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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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 8 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 =. 004) and VEGF (P =. 019) levels were significantly lower in prediabetic (n = 81) than non-prediabetic schizophrenia-spectrum disorder patients (n = 32). Adiponectin levels increased significantly (P =. 022) and leptin levels decreased significantly (P =. 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 =. 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.

Original languageEnglish
Article numbersgaa044
JournalSchizophrenia Bulletin Open
Issue number1
Number of pages11
Publication statusPublished - 2020

Bibliographical note

Publisher Copyright:
© 2020 The Author(s). Published by Oxford University Press on behalf of the University of Maryland's school of medicine, Maryland Psychiatric Research Center.

    Research areas

  • adiponectin, biomarker, GLP-1RA, liraglutide, OGTT, prediabetes

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