Leptin Serum Levels are Associated With GLP-1 Receptor Agonist-Mediated Effects on Glucose Metabolism in Clozapine- or Olanzapine-Treated, Prediabetic, Schizophrenia Patients. Issue 1 (14th September 2020)

• Record Type: Journal Article
• Authors: Tomasik, Jakub; Rustogi, Nitin; Larsen, Julie R; Jakobsen, Michelle I; Svensson, Camilla K; Vedtofte, Louise; Jakobsen, Mathilde S L; Jespersen, Hans R; Koyuncu, Kamuran; Schjerning, Ole; Nielsen, Jimmi; Ekstrøm, Claus T; Correll, Christoph U; Holst, Jens J; Vilsbøll, Tina; Bahn, Sabine; Fink-Jensen, Anders
• Is Part Of: Schizophrenia bulletin open. Volume 1:Issue 1(2020)
• Publication Date: 2020-09-14
• Subjects: adiponectin -- biomarker -- GLP-1RA -- liraglutide -- OGTT -- prediabetes; Schizophrenia -- Periodicals; Schizophrenia -- Research -- Periodicals; Psychoses -- Periodicals; 616.898005
• DOI: 10.1093/schizbullopen/sgaa044
• Languages: English
• ISSNs: 2632-7899

Abstract

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 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.