【真相】可靠数据力证肠促胰岛素类药物与胰腺炎风险无关！

Diabetes Obes Metab杂志提前在线发表的一项荟萃分析探讨了肠促胰岛素类降血糖药物与急性胰腺炎发生风险之间的关系。该分析共纳入9项研究，涉及超过130万例患者，其中有5195例患者发生过急性胰腺炎。研究者发现，肠促胰岛素类药物治疗患者发生急性胰腺炎的比值比为1.03，提示在糖尿病患者中使用肠促胰岛素类药物与急性胰腺炎发生风险之间无明显相关性。瑞典隆德大学临床代谢病研究所Bo Ahrén教授对此进行了点评。

专家点评

瑞典隆德大学临床代谢病研究所Bo Ahrén教授

2型糖尿病患者急性胰腺炎发生风险增加2~3倍。近年来，关于肠促胰岛素类药物（GLP-1受体激动剂和DPP-4抑制剂）是否会进一步增加糖尿病患者急性胰腺炎风险已进行了大量的讨论。然而在2013年，一项单中心小样本研究发现肠促胰岛素类药物可引起胰腺形态学改变，使得这个讨论再次引起广泛关注。但是，由于这项研究没有有力的科学支撑，研究结果受到广泛质疑。此外，2013-2014年最新发布的大量临床数据也都显示，肠促胰岛素类药物治疗与急性胰腺炎发生之间没有明显相关性。因此，当前的数据提示，肠促胰岛素类药物治疗与急性胰腺炎之间的任何相关性都是如此微弱，以至于在临床实践中很难检测到。

在DPP-4抑制剂和GLP-1受体激动剂荟萃分析研究、2项大型肠促胰岛素类药物心血管预后研究、以及23项DPP-4抑制剂研究和38项GLP-1受体激动剂研究汇总分析（涉及超过30000例患者）中，都已证实肠促胰岛素类药物治疗与急性胰腺炎之间无明显相关性。

最近，真实世界观察性研究的研究报告中公开了一些更加可靠的数据，这项研究共纳入超过130万例，其中有20多万例患者使用肠促胰岛素类药物治疗。并且，在这些研究中，共有超过5000例患者发生过急性胰腺炎，这些数据可以确保这项研究能比以往研究有更加精确的评估结果。研究发现，肠促胰岛素类药物治疗患者发生急性胰腺炎的估算比值比为1.03（95%CI，0.87-1.20），也就是说，两者之间无明显相关性。

依据以上数据，我们现在可以得出一个比较肯定的结论，当给予患者肠促胰岛素类药物治疗时，并不会导致患者急性胰腺炎发生风险显著增加。当与患者进行沟通时，以及起始和评估治疗方案时，这些可靠的数据对我们尤为重要。但是，肠促胰岛素类药物与急性胰腺炎之间也可能存在极其罕见的相关性，因此，在观察性研究和即将公开的心血管预后研究中继续评估肠促胰岛素类药物的这种不良事件是非要重要的。此外，在既往有急性胰腺炎病史患者中避免使用肠促胰岛素类药物治疗同时也是明智之举，但前提是患者之前得到正确诊断。

TAKE-HOME MESSAGE

This study sought a connection between incretin-based therapy for diabetes with the development of acute pancreatitis.

Through a meta-analysis of nine studies, including more than 1.3 million patients and 5195 occurrences of acute pancreatitis, an odds ratio of 1.03 was calculated (95% CI), indicating no association in this population.

Expert Comment

Bo Ahrén MD

Professor in Clinical Metabolic Research at Lund University

The occurrence of acute pancreatitis is increased two- to threefold in individuals with type 2 diabetes.1 During recent years, it has been heavily discussed whether incretin-based therapy (GLP-1 receptor agonists and DPP-4 inhibitors) further increases this risk. In 2013 this discussion was accentuated by a single small study on morphology of pancreata.2 However, this study was heavily criticized for scientific weakness.3-5 Furthermore, a large body of clinical data emerging in 2013 and 2014 has shown that there is no statistical association between incretin therapy and occurrence of acute pancreatitis. Therefore, the data today suggest that any association between incretin-based therapy and acute pancreatitis is so weak that it is impossible to detect in practice.

This absence of association between incretin-based therapy and acute pancreatitis has been demonstrated in meta-analyses of studies on DPP-4 inhibitors and GLP-1 receptor agonists,6,7 in 2 large cardiovascular outcomes studies with incretin therapy,8,9 and in a pooled analysis of 23 studies with DPP-4 inhibitors and 38 studies with GLP-1 receptor agonists with more than 30,000 patients.10

Very recently, further reassuring data were disclosed in a study reporting data from observational “real-world” studies comprising more than 1.3 million patients (>200,000 were treated with incretin therapy).11 In these studies, >5000 cases of acute pancreatitis developed, which assured a more accurate estimation than in previous studies. The estimate odds ratio for association between these cases and incretin therapy was 1.03 (95% CI, 0.87–1.20); that is, no significant association.

With all these data, we can now firmly conclude that there is no obvious increased risk for acute pancreatitis when treating patients with incretin therapy. These reassuring data are important for us when discussing with patients and when initiating and evaluating therapy. Still, an extremely rare association could exist, and therefore it is important to continue to evaluate this adverse event in observational studies and in the upcoming disclosures of cardiovascular outcomes studies. It is also wise to avoid initiating incretin therapy in patients with previous history of acute pancreatitis, provided that it has been properly diagnosed. 

Diabetes, Obesity & Metabolism

Using Real-World Data to Evaluate the Association of Incretin-Based Therapies With Risk of Acute Pancreatitis: A Meta-Analysis of 1 324 515 Patients From Observational Studies

Diabetes Obes Metab 2015 Jan 01;17(1)32-41, T Wang, F Wang, Z Gou, H Tang, C Li, L Shi, S Zhai

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

This abstract is available on the publisher's site.

Access this abstract now

Copyright © 2014 Elsevier Inc. All rights reserved.

独家授权，未经许可，请勿转载