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 language | English |
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Article number | sgaa044 |
Journal | Schizophrenia Bulletin Open |
Volume | 1 |
Issue number | 1 |
Number of pages | 11 |
DOIs | |
Publication status | Published - 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.
- adiponectin, biomarker, GLP-1RA, liraglutide, OGTT, prediabetes
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