2025年2月26日出版的《英国医学杂志》发表了加拿大科学家的一项最新研究成果。来自犹太总医院的Laurent Azoulay研究小组报道了lucagon-like peptide-1受体激动剂与2型糖尿病患者自杀风险。

目的:与使用二肽基肽酶-4 （DPP-4）抑制剂或钠-葡萄糖共转运蛋白-2 （SGLT-2）抑制剂相比，确定使用胰高血糖素样肽-1 （GLP-1）受体激动剂是否与2型糖尿病患者自杀意念、自残和自杀风险增加有关。

设计:主动比较者，新用户队列研究。

设置:初级保健实践为英国临床实践研究数据链提供数据，该数据链与医院事件统计入院患者护理和国家统计办公室死亡登记数据库相连。

参与者:2型糖尿病患者。本研究收集了两个队列，第一个队列由2007年1月1日至2020年12月31日期间开始并继续使用GLP-1受体激动剂或DPP-4抑制剂的患者组成，第二个队列由2013年1月1日至2020年12月31日期间开始并继续使用GLP-1受体激动剂或SGLT-2抑制剂的患者组成。两个队列的随访一直持续到2021年3月29日。

主要结果测量：主要结果是自杀倾向，定义为自杀意念、自残和自杀的综合表现。次要结局分别考虑这些事件。采用倾向评分精细分层加权Cox比例风险模型估计风险比，95%置信区间（CI）估计治疗患者的平均治疗效果。

结果:第一组包括36082名GLP-1受体激动剂使用者（中位随访1.3年）和234028名DPP-4抑制剂使用者（中位随访时间为1.7年）。在初步分析中，与DPP-4抑制剂相比，GLP-1受体激动剂的使用与自杀发生率增加有关(粗发生率分别为3.9和1.8 / 1000人年；风险比2.08,95% CI 1.83 ~ 2.36)。在考虑了混杂因素后，该估计降低为零值（风险比1.02,95% CI 0.85至1.23）。第二组包括32336名GLP-1受体激动剂使用者（中位随访时间1.2年）和96212名SGLT-2抑制剂使用者（中位随访期1.2年）。同样，在粗分析中，与SGLT-2抑制剂相比，GLP-1受体激动剂的使用与自杀风险增加相关(粗发病率为4.3 v 2.7 / 1000人年；风险比1.60,95% CI 1.37 ~ 1.87)，但考虑了混杂因素后（0.91,0.73 ~ 1.12）。当对两组人群分别分析自杀意念、自残和自杀时，也观察到类似的结果。

研究结果表明，在这项大型队列研究中，与使用DPP-4抑制剂或SGLT-2抑制剂相比，2型糖尿病患者使用GLP-1受体激动剂与自杀风险增加无关。

附：英文原文

Title: Glucagon-like peptide-1 receptor agonists and risk of suicidality among patients with type 2 diabetes: active comparator, new user cohort study

Author: Samantha B Shapiro, Hui Yin, Oriana Hoi Yun Yu, Soham Rej, Samy Suissa, Laurent Azoulay

Issue&Volume: 2025/02/26

Abstract: Objective To determine whether the use of glucagon-like peptide-1 (GLP-1) receptor agonists is associated with an increased risk of suicidal ideation, self-harm, and suicide among patients with type 2 diabetes compared with the use of dipeptidyl peptidase-4 (DPP-4) inhibitors or sodium-glucose cotransporter-2 (SGLT-2) inhibitors.

Design Active comparator, new user cohort study.

Setting Primary care practices contributing data to the UK Clinical Practice Research Datalink linked to the Hospital Episodes Statistics Admitted Patient Care and Office for National Statistics Death Registration databases.

Participants Patients with type 2 diabetes.

Exposures Two cohorts were assembled, with the first composed of patients who started and continued on GLP-1 receptor agonists or DPP-4 inhibitors between 1 January 2007 and 31 December 2020 and the second composed of patients who started and continued on GLP-1 receptor agonists or SGLT-2 inhibitors between 1 January 1 2013 and 31 December 2020. Both cohorts were followed until 29 March 2021.

Main outcome measures The primary outcome was suicidality, defined as a composite of suicidal ideation, self-harm, and suicide. Secondary outcomes were each of these events considered separately. Propensity score fine stratification weighted Cox proportional hazards models were fitted to estimate hazard ratios and 95% confidence intervals (CIs) to estimate the average treatment effect among the treated patients.

Results The first cohort included 36082 GLP-1 receptor agonist users (median follow-up 1.3 years) and 234028 DPP-4 inhibitor users (median follow-up 1.7 years). In crude analyses, GLP-1 receptor agonist use was associated with an increased incidence of suicidality compared with DPP-4 inhibitors (crude incidence rates 3.9 v 1.8 per 1000 person years, respectively; hazard ratio 2.08, 95% CI 1.83 to 2.36). This estimate decreased to a null value after confounding factors were accounted for (hazard ratio 1.02, 95% CI 0.85 to 1.23). The second cohort included 32336 GLP-1 receptor agonist users (median follow-up 1.2 years) and 96212 SGLT-2 inhibitor users (median follow-up 1.2 years). Similarly, GLP-1 receptor agonist use was associated with an increased risk of suicidality compared with SGLT-2 inhibitors in crude analyses (crude incidence rates 4.3 v 2.7 per 1000 person years; hazard ratio 1.60, 95% CI 1.37 to 1.87) but not after confounding factors were accounted for (0.91, 0.73 to 1.12). Similar findings were observed when suicidal ideation, self-harm, and suicide were analysed separately in both cohorts.

Conclusions In this large cohort study, the use of GLP-1 receptor agonists was not associated with an increased risk of suicidality compared with the use of DPP-4 inhibitors or SGLT-2 inhibitors in patients with type 2 diabetes.

DOI: 10.1136/bmj-2024-080679

Source: https://www.bmj.com/content/388/bmj-2024-080679