GLP-1 drugs linked to reduced acute schizophrenia episodes

The list of illnesses that seem to benefit from treatment with GLP-1 agonists seems to get ever longer, and a study has suggested that schizophrenia could be an addition.

An intriguing observational study published in The Lancet Psychiatry has found that people living with both type 2 diabetes (T2D) and schizophrenia who are treated with GLP-1 drugs have a reduced need for acute psychiatric care, such as hospital admissions, compared to other diabetes therapies like DPP-4 or SGLT2 inhibitors.

While the authors stress the finding is preliminary, it could be clinically significant, as many people living with schizophrenia experience persistent symptoms despite treatment with antipsychotic medicines, and they have a two- to five-fold increased risk of developing T2D compared to the general population.

Some studies have pointed to overlapping genetic risk factors that predispose individuals to both schizophrenia and insulin resistance, while various antipsychotic drugs are known to cause weight gain and other metabolic changes as side effects.

The new study looked at health records from more than 70,000 people with schizophrenia, of whom around 12.9% had been treated with GLP-1 agonists, and roughly 7% had received DPP-4 or SGLT2 inhibitors.

GLP-1 agonist treatment was associated with a 24% lower risk of psychiatric hospitalisation compared to the group that had not been treated for diabetes, and 18% and 17% lower, respectively, for those who had treatment with DPP-4 and SGLT2 inhibitors in their history. It was also associated with a reduced risk of attending emergency departments. Interestingly, the benefits seemed to accrue regardless of whether subjects lost weight.

The researchers conclude that the findings "suggest that lower psychiatric acute-care use could be a favourable secondary benefit when GLP-1-based therapies are clinically indicated for metabolic management, although their use as primary psychiatric treatments requires investigation in randomised and mechanistic studies."

"This is an interesting and potentially important study, particularly given the substantial physical health inequalities experienced by people living with schizophrenia," commented Dr Jon van Niekerk of the Royal College of Psychiatrists in the UK, who was not involved in the study.

"The possibility that medications used to improve metabolic health might also be associated with better psychiatric outcomes deserves serious attention," he added, whilst noting that the study was probably unable to take into account variables such as differences in psychiatric illness severity, antipsychotic prescribing, and engagement with healthcare systems.

"The headline results are interesting, but perhaps more nuanced than a simple protective association," added Dr Riccardo De Giorgi, of Oxford University's department of psychiatry.

"Associations were clearest in younger people and those taking antipsychotics, and were less consistent in several other subgroups," he pointed out.

"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."

Future studies should explore the role of GLP-1 agonists in schizophrenia patients, including in populations without type 2 diabetes, conclude the study authors.

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