Diabetes Center Bochum-Hattingen, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany
Novo Nordisk A/S, Bagsværd, Denmark.
Diabetes Care. 2018 Aug;41(8):1663-1671. doi: 10.2337/dc17-1825. Epub 2018 Jun 13.
This study explored neoplasm risk with liraglutide versus placebo in the LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) cohort.
LEADER (NCT01179048) was an international, phase 3b, randomized, double-blind, controlled trial. Participants aged ≥50 years with type 2 diabetes and high cardiovascular risk were assigned 1:1 to receive liraglutide (≤1.8 mg daily; = 4,668) or placebo ( = 4,672) in addition to standard care and monitored for 3.5-5 years (median follow-up 3.8 years). The occurrence of neoplasms was a prespecified, exploratory secondary end point. Post hoc analyses of the time to the first confirmed neoplasms were conducted using a Cox regression model.
Neoplasm was confirmed in 10.1% of patients with liraglutide versus 9.0% with placebo (hazard ratio [HR] 1.12 [95% CI 0.99; 1.28]). The HR (95% CI) for liraglutide versus placebo was 1.06 (0.90; 1.25) for malignant neoplasms and 1.16 (0.93; 1.44) for benign neoplasms. Sensitivity analyses excluding neoplasms occurring <1 year or <2 years after randomization and analyses by sex provided similar results. In our main analyses, the 95% CI for the HR included one for all malignant neoplasms evaluated (including pancreatic and thyroid neoplasms) except for prostate neoplasms, which occurred in fewer liraglutide-treated patients.
LEADER was not primarily designed to assess neoplasm risk. Firm conclusions cannot be made regarding numeric imbalances observed for individual neoplasm types (e.g., pancreatic cancer) that occurred infrequently. LEADER data do, however, exclude a major increase in the risk of total malignant neoplasms with liraglutide versus placebo. Additional studies are needed to assess longer-term exposure.
本研究旨在探讨利拉鲁肽与安慰剂在 LEADER（利拉鲁肽对糖尿病的作用和疗效：心血管结局评估）队列中的肿瘤风险。
LEADER（NCT01179048）是一项国际性的、3b 期、随机、双盲、对照临床试验。年龄≥50 岁、患有 2 型糖尿病且伴有高心血管风险的患者按 1:1 比例被分配至接受利拉鲁肽（每日≤1.8mg；n=4668）或安慰剂（n=4672）治疗，同时接受标准治疗，并随访 3.5-5 年（中位随访时间 3.8 年）。肿瘤的发生是预先设定的探索性次要终点。采用 Cox 回归模型对首次确诊肿瘤的时间进行了事后分析。
利拉鲁肽组患者中有 10.1%确诊患有肿瘤，安慰剂组患者中有 9.0%确诊患有肿瘤（风险比 [HR]1.12 [95%CI 0.99；1.28]）。利拉鲁肽组与安慰剂组的 HR（95%CI）分别为恶性肿瘤 1.06（0.90；1.25）和良性肿瘤 1.16（0.93；1.44）。排除随机分组后 1 年内或 2 年内发生的肿瘤，以及按性别进行分析，结果相似。在我们的主要分析中，HR 的 95%CI 包括除前列腺肿瘤以外的所有评估的恶性肿瘤（包括胰腺和甲状腺肿瘤），但利拉鲁肽组中发生的前列腺肿瘤较少。
LEADER 主要不是为了评估肿瘤风险而设计的。对于个别肿瘤类型（如胰腺癌）观察到的数值不平衡，不能得出明确的结论，因为这些肿瘤的发生频率较低。然而，LEADER 数据排除了利拉鲁肽与安慰剂相比恶性肿瘤总风险的显著增加。需要进一步的研究来评估更长时间的暴露情况。
