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Scientists comment on a study, published in The Lancet Psychiatry, linking GLP-1s to reduced need for acute psychiatric care for patients with schizophrenia and type 2 diabetes.
Dr Jon van Niekerk, Chair of the Faculty of General Adult Psychiatry at the Royal College of Psychiatrists said:
“This is an interesting and potentially important study, particularly given the substantial physical health inequalities experienced by people living with schizophrenia. The possibility that medications used to improve metabolic health might also be associated with better psychiatric outcomes deserves serious attention.
“The large study population, the use of routinely collected clinical data and, importantly, comparisons with other diabetes medications are strengths. The reported reductions in psychiatric admissions and emergency mental health care are clinically meaningful outcomes, although the study cannot establish that GLP-1 medications directly improve psychiatric symptoms or prevent relapse.
“One important consideration is whether the researchers have adequately accounted for differences in psychiatric illness severity, antipsychotic prescribing and engagement with healthcare. For example, patients established on clozapine or other antipsychotics associated with significant metabolic complications may be more likely to receive GLP-1 treatment, but their underlying psychiatric stability and risk of admission may differ substantially from other patients. These factors are difficult to account for fully in observational research.
“The finding that the association persists among people who did not lose weight is intriguing and raises questions about possible mechanisms beyond weight reduction. However, this does not establish a direct effect on schizophrenia itself.
“These findings are consistent with a growing body of observational research suggesting potential psychiatric benefits associated with some GLP-1 medications. However, randomised evidence has not yet demonstrated a clear improvement in psychotic symptoms. The distinction between reduced use of acute psychiatric services and improvement in the underlying illness is important.
“Overall, this is promising research that strengthens the case for further investigation, ideally through randomised trials. It also reinforces the importance of addressing physical and mental health together. However, it would be premature to regard GLP-1 medications as treatments for schizophrenia or to change psychiatric prescribing practice on the basis of these findings alone.”
Dr Riccardo De Giorgi, Senior Clinical Researcher and Honorary Consultant in General Adult Psychiatry, Department of Psychiatry, University of Oxford, said:
“This is a large, well-conducted observational study, and both the paper and press release are appropriately cautious. The NeuroBlu dataset allows unusually detailed adjustment for psychiatric treatment, including antipsychotic use, metabolic-risk category, and route of administration – which matters because these can be obvious sources of confounding. The headline results are interesting, but perhaps more nuanced than a simple protective association. Associations were clearest in younger people and those taking antipsychotics, and were less consistent in several other subgroups. The reporting regarding weight loss also deserves caution: the association was strongest in people who lost weight and persisted with stable weight in some comparisons, but not consistently in those who gained weight. This raises the possibility of benefits beyond weight loss, but still cannot demonstrate a weight-independent psychiatric effect.
“The main limitation is, as always with such designs, residual confounding. Importantly, prescribing GLP-1s may identify patients who differ in healthcare engagement or clinical profile in ways that electronic health record (EHR) adjustment cannot capture. Overall, I think these findings extend existing evidence: they provide a further signal that GLP-1 treatment may have benefits beyond metabolic health in people with schizophrenia and diabetes, but they cannot yet show that GLP-1 drugs prevent relapse or act as psychiatric treatments. That question now needs a randomised controlled trial.”
Prof Joseph Firth, Professor of Psychology & Mental Health, University of Manchester, said:
“One of the most striking and overlooked side-effects of antipsychotic medications is the increased appetite, and reductions in satiety, among people treated with these medications. For some, this can make it feel almost impossible to adhere to a healthy diet (or manage bodyweight), and in turn result in self-discontinuation of the medications, which is a common preceding factor to relapse / hospitalisation. Interestingly, GLP-1 RAs seem to act particularly quickly and powerfully to regulate appetite/satiety pathways, which could cancel out most of the downsides of antipsychotics in this single domain. So, it does make sense that using GLP-1 RAs in an evidence-based manner could help to not only tackle some of the most damaging side-effects of antipsychotics physically, but also, in doing so, help people to continue adhering to their course of psychiatric treatment and thus experience less need for acute care or hospitalisation in future.
“The current limitation is this novel field of research is the observational nature of the studies to date, which prevents any causal conclusions, but does pave the way for lots of interesting theories and further research to explore this in future. In particular, it will be critical to establish if and how far the findings replicate across other psychiatric samples, and what the key driving factors are – be it medication adherence or otherwise – in order to learn how best to use these new treatments in conjunction with other pharmacological and behaviour strategies to enhance both physical and mental health outcomes”
Dr Sameer Jauhar, Clinical Associate Professor in Affective Disorders and Psychosis, Imperial College London, said:
“GLP-1 receptor agonists have rapidly entered the collective consciousness of those working in healthcare, with apparent benefits extending well beyond blood sugar control — weight, cardiovascular risk, alcohol consumption, and now, potentially, psychiatric outcomes in schizophrenia. This paper analyses US health record data from over 70,000 people with both schizophrenia and type 2 diabetes and finds that those prescribed GLP-1 medications were less likely to be admitted to a psychiatric hospital or attend an emergency department for a mental health crisis, an association that held up against other active diabetes medications, not only against no treatment. This lends the finding some credibility.
“Pertinently, people with schizophrenia have historically had poor access to these medications, despite carrying a disproportionate metabolic burden, and much of it is attributable to antipsychotic medication, which remains central to managing the illness. Findings like these should prompt clinicians and commissioners to think carefully about that disparity.
“But do these drugs actually improve psychiatric outcomes? This is observational data, and the confounding is not trivial. People prescribed GLP-1 medications in the US tend to be more engaged with healthcare, have better insurance, and see more proactive clinicians — all of which independently reduce psychiatric hospitalisation regardless of what medication they are receiving. Looking at the survival curves in the paper, the groups disentangle almost immediately after treatment initiation and then remain parallel throughout follow-up, which is a pattern more consistent with pre-existing differences between groups than with a pharmacological effect, which would be expected to emerge gradually over months. The authors are appropriately cautious and should be commended for it; it would be easy to get carried away with various neurobiological theories that I would not bet my mortgage on (just yet).
“What we can conclude is that GLP-1 agonists do not appear to worsen psychiatric outcomes in this population- and that, in my view, is itself a worthwhile finding. On that basis alone, we should be advocating for better access to these medications for people with schizophrenia.”
Prof Dame Til Wykes FMedSci, Professor of Clinical Psychology and Rehabilitation, King’s College London, said:
“This is a novel and well conducted study that provides information on the relationship between weight loss drugs and psychiatric hospitalisation or emergency care, particularly for younger people. The authors acknowledge the limitations of their data and say, “The potential clinical relevance of GLP-1 receptor agonist initiation should be interpreted cautiously.” Although the authors suggest metabolic links are key to the relationship but that other factors may also be important contributors, such as increased health service contacts associated with weight loss drug use or that the group accepting these drugs were more compliant with their anti-psychotic drug regime.”
‘GLP-1 receptor agonist initiation and risk of psychiatric hospitalisation and emergency department presentation in adults with schizophrenia and type 2 diabetes in the USA: an observational cohort study using electronic health records data’ by Najmeh Davoodian et al. was published in The Lancet Psychiatry at 23:30 UK time on Wednesday 14th October.
Declared interests
Dr Jon van Niekerk: “In addition to being Chair of the Faculty of General Adult Psychiatry at the Royal College of Psychiatrists, Dr van Niekerk is the Chief Medical Officer of Elysium Healthcare. No other relevant financial or industry interests. The views expressed in this comment represent the Royal College of Psychiatrists.”
Dr Riccardo De Giorgi: “No CoI.”
Prof Joseph Firth: “I have no conflicts of interests on this subject.”
Dr Sameer Jauhar: “Sameer Jauhar has received personal fees from Recordati, LB Pharmaceuticals, Boehringer Ingelheim, Accord Pharmaceuticals, Wellcome Trust, Lundbeck, Janssen and Sunovion, and non-financial support from the National Institute for Health and Care Excellence, the British Association for Psychopharmacology and the Royal College of Psychiatrists.”
Prof Dame Til Wykes FMedSci: “I have no conflict of interest with this article.”