March 18, 2026

expert reaction to observational study on GLP-1 receptor agonists and lower risk of worsening mental illness, as published in The Lancet Psychiatry

experts comment on an observational study on GLP-1 receptor agonists and lower risk of worsening mental illness

Prof Ian Maidment, Professor in Clinical Pharmacy, Aston University, said:

“This research showed that the GLP-1 receptor agonists liraglutide and in particular semaglutide were associated with a lower risk of worsening mental illness in people with anxiety and depression who took medication for diabetes. Semaglutide and liraglutide were associated with a lower risk of worsening depression and semaglutide was also associated with lower risk of worsening anxiety and substance use disorder.

“There are a number of limitations with the research. Most important this is an observational study and future clinical trials are needed to confirm whether or not the GLP-1 agonists are effective treatments for disorders such as depression and anxiety. The research was conducted in a single country (Sweden) and data on ethnicity was not available. The database used for the analysis did not record individual patient data on the symptom severity, changes in weight or markers for diabetes. Overall, the study showed that certain GLP-1 agonists are associated with a lower risk of worsening mental illness, but this needs testing in full clinical trials.”

Dr Vincenzo Oliva, Post-doctoral Researcher, Institute of Biomedical Research August Pi i Sunyer, Barcelona, said:

“The study published in The Lancet Psychiatry by Taipale and colleagues examines the association between GLP-1 receptor agonist use and the risk of worsening mental illness in a large national cohort of individuals with pre-existing depression or anxiety (n=95,490). Using a within-individual design, the authors compare periods of treatment and non-treatment within the same person, and report that some GLP-1 receptor agonists, particularly semaglutide, are associated with a lower risk of worsening mental illness, including psychiatric hospitalisation, sick leave, self-harm, and death by suicide.

“These findings fit within a rapidly growing interest in GLP-1 receptor agonists as agents with potential effects beyond metabolism, including in neuropsychiatric domains. This growing interest has been accompanied by both early concerns and high expectations. Initial pharmacovigilance reports suggested a possible increase in suicidal ideation, but subsequent evidence has been reassuring. In this context, it is important to emphasise that this study focuses on “lower risk of worsening” rather than direct symptom improvement, reinforcing that the primary message remains related to safety while also cautiously raising the possibility of a beneficial effect. Notably, the authors maintain a careful and measured interpretation of their findings, avoiding overstatement despite the current level of interest surrounding these treatments.

“A particularly relevant aspect of this study is that it focuses on individuals with an established diagnosis of depression or anxiety, rather than general populations with obesity or diabetes. This strengthens the clinical relevance of the observed signal and makes the findings more directly applicable to psychiatric populations.

“More broadly, the results are consistent with the increasingly recognised link between metabolic and mental health. The fact that this signal continues to emerge across different datasets adds to its credibility, although the underlying mechanisms are likely complex and multifactorial. Interestingly, the differences observed between individual GLP-1 receptor agonists suggest that this may not simply be a class effect, but rather reflect pharmacological heterogeneity, including differences in metabolic efficacy and possibly central nervous system effects, although non-pharmacological factors such as patient selection and prescribing patterns are also likely to play a role.

Prof Eduard Vieta, Professor of Psychiatry and Chair, University of Barcelona, and European College of Neuropsychopharmacology, said:

“From a clinical perspective, these findings are reassuring regarding the psychiatric safety of GLP-1 receptor agonists and suggest a potential role not only in preventing worsening but also, possibly, in improving mental health outcomes. However, they should not yet be interpreted as evidence of a direct therapeutic effect on depression or anxiety. Although the study design reduces some sources of bias, residual confounding cannot be fully excluded, and factors such as the COVID-19 pandemic, which had a substantial impact on population mental health, may also have influenced the results. Carefully designed prospective studies and randomised controlled trials in psychiatric populations will be essential to clarify whether these associations translate into causal, meaningful clinical benefits. As with all observational studies, these findings do not establish causality.

“Finally, in my opinion the title of the paper might be misleading, as the main findings actually report a reduction of the risk of mental health worsening associated to some of those compounds. A quick reading of the title might lead to the opposite conclusion.”

Prof David Nutt, The Edmond J Safra Chair and Head of the Centre for Neuropsychopharmacology, Division of Brain Sciences, Dept of Medicine, Imperial College London, and Chair of the scientific committee of DrugScience, said:

“It is well established that better mental health tends to follow from better physical health and since the 1880s we have known that diabetes is associated with depression (https://pubmed.ncbi.nlm.nih.gov/29946211/).

“Their hypothesis that the increase in insulin may be a mechanism of action fits with observations in my work on ECT, where the increase in insulin relates to treatment outcomes (https://pubmed.ncbi.nlm.nih.gov/1638337/).

“Some of the theory behind this observation might seem plausible, although I think it’s unlikely that using GLP-1R agonists alone as treatments for depression or anxiety will work.” 

* ‘Association between GLP-1 receptor agonist use and worsening mental illness in people with depression and anxiety in Sweden: a national cohort study’ by Heidi Taipale et al. was published in The Lancet Psychiatry at 23:30 UK time on Wednesday 18^th March.

Declared interests

Prof Ian Maidment: “No conflicts of interest”

Dr Vincenzo Oliva: “Dr. Oliva has no direct conflict of interest related to this topic”

Prof Eduard Vieta: “I am an advisor of Eli Lilly as regards to their products in the pipeline including one GLP-1 agonist.”

Prof David Nutt: “DJN receives support from the UK NIHR and Solvonis therapeutics for research into psychedelic treatments of addiction.”