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Schizophrenia Bulletin Open, 2020

DOI: 10.1093/schizbullopen/sgaa044



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Leptin serum levels are associated with GLP-1 receptor agonist-mediated effects on glucose metabolism in clozapine- or olanzapine-treated, prediabetic, schizophrenia patients

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Abstract Background We previously demonstrated that the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide significantly reduced glucometabolic disturbances and body weight vs. placebo in prediabetic, overweight or obese schizophrenia-spectrum disorder patients treated with clozapine or olanzapine. Here, we aimed to identify potential biomarkers of prediabetes and the GLP-1RA-induced effects on glucose tolerance in schizophrenia patients treated with clozapine or olanzapine Methods Multiplexed immunoassays were used to measure eight proteins (adiponectin, C-reactive protein, interleukin-1 receptor antagonist, leptin, macrophage migration inhibitory factor, prolactin, receptor for advanced glycation end products, and vascular endothelial growth factor (VEGF)) in fasting prediabetic and non-prediabetic patients with schizophrenia-spectrum disorder, the prediabetic patients receiving 16-week randomized treatment with liraglutide or placebo Results Serum adiponectin (P=0.004) and VEGF (P=0.019) levels were significantly lower in prediabetic (n=81) than non-prediabetic schizophrenia-spectrum disorder patients (n=32). Adiponectin levels increased significantly (P=0.022) and leptin levels decreased significantly (P=0.017) following treatment with liraglutide (n=39) vs. placebo (n=42). Importantly, patients receiving liraglutide who had higher baseline leptin levels showed significantly larger reductions in the primary endpoint, the 75-g oral glucose tolerance test value, than patients with lower baseline leptin levels (P=0.009) Conclusion These results provide new evidence for metabolic alterations associated with prediabetes and GLP-1RA treatment in the context of schizophrenia. They suggest that leptin may be a valuable biomarker predicting GLP-1RA-induced improvement in glucose tolerance in overweight or obese schizophrenia-spectrum disorder patients with prediabetes treated with clozapine or olanzapine. These findings require further validation in larger numbers of individuals.