Division of Clinical Epidemiology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
JAMA Intern Med. 2024 Nov 1;184(11):1301-1312. doi: 10.1001/jamainternmed.2024.4369.
Concerns have been raised regarding a link between use of glucagon-like peptide-1 (GLP-1) receptor agonists and increased risk of suicidality and self-harm.
To assess the association between use of GLP-1 receptor agonists and the risk of suicide death in routine clinical practice.
DESIGN, SETTING, AND PARTICIPANTS: This active-comparator new-user cohort study used nationwide register data from Sweden and Denmark from 2013 to 2021. Adults 18 to 84 years old who initiated treatment with GLP-1 receptor agonists or the comparator sodium-glucose cotransporter-2 (SGLT2) inhibitors were included. Data were analyzed from March to June 2024.
Initiation of treatment with a GLP-1 receptor agonist or SGLT2 inhibitor.
The primary outcome was suicide death recorded in the cause of death registers. Secondary outcomes were the composite of suicide death and nonfatal self-harm and the composite of incident depression and anxiety-related disorders. Using propensity score weighting, hazard ratios (HRs) with 95% CIs were calculated separately in the 2 countries and pooled in a meta-analysis.
In total, 124 517 adults initiated a GLP-1 receptor agonist and 174 036 initiated an SGLT2 inhibitor; among GLP-1 receptor agonist users, the mean (SD) age was 60 (13) years, and 45% were women. During a mean (SD) follow-up of 2.5 (1.7) years, 77 suicide deaths occurred among users of GLP-1 receptor agonists and 71 suicide deaths occurred among users of SGLT2 inhibitors: weighted incidences were 0.23 vs 0.18 events per 1000 person-years (HR, 1.25; 95% CI, 0.83-1.88), with an absolute difference of 0.05 (95% CI, -0.03 to 0.16) events per 1000 person-years. The HR was 0.83 (95% CI, 0.70-0.97) for suicide death and nonfatal self-harm, and the HR was 1.01 (95% CI, 0.97-1.06) for incident depression and anxiety-related disorders.
This cohort study, including mostly patients with type 2 diabetes, does not show an association between use of GLP-1 receptor agonists and an increased risk of suicide death, self-harm, or incident depression and anxiety-related disorders. Suicide death among GLP-1 receptor agonist users was rare, and the upper limit of the confidence interval was compatible with an absolute risk increase of no more than 0.16 events per 1000 person-years.
人们对胰高血糖素样肽-1（GLP-1）受体激动剂的使用与自杀和自残风险增加之间的联系表示担忧。
评估 GLP-1 受体激动剂在常规临床实践中的使用与自杀死亡风险之间的关联。
设计、地点和参与者：本主动对照新用户队列研究使用了来自瑞典和丹麦的全国登记数据，时间范围为 2013 年至 2021 年。纳入年龄在 18 至 84 岁之间、开始接受 GLP-1 受体激动剂或比较药物钠-葡萄糖协同转运蛋白 2（SGLT2）抑制剂治疗的成年人。数据分析于 2024 年 3 月至 6 月进行。
开始使用 GLP-1 受体激动剂或 SGLT2 抑制剂。
主要结局是在死因登记处记录的自杀死亡。次要结局是自杀死亡和非致命性自残的复合结局以及新发抑郁和焦虑相关障碍的复合结局。使用倾向评分加权，分别在两个国家计算风险比（HR）和 95%置信区间，并进行荟萃分析。
共有 124517 名成年人开始使用 GLP-1 受体激动剂，174036 名成年人开始使用 SGLT2 抑制剂；GLP-1 受体激动剂使用者的平均（标准差）年龄为 60（13）岁，45%为女性。在平均（标准差）2.5（1.7）年的随访期间，GLP-1 受体激动剂使用者中有 77 人发生自杀死亡，SGLT2 抑制剂使用者中有 71 人发生自杀死亡：加权发生率分别为 0.23 例/1000 人年和 0.18 例/1000 人年（HR，1.25；95%CI，0.83-1.88），绝对差异为 0.05 例/1000 人年（95%CI，-0.03 至 0.16）。自杀死亡和非致命性自残的 HR 为 0.83（95%CI，0.70-0.97），新发抑郁和焦虑相关障碍的 HR 为 1.01（95%CI，0.97-1.06）。
这项队列研究主要纳入了 2 型糖尿病患者，结果并未显示 GLP-1 受体激动剂的使用与自杀死亡、自残或新发抑郁和焦虑相关障碍风险增加之间存在关联。GLP-1 受体激动剂使用者的自杀死亡罕见，置信区间上限与每年每 1000 人增加不超过 0.16 例的绝对风险增加相一致。
