Skriver Charlotte, Friis Søren, Knudsen Lotte B, Catarig Andrei-Mircea, Clark Alice J, Dehlendorff Christian, Mørch Lina S
Cancer Surveillance and Pharmacoepidemiology, Danish Cancer Society Research Center, Copenhagen, Denmark.
Novo Nordisk A/S, Bagsvaerd, Denmark.
Diabetologia. 2023 Nov;66(11):2007-2016. doi: 10.1007/s00125-023-05972-x. Epub 2023 Aug 3.
AIMS/HYPOTHESIS: 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).
CONCLUSIONS/INTERPRETATION: 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.
目的/假设：胰高血糖素样肽-1受体激动剂（GLP-1RAs）已被认为具有抗前列腺癌的特性。我们在真实世界环境中研究了GLP-1RAs的使用与前列腺癌风险之间的关联。
我们采用活性对照、新使用者设计进行了一项基于全国登记的队列研究。我们纳入了丹麦所有年龄≥50岁且在2007 - 2019年期间开始使用GLP-1RAs或基础胰岛素的男性。在“意向性治疗”（ITT）和“符合方案”类分析中，使用多变量Cox回归估计前列腺癌发病的风险比（HRs）和95%置信区间（CIs）。
在14206名GLP-1RAs起始使用者和21756名基础胰岛素起始使用者中，从开始使用研究药物起平均约5年的随访期内，我们确定了697例前列腺癌患者。与使用基础胰岛素相比，在“ITT”分析中，GLP-1RAs使用的校正HR为0.91（95% CI 0.73, 1.14），在“符合方案”分析中为0.80（95% CI 0.64, 1.01）。在老年男性（≥70岁）中观察到更强的负相关（“ITT” HR 0.56；95% CI 0.38, 0.82；“符合方案” HR 0.47；95% CI 0.30, 0.74），在患有心血管疾病（CVD）的患者中也是如此（“ITT” HR 0.75；95% CI 0.53, 1.06；“符合方案” HR 0.60；95% CI 0.39, 0.91）。
结论/解读：在“符合方案”分析中，与使用基础胰岛素相比，GLP-1RAs的使用与前列腺癌风险呈负相关。在“ITT”和“符合方案”分析中，老年男性和患有CVD的患者均表现出更强的负相关。我们的结果可能表明使用GLP-1RAs可预防前列腺癌。
