Diabetes Center Bochum-Hattingen, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany
Novo Nordisk A/S, Søborg, Denmark.
Diabetes Care. 2019 Oct;42(10):1912-1920. doi: 10.2337/dc19-0415. Epub 2019 Aug 9.
To explore gallbladder- and biliary tract-related events reported for the liraglutide and placebo groups in the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial.
LEADER was an international, randomized, double-blind, controlled cardiovascular (CV) outcomes trial. Participants with type 2 diabetes at high risk for CV events ( = 9,340) were randomized 1:1 to receive either liraglutide (≤1.8 mg daily; = 4,668) or placebo ( = 4,672), with both groups also receiving standard care (treatment period: 3.5-5 years). Acute gallstone disease was a medical event of special interest. This post hoc analysis categorized captured events of acute gallbladder or biliary disease into four groups: uncomplicated gallbladder stones, complicated gallbladder stones, cholecystitis, and biliary obstruction. Time to first event by treatment group was analyzed using Cox regression.
There was an increased risk of acute gallbladder or biliary disease with liraglutide versus placebo ( = 141 of 4,668 vs. = 88 of 4,672 patients, respectively; hazard ratio [HR] 1.60; 95% CI 1.23, 2.09; < 0.001). Similar trends were observed for each of the four categories of gallbladder- or biliary tract-related events. Cholecystectomy was performed more frequently in liraglutide-treated patients (HR 1.56; 95% CI 1.10, 2.20; = 0.013) but for similar proportions of the patients who experienced gallbladder- or biliary tract-related events (57% with liraglutide vs. 59% with placebo).
Although LEADER was not specifically designed to assess acute gallbladder or biliary disease, the trial showed an increased risk of gallbladder- or biliary tract-related events with liraglutide versus placebo, which appeared to be consistent across four categories of these events. Further studies should investigate the relevant mechanisms.
探讨利拉鲁肽组和安慰剂组在利拉鲁肽与糖尿病：心血管结局评价（LEADER）试验中报告的胆囊和胆道相关事件。
LEADER 是一项国际性、随机、双盲、对照心血管（CV）结局试验。9340 名有发生 CV 事件高危因素的 2 型糖尿病患者按 1:1 随机分为利拉鲁肽（≤1.8 mg/日；n=4668）或安慰剂（n=4672）组，两组均接受标准治疗（治疗期：3.5-5 年）。急性胆石病是一个特别关注的医学事件。本事后分析将捕捉到的急性胆囊或胆道疾病事件分为 4 组：单纯胆囊结石、复杂胆囊结石、胆囊炎和胆道梗阻。采用 Cox 回归分析治疗组的首次事件时间。
与安慰剂相比，利拉鲁肽治疗组发生急性胆囊或胆道疾病的风险增加（利拉鲁肽组 4668 例患者中有 141 例，安慰剂组 4672 例患者中有 88 例；风险比[HR]1.60；95%CI 1.23，2.09；<0.001）。四种类型的胆囊或胆道相关事件均有类似的趋势。利拉鲁肽治疗组行胆囊切除术的频率更高（HR 1.56；95%CI 1.10，2.20；=0.013），但在经历胆囊或胆道相关事件的患者中所占比例相似（利拉鲁肽组 57%，安慰剂组 59%）。
尽管 LEADER 并非专门用于评估急性胆囊或胆道疾病，但该试验显示，与安慰剂相比，利拉鲁肽治疗组发生胆囊或胆道相关事件的风险增加，这在这四类事件中似乎一致。需要进一步的研究来调查相关机制。
