Abstract：
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been suggested to possess antineoplastic properties against prostate cancer. We examined the association between GLP-1RA use and prostate cancer risk in a real-world setting.
We performed a nationwide register-based cohort study using an active-comparator, new-user design. We included all men in Denmark aged ≥50 years who commenced use of GLP-1RAs or basal insulin during 2007-2019. HRs and 95% CIs for incident prostate cancer were estimated using multivariable Cox regression in \'intention-to-treat\' (ITT)- and \'per-protocol\'-like analyses.
Among 14,206 initiators of GLP-1RAs and 21,756 initiators of basal insulin, we identified 697 patients with prostate cancer during a mean follow-up period of about 5 years from initiation of the study drugs. In comparison with basal insulin use, GLP-1RA use was associated with an adjusted HR of 0.91 (95% CI 0.73, 1.14) in the \'ITT\' analysis and 0.80 (95% CI 0.64, 1.01) in the \'per-protocol\' analysis. Stronger inverse associations were seen among older men (≥70 years) (\'ITT\' HR 0.56; 95% CI 0.38, 0.82; \'per-protocol\' HR 0.47; 95% CI 0.30, 0.74), and in patients with CVD (\'ITT\' HR 0.75; 95% CI 0.53, 1.06; \'per-protocol\' HR 0.60; 95% CI 0.39, 0.91).
GLP-1RA use was inversely associated with prostate cancer risk compared with use of basal insulin in the \'per-protocol\' analysis. Older men and patients with CVD exhibited stronger inverse associations in both the \'ITT\' and \'per-protocol\' analyses. Our results may indicate that GLP-1RA use could protect against prostate cancer.
We performed a nationwide register-based cohort study using an active-comparator, new-user design. We included all men in Denmark aged ≥50 years who commenced use of GLP-1RAs or basal insulin during 2007-2019. HRs and 95% CIs for incident prostate cancer were estimated using multivariable Cox regression in \'intention-to-treat\' (ITT)- and \'per-protocol\'-like analyses.
Among 14,206 initiators of GLP-1RAs and 21,756 initiators of basal insulin, we identified 697 patients with prostate cancer during a mean follow-up period of about 5 years from initiation of the study drugs. In comparison with basal insulin use, GLP-1RA use was associated with an adjusted HR of 0.91 (95% CI 0.73, 1.14) in the \'ITT\' analysis and 0.80 (95% CI 0.64, 1.01) in the \'per-protocol\' analysis. Stronger inverse associations were seen among older men (≥70 years) (\'ITT\' HR 0.56; 95% CI 0.38, 0.82; \'per-protocol\' HR 0.47; 95% CI 0.30, 0.74), and in patients with CVD (\'ITT\' HR 0.75; 95% CI 0.53, 1.06; \'per-protocol\' HR 0.60; 95% CI 0.39, 0.91).
GLP-1RA use was inversely associated with prostate cancer risk compared with use of basal insulin in the \'per-protocol\' analysis. Older men and patients with CVD exhibited stronger inverse associations in both the \'ITT\' and \'per-protocol\' analyses. Our results may indicate that GLP-1RA use could protect against prostate cancer.
摘要：
目的：胰高血糖素样肽-1受体激动剂（GLP-1RAs）被认为具有抗前列腺癌的抗肿瘤特性。我们研究了在现实世界中使用GLP-1RA与前列腺癌风险之间的关联。
方法：我们使用主动比较器进行了一项全国性的基于注册的队列研究，新用户设计。我们纳入了2007-2019年期间开始使用GLP-1RAs或基础胰岛素的所有年龄≥50岁的丹麦男性。在“意向治疗”（ITT）和“符合方案”样分析中，使用多变量Cox回归估算了偶发前列腺癌的HR和95％CI。
结果：在14,206名GLP-1RA的引发剂和21,756名基础胰岛素的引发剂中，我们在研究药物开始后约5年的平均随访期间确定了697例前列腺癌患者.与基础胰岛素使用相比，在ITT分析中，GLP-1RA的使用与0.91(95%CI0.73,1.14)的校正HR相关，在符合方案分析中，GLP-1RA的使用与0.80(95%CI0.64,1.01)相关。在年龄较大的男性（≥70岁）中发现了更强的逆关联（\'ITT\'HR0.56;95％CI0.38，0.82;\'按方案的HR0.47;95％CI0.30，0.74），和CVD患者(ITTHR0.75;95%CI0.53,1.06;符合方案HR0.60;95%CI0.39,0.91)。
结论：在“符合方案”分析中，与使用基础胰岛素相比，使用GLP-1RA与前列腺癌风险呈负相关。在“ITT”和“符合方案”分析中，老年男性和CVD患者均表现出较强的负相关。我们的结果可能表明使用GLP-1RA可以预防前列腺癌。
方法：我们使用主动比较器进行了一项全国性的基于注册的队列研究，新用户设计。我们纳入了2007-2019年期间开始使用GLP-1RAs或基础胰岛素的所有年龄≥50岁的丹麦男性。在“意向治疗”（ITT）和“符合方案”样分析中，使用多变量Cox回归估算了偶发前列腺癌的HR和95％CI。
结果：在14,206名GLP-1RA的引发剂和21,756名基础胰岛素的引发剂中，我们在研究药物开始后约5年的平均随访期间确定了697例前列腺癌患者.与基础胰岛素使用相比，在ITT分析中，GLP-1RA的使用与0.91(95%CI0.73,1.14)的校正HR相关，在符合方案分析中，GLP-1RA的使用与0.80(95%CI0.64,1.01)相关。在年龄较大的男性（≥70岁）中发现了更强的逆关联（\'ITT\'HR0.56;95％CI0.38，0.82;\'按方案的HR0.47;95％CI0.30，0.74），和CVD患者(ITTHR0.75;95%CI0.53,1.06;符合方案HR0.60;95%CI0.39,0.91)。
结论：在“符合方案”分析中，与使用基础胰岛素相比，使用GLP-1RA与前列腺癌风险呈负相关。在“ITT”和“符合方案”分析中，老年男性和CVD患者均表现出较强的负相关。我们的结果可能表明使用GLP-1RA可以预防前列腺癌。
