗炎,和代谢作用。未来的临床试验和机制研究将阐明这些药物在致癌作用中的可能作用。
方法：我们对服用SGLT2i的患者进行了一项非并发观察性前瞻性研究，GLP1ra,或者两者兼而有之。在整个人群和CVD患者亚组中进行多项倾向评分。多变量Cox回归分析用于确定年龄的风险比(HR)，性别,危险因素，以及对每个结果的治疗。
结果：我们纳入了14709例患者（11366例SGLT2i，1016与GLP1ra，和2327两种治疗）从治疗开始。97%的患者出现糖尿病。CVD亚组包括4957例(33.7%)患者。在中位随访33个月后，有和无CVD患者的不良癌症事件风险相似(3.4%或3.7%,分别)。癌症死亡的主要危险因素是男性性别和年龄。与SGLT2i或GLP1ra的单药治疗相比，在总体人群中，联合治疗及其持续时间降低了癌症死亡率的风险（HR，0.2216；95CI，0.1106-0.4659；P<.001；和HR，0.1928；95CI，0.071-0.5219；分别为P=0.001）和CVD患者亚组（HR，0.2879；95CI，0.0878-0.994；P<.049；和HR，0.1329；95CI，0.024-0.6768；P=0.014）。
结论：启动联合治疗（SGLT2i和GLP1ra）与单独治疗SGLT2i或GLP1ra与较低的癌症死亡风险相关，多见于有或没有CVD的糖尿病患者。虽然还需要临床试验,这些结果可能由这些药物的互补机制来解释，包括它们的抗增殖，抗炎,和代谢作用。未来的临床试验和机制研究将阐明这些药物在致癌作用中的可能作用。
