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GLP-1s Linked to Reduced Anxiety, Suicidality, With Mark Taylor, MD

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New study finds GLP-1 RAs are associated with lower anxiety, suicidality, and sick leave in patients with diabetes and mental illness.

New real-world evidence suggests GLP-1 receptor agonists may present mental health benefits in patients with type 2 diabetes, including reduced anxiety, suicidality, and functional impairment.1

“We’re not trying to say that GLP-1s are antidepressant or anti-anxiety drugs, even though they do cross the blood brain barrier and appear to have central effects, but in people with depression and anxiety, in people with type 2 diabetes, particularly, this is going to be a useful, dually effective therapeutic option,” said Mark Taylor, MD, a consultant psychiatrist from The Edinburgh Practice and a professor in the school of medicine and dentistry at Griffith University in Australia, in an interview with HCPLive.

Taylor explained that he and his colleagues conducted the study to address prior safety concerns raised by the US Food and Drug Administration (FDA) regarding potential associations between GLP-1 therapies and suicidal ideation. In August 2024, a JAMA study suggested that semaglutide may be linked to increased suicidal ideation reported; 107 on semaglutide and 162 on liraglutide reported suicidal ideation or self-harm.2 The study only detected significant disproportionality for semaglutide-associated suicidal ideation, not with liraglutide.

The 2024 study led the FDA to investigate the link between GLP-1s and suicidal ideation.3 After months of evaluation, the agency did not find evidence that any GLP-1s cause suicidal thoughts or actions. The clinical trials show that only a small portion of participants experience suicidal ideation when on GLP-1s; suicidal ideation could be influenced by other factors.

Using nationwide Swedish registry data, investigators applied a within-individual study design, comparing periods when the same patient was receiving a GLP-1 receptor agonist versus periods without treatment.1 This approach helps reduce confounding by indication and selection bias, strengthening the validity of observed associations relative to traditional cohort analyses. As Taylor explained, each individual was their “own control.”

Across multiple real-world endpoints, including hospitalization, sick leave, self-harm, and suicide, the findings pointed toward consistent psychiatric benefit rather than harm. GLP-1 receptor agonist use was associated with reduced suicidality, countering earlier safety concerns.

Two outcomes stood out clinically: reductions in psychiatric-related sick leave and lower rates of suicidal behavior.

“Mental health is now pretty much the most common reason people take time off work for health,” he noted.

The analysis did not suggest a uniform class effect. Among individual agents, semaglutide demonstrated the most pronounced benefit, including an approximately 40% reduction in depression-related outcomes and a 42% reduction in hospitalization risk during treatment periods compared with nonuse.

“This is a powerful effect,” Taylor said. “Even as authors, we were surprised by the size of this effect.”

Other GLP-1 receptor agonists showed more modest or no effect. Liraglutide demonstrated intermediate benefit, while exenatide and dulaglutide were not associated with significant improvements in psychiatric outcomes.

“There's something going on there about semaglutide that makes it more potent than, for example, liraglutide,” Taylor said. “Now, I know a lot of folks in America are using Mounjaro or Zepbound. We didn't have enough patients in the database thus far to be able to bring that into the analysis.”

References

  1. Taipale H, Taylor M, Markku Lähteenvuo, Ellenor Mittendorfer-Rutz, Antti Tanskanen, Jari Tiihonen. Association between GLP-1 receptor agonist use and worsening mental illness in people with depression and anxiety in Sweden: a national cohort study. The Lancet Psychiatry. 2026;13(4):327-335. doi:https://doi.org/10.1016/S2215-0366(26)00014-3
  2. Derman C. Semaglutide Linked to Suicidal Ideation, New Study Reveals. HCPLive. Published August 23, 2024. Accessed March 20, 2026. https://www.hcplive.com/view/semaglutide-linked-to-suicidal-ideation-new-study-reveals
  3. Update on FDA’s ongoing evaluation of reports of suicidal thoughts or actions in patients taking a certain type of medicines approved for type 2 diabetes and obesity. US Food & Drug Administration. Published January 13, 2026. Accessed March 20, 2026. https://www.fda.gov/drugs/drug-safety-and-availability/update-fdas-ongoing-evaluation-reports-suicidal-thoughts-or-actions-patients-taking-certain-type



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