Semaglutide Linked to Lower Suicidality Risk in Diabetes, With Mark Taylor, MD

New data suggest glucagon-like peptide-1 (GLP-1) receptor agonists, particularly semaglutide, are associated with lower risks of anxiety and suicidality in patients with type 2 diabetes.1,2 This contradicts prior concerns raised by the US Food and Drug Administration (FDA) regarding a potential link between GLP-1 therapies and suicidal ideation.3 The FDA could not find evidence of this association after an investigation.

“If I were a GP or a diabetologist in the States, I'd be seriously looking at the results [of] this study to inform my choices,” 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, told HCPLive. “It is quite a powerful result, albeit a correlative or associative result rather than a definitive causality result.”

The Swedish registry-based analysis included 95,490 individuals with depression or anxiety who were prescribed antidiabetic medications between 2009 and 2022.1 Using a within-individual design to minimize confounding, investigators compared periods of GLP-1 receptor agonist use with non-use in the same patients.

Semaglutide was associated with a 42% reduced risk of worsening mental illness (adjusted hazard ratio [aHR], 0.58; 95% CI, 0.51 – 0.65), while liraglutide showed a more modest benefit (aHR, 0.82; 95% CI, 0.76–0.89). No significant associations were observed for exenatide or dulaglutide.1

Secondary outcomes further supported semaglutide’s potential psychiatric benefit, including reduced risks of worsening depression (aHR, 0.56), anxiety (aHR, 0.62), and substance use disorder (aHR, 0.53). At the class level, GLP-1 receptor agonists were also associated with a lower risk of self-harm (aHR, 0.56).1

“Within the GLP [class], semaglutide comes out as a clear winner,” Taylor said.

Taylor emphasized that the observed benefits are likely multifactorial. While improved metabolic health may contribute, emerging evidence suggests potential direct central nervous system effects.

“There does appear to be a central effect to a brain effect, and we're not quite sure what the mechanism of that is,” he said.

Taylor said randomized controlled trials are needed to better understand the relationship between GLP-1s and psychiatric health, but they are expensive and difficult to organize. He said it would be helpful to compare Zepbound or Mounjaro to semaglutide or assess correlations on dose response.

“Is a higher dose of a GLP one going to be more effective or not? We don't know that yet,” Taylor said.

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. Taylor, M. GLP-1s Linked to Reduced Anxiety, Suicidality, With Mark Taylor, MD. HCPLive. Published March 21, 2026. Accessed March 24, 2026. https://www.hcplive.com/view/glp-1-receptor-agonists-linked-reduced-anxiety-suicidality-mark-taylor-md

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