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<p>The European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) have raised concerns about a potential link between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and suicide or suicide attempts. We conducted two new-user, active comparator cohort studies. The GLP1-RAs vs sodium-glucose cotransporter-2 (SGLT-2) inhibitors cohort included new users of GLP-1 RAs (<i>n</i> = <i>83,464</i>) or SGLT-2 inhibitors (<i>n</i> = <i>78,366</i>), and the GLP1-RAs vs dipeptidyl peptidase-4 (DPP-4) inhibitors cohort included new users of GLP-1 RAs (<i>n</i> = <i>108,322</i>) or DPP-4 inhibitors (<i>n</i> = <i>55,411</i>). We also employed a self-controlled case series design to compare suicide, or suicide attempts before and after GLP-1 RA treatment initiation across three time periods. In the cohort analyses patients who initiated GLP-1 RAs did not differ in the hazard ratio (HR) for suicide or suicide attempts from SGLT-2 inhibitor users (HR: 0.93; 95% CI: 0.57–1.52), and GLP-1 RA users had a lower risk of suicide or suicide attempts compared with DPP-4 inhibitor users (HR: 0.58; 95% CI: 0.37–0.91). In the self-controlled case series design, use of GLP-1 RAs was associated with a lower incidence rate ratio (IRR) of suicide or suicide attempts one year after treatment initiation (IRR: 0.45; 95% CI: 0.10–0.50) and 13–24 months after treatment initiation compared with pretreatment. This study showed that use of GLP-1 RAs was not associated with increased incidence of suicide or suicide attempts in either the active comparator new-user design or in the self-controlled case series design.</p>

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GLP-1 receptor agonists and risk of suicide or suicide attempts – A nationwide cohort and self-controlled case series study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月18日

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  • Christoffer Stanislaus,
  • Matilde Winther-Jensen,
  • Sharleny Stanislaus,
  • Merete Osler,
  • Klara Coello,
  • Maj Vinberg

摘要

The European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) have raised concerns about a potential link between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and suicide or suicide attempts. We conducted two new-user, active comparator cohort studies. The GLP1-RAs vs sodium-glucose cotransporter-2 (SGLT-2) inhibitors cohort included new users of GLP-1 RAs (n = 83,464) or SGLT-2 inhibitors (n = 78,366), and the GLP1-RAs vs dipeptidyl peptidase-4 (DPP-4) inhibitors cohort included new users of GLP-1 RAs (n = 108,322) or DPP-4 inhibitors (n = 55,411). We also employed a self-controlled case series design to compare suicide, or suicide attempts before and after GLP-1 RA treatment initiation across three time periods. In the cohort analyses patients who initiated GLP-1 RAs did not differ in the hazard ratio (HR) for suicide or suicide attempts from SGLT-2 inhibitor users (HR: 0.93; 95% CI: 0.57–1.52), and GLP-1 RA users had a lower risk of suicide or suicide attempts compared with DPP-4 inhibitor users (HR: 0.58; 95% CI: 0.37–0.91). In the self-controlled case series design, use of GLP-1 RAs was associated with a lower incidence rate ratio (IRR) of suicide or suicide attempts one year after treatment initiation (IRR: 0.45; 95% CI: 0.10–0.50) and 13–24 months after treatment initiation compared with pretreatment. This study showed that use of GLP-1 RAs was not associated with increased incidence of suicide or suicide attempts in either the active comparator new-user design or in the self-controlled case series design.