Endocrine and Metabolism Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
Graduate Program in Medical Sciences (Endocrinology), Department of Internal Medicine, Faculty of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
J Clin Endocrinol Metab. 2021 Mar 8;106(3):912-921. doi: 10.1210/clinem/dgaa891.
Risk of cancer is a major concern in the development of drugs for the treatment of obesity and diabetes. In randomized controlled trials (RCTs) of the Liraglutide Clinical Development Program, subjects treated with a glucagon-like peptide-1 receptor agonist (GLP-1RA) had a higher absolute number of breast cancer events.
To assess whether patients treated with GLP-1RAs had a higher risk of breast neoplasms.
We searched MEDLINE, Embase, Web of Science, and CENTRAL from July 31, 2019 to February 8, 2020.
Reviewers assessed abstracts and full-text articles for RCTs of GLP-1RAs in adults with excessive weight and/or diabetes and a minimum follow-up of 24 weeks.
Researchers extracted study-level data and assessed within-study risk of bias with the RoB 2.0 tool and quality of evidence with Grading of Recommendations Assessment, Development and Evaluation (GRADE).
We included 52 trials, of which 50 reported breast cancer events and 11 reported benign breast neoplasms. Overall methodological quality was high. Among 48 267 subjects treated with GLP-1RAs, 130 developed breast cancer compared with 107 of 40 755 controls (relative risk [RR], 0.98; 95% confidence interval [CI], 0.76-1.26). Subset analyses according to follow-up, participant/investigator blinding, and type of GLP-1RA did not reveal any differences. The risk of benign breast neoplasms also did not differ between groups (RR, 0.99; 95% CI, 0.48-2.01). Trial sequential analysis provided evidence that the sample size was sufficient to avoid missing alternative results.
Treatment with GLP-1RAs for obesity and diabetes does not increase the risk of breast neoplasms.
癌症风险是肥胖症和糖尿病治疗药物开发的主要关注点。在利拉鲁肽临床开发项目的随机对照试验 (RCT) 中，接受胰高血糖素样肽-1 受体激动剂 (GLP-1RA) 治疗的受试者发生乳腺癌事件的绝对数量更高。
评估接受 GLP-1RA 治疗的患者是否有更高的乳腺肿瘤风险。
我们于 2019 年 7 月 31 日至 2020 年 2 月 8 日在 MEDLINE、Embase、Web of Science 和 CENTRAL 进行了检索。
审查员评估了 RCT 的摘要和全文，这些 RCT 针对超重和/或糖尿病的成年人，且随访时间至少为 24 周。
研究人员提取了研究水平的数据，并使用 RoB 2.0 工具评估了研究内的偏倚风险，使用 Grading of Recommendations Assessment, Development and Evaluation (GRADE) 评估了证据质量。
我们纳入了 52 项试验，其中 50 项报告了乳腺癌事件，11 项报告了良性乳腺肿瘤。整体方法学质量较高。在接受 GLP-1RA 治疗的 48267 名受试者中，有 130 人发生乳腺癌，而在 40755 名对照组中，有 107 人发生乳腺癌（相对风险 [RR]，0.98；95%置信区间 [CI]，0.76-1.26）。根据随访、参与者/研究者盲法和 GLP-1RA 类型进行的亚组分析并未发现差异。两组之间良性乳腺肿瘤的风险也没有差异（RR，0.99；95%CI，0.48-2.01）。试验序贯分析提供了证据表明，样本量足以避免错过替代结果。
肥胖症和糖尿病患者使用 GLP-1RA 治疗不会增加乳腺肿瘤的风险。
