■13种人类恶性肿瘤已被确定为肥胖相关癌症(OAC),ie,在患有这些特定肿瘤的患者中,体内脂肪过多与罹患癌症的风险增加和预后恶化相关.胰高血糖素样肽受体激动剂(GLP-1RA)类药物是治疗2型糖尿病(T2D)和实现体重减轻的有效药物,但GLP-1RAs与13例OAC的事件风险之间的关联尚不清楚.
■比较服用GLP-1RA与胰岛素或二甲双胍的T2D患者中13种OAC各自的事件风险。
这项回顾性队列研究是基于一个全国性的多中心电子健康记录数据库(EHR),其中有1.13亿美国患者。研究人群包括1651452例T2D患者,这些患者先前没有OAC的诊断,并服用了GLP-1RA,胰岛素,或二甲双胍在2005年3月至2018年11月期间。数据分析于2024年4月26日进行。
■GLP-1RA处方,胰岛素,或者二甲双胍.
■使用Cox比例风险和Kaplan-Meier生存分析(审查)检查了在暴露后15年随访期间发生的13种OAC中的每一种的事件(首次)诊断。危险比(HR),累积发生率,并计算95%CI。所有模型在基线时通过倾向评分匹配基线协变量校正混杂因素。
■在1651452名T2D患者的研究人群中(平均[SD]年龄,59.8[15.1]年;827873[50.1%]男性和775687[47.0%]女性参与者;5780[0.4%]美洲印第安人或阿拉斯加原住民,65893[4.0%]亚洲人,281242[17.0%]黑色,13707[0.8%]夏威夷原住民或其他太平洋岛民,和1000780[60.6%]白人参与者),与胰岛素相比,GLP-1RA与13种OAC中的10种风险显着降低相关,包括胆囊癌(HR,0.35;95%CI,0.15-0.83),脑膜瘤(HR,0.37;95%CI,0.18-0.74),胰腺癌(HR,0.41;95%CI,0.33-0.50),肝细胞癌(HR,0.47;95%CI,0.36-0.61),卵巢癌(HR,0.52;95%CI,0.03-0.74),结直肠癌(HR,0.54;95%CI,0.46-0.64),多发性骨髓瘤(HR,0.59;95%CI,0.44-0.77),食管癌(HR,0.60;95%CI,0.42-0.86),子宫内膜癌(HR,0.74;95%CI,0.60-0.91),和肾癌(HR,0.76;95%CI,0.64-0.91)。虽然没有统计学意义,与服用胰岛素的患者相比,服用GLP-1RA的胃癌患者的HR小于1(HR,0.73;95%CI,0.51-1.03)。GLP-1RA与绝经后乳腺癌或甲状腺癌的风险降低无关。与服用胰岛素的患者相比,在服用GLP-1RA的患者中显示出风险降低的癌症中,服用GLP-1RAs与服用二甲双胍治疗结直肠癌和胆囊癌的患者的HR小于1,但风险降低无统计学意义。与二甲双胍相比,GLP-1RA与任何癌症风险的降低无关,但与肾癌风险增加相关(HR,1.54;95%CI,1.27-1.87)。
■在这项研究中,T2D患者与胰岛素或二甲双胍相比,GLP-1RA与特定类型OAC的风险较低相关。这些发现为GLP-1RA在高危人群中预防癌症的潜在益处提供了初步证据,并支持进一步的临床前和临床研究来预防某些OAC。
UNASSIGNED: Thirteen human malignant neoplasms have been identified as obesity-associated cancers (OACs), ie, the presence of excess body fat is associated with increased risk of developing cancer and worse prognosis in patients with these specific tumors. The glucagon-like peptide receptor agonist (GLP-1RA) class of pharmaceuticals are effective agents for the treatment of type 2 diabetes (T2D) and for achieving weight loss, but the association of GLP-1RAs with the incident risk of 13 OACs is unclear.
UNASSIGNED: To compare the incident risk of each of the 13 OACs in patients with T2D who were prescribed GLP-1RAs vs insulins or
metformin.
UNASSIGNED: This retrospective cohort study was based on a nationwide multicenter database of electronic health records (EHRs) of 113 million US patients. The study population included 1 651 452 patients with T2D who had no prior diagnosis of OACs and were prescribed GLP-1RAs, insulins, or
metformin during March 2005 to November 2018. Data analysis was conducted on April 26, 2024.
UNASSIGNED: Prescription of GLP-1RAs, insulins, or
metformin.
UNASSIGNED: Incident (first-time) diagnosis of each of the 13 OACs occurring during a 15-year follow-up after the exposure was examined using Cox proportional hazard and Kaplan-Meier survival analyses with censoring applied. Hazard ratios (HRs), cumulative incidences, and 95% CIs were calculated. All models were adjusted for confounders at baseline by propensity-score matching baseline covariates.
UNASSIGNED: In the study population of 1 651 452 patients with T2D (mean [SD] age, 59.8 [15.1] years; 827 873 [50.1%] male and 775 687 [47.0%] female participants; 5780 [0.4%] American Indian or Alaska Native, 65 893 [4.0%] Asian, 281 242 [17.0%] Black, 13 707 [0.8%] Native Hawaiian or Other Pacific Islander, and 1 000 780 [60.6%] White participants), GLP-1RAs compared with insulin were associated with a significant risk reduction in 10 of 13 OACs, including in gallbladder cancer (HR, 0.35; 95% CI, 0.15-0.83), meningioma (HR, 0.37; 95% CI, 0.18-0.74), pancreatic cancer (HR, 0.41; 95% CI, 0.33-0.50), hepatocellular carcinoma (HR, 0.47; 95% CI, 0.36-0.61), ovarian cancer (HR, 0.52; 95% CI, 0.03-0.74), colorectal cancer (HR, 0.54; 95% CI, 0.46-0.64), multiple myeloma (HR, 0.59; 95% CI, 0.44-0.77), esophageal cancer (HR, 0.60; 95% CI, 0.42-0.86), endometrial cancer (HR, 0.74; 95% CI, 0.60-0.91), and kidney cancer (HR, 0.76; 95% CI, 0.64-0.91). Although not statistically significant, the HR for stomach cancer was less than 1 among patients who took GLP-1RAs compared with those who took insulin (HR, 0.73; 95% CI, 0.51-1.03). GLP-1RAs were not associated with a reduced risk of postmenopausal breast cancer or thyroid cancer. Of those cancers that showed a decreased risk among patients taking GLP-1RAs compared with those taking insulin, HRs for patients taking GLP-1RAs vs those taking
metformin for colorectal and gallbladder cancer were less than 1, but the risk reduction was not statistically significant. Compared with
metformin, GLP-1RAs were not associated with a decreased risk of any cancers, but were associated with an increased risk of kidney cancer (HR, 1.54; 95% CI, 1.27-1.87).
UNASSIGNED: In this study, GLP-1RAs were associated with lower risks of specific types of OACs compared with insulins or metformin in patients with T2D. These findings provide preliminary evidence of the potential benefit of GLP-1RAs for cancer prevention in high-risk populations and support further preclinical and clinical studies for the prevention of certain OACs.