Metabolic biomarker levels before and after initiation of GLP-1 receptor agonist treatment among individuals with schizophrenia: interrupted time-series analysis

Background Randomised controlled trials have demonstrated that treatment with glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduces body weight, waist circumference and haemoglobin A1c (HbA1c) levels in patients with schizophrenia. However, because of participant selection in clinical trials, it remains unclear whether the beneficial metabolic effects of GLP-1RAs for patients with schizophrenia extend to real-world clinical settings. Aims We investigated whether GLP-1RA treatment initiation was associated with reductions in HbA1c, low-density lipoprotein (LDL) and triglyceride levels (the latter two as proxies for weight loss) in individuals with schizophrenia. Method We used the Danish nationwide registers to identify individuals with schizophrenia between 1996 and 2023. Among those, we identified individuals initiating GLP-1RA treatment. The main outcomes were changes in HbA1c, LDL and triglyceride levels following initiation of GLP-1RA treatment. Changes in HbA1c, LDL and triglyceride levels were visualised graphically and quantified with interrupted time-series analyses. Results We identified 3042 individuals with schizophrenia who initiated a GLP-1RA. Initiation of GLP-1RA treatment for diabetes was followed by reductions in HbA1c, LDL and triglyceride levels of 11.4, 6.2 and 14.8%, respectively. Initiation of GLP-1RA treatment for overweight was followed by reductions in HbA1c, LDL and triglyceride levels of 3.4, 4.9 and 12.7%, respectively. All level changes were statistically significant ( p < 0.001). Conclusions Initiation of GLP-1RA treatment was followed by clinically meaningful reductions in HbA1c, LDL and triglyceride levels among individuals with schizophrenia. These findings suggest that the metabolic benefits of GLP-1RA treatment found in randomised clinical trials in schizophrenia extend to real-world clinical settings.