Liraglutide for the Treatment of Antipsychotic Drug-Induced Weight Gain—Reply

Fink-Jensen, Anders; Correll, Christoph U.; Vilsbøll, Tina

doi:10.1001/jamapsychiatry.2017.2702

Cited by 5 publications

(3 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Liraglutide has not been detected to cause drug interactions with antipsychotic medication used for schizophrenia (55), and in this study no change in CGI-S or SQLS was found during the intervention period (39) nor at the follow-up.…”

Section: Accepted Articlementioning

confidence: 47%

One‐year follow‐up on liraglutide treatment for prediabetes and overweight/obesity in clozapine‐ or olanzapine‐treated patients

Svensson

Larsen

Vedtofte

et al. 2018

Acta Psychiatr Scand

View full text Add to dashboard Cite

Objective: Treatment with most antipsychotics is associated with an increased risk of weight gain and metabolic disturbances. In a randomized trial, we previously demonstrated that 16 weeks of glucagon-like peptide-1 receptor agonist liraglutide treatment vs. placebo significantly reduced glucometabolic disturbances and body weight in prediabetic, overweight/obese schizophrenia-spectrum disorder patients treated with clozapine or olanzapine. The aim of this study was to investigate whether the beneficial effects of the 16week intervention were sustained beyond the intervention period. Method: One year after completion of the intervention, we investigated changes in body weight, fasting glucose, glycated hemoglobin, C-peptide and lipids comparing one-year follow-up levels to end of treatment (week 16) and baseline (week 0) levels. Results: From end of treatment to the one-year follow-up, body weight had increased in the liraglutide-treated group. However, compared to baseline levels, the placebo-subtracted body weight loss remained significantly reduced (-3.8 kg, 95% CI:-7.3 to-0.2, P = 0.04). Fasting glucose, glycated hemoglobin, C-peptide and lipids had each returned to baseline levels one year after stopping liraglutide.

show abstract

Section: Accepted Articlementioning

confidence: 47%

One‐year follow‐up on liraglutide treatment for prediabetes and overweight/obesity in clozapine‐ or olanzapine‐treated patients

Svensson

Larsen

Vedtofte

et al. 2018

Acta Psychiatr Scand

View full text Add to dashboard Cite

show abstract

“…However, little is known about the molecular mechanisms by which APs induce hyperphagia. Previous studies have relied on non-specific anti-obesity drugs that suppress basal feeding to reduce AP-induced weight gain (i.e., locaserin [ 30 ], orlistat [ 31 ], liraglutide [ 32 ], nizatidine [ 33 ] metformin [ 34 ]). While using anti-obesity drugs in combination with APs is clinically beneficial to offset weight gain, they do not shed light on the specific mechanisms underlying AP-induced hyperphagia.…”

Section: Introductionmentioning

confidence: 99%

Nuclear receptor 5A2 regulation of Agrp underlies olanzapine-induced hyperphagia

et al. 2023

View full text Add to dashboard Cite

Antipsychotic (AP) drugs are efficacious treatments for various psychiatric disorders, but excessive weight gain and subsequent development of metabolic disease remain serious side effects of their use. Increased food intake leads to AP-induced weight gain, but the underlying molecular mechanisms remain unknown. In previous studies, we identified the neuropeptide Agrp and the transcription factor nuclear receptor subfamily 5 group A member 2 (Nr5a2) as significantly upregulated genes in the hypothalamus following AP-induced hyperphagia. While Agrp is expressed specifically in the arcuate nucleus of the hypothalamus and plays a critical role in appetite stimulation, Nr5a2 is expressed in both the CNS and periphery, but its role in food intake behaviors remains unknown. In this study, we investigated the role of hypothalamic Nr5a2 in AP-induced hyperphagia and weight gain. In hypothalamic cell lines, olanzapine treatment resulted in a dose-dependent increase in gene expression of Nr5a2 and Agrp. In mice, the pharmacological inhibition of NR5A2 decreased olanzapine-induced hyperphagia and weight gain, while the knockdown of Nr5a2 in the arcuate nucleus partially reversed olanzapine-induced hyperphagia. Chromatin-immunoprecipitation studies showed for the first time that NR5A2 directly binds to the Agrp promoter region. Lastly, the analysis of single-cell RNA seq data confirms that Nr5a2 and Agrp are co-expressed in a subset of neurons in the arcuate nucleus. In summary, we identify Nr5a2 as a key mechanistic driver of AP-induced food intake. These findings can inform future clinical development of APs that do not activate hyperphagia and weight gain.

show abstract

“…Previous studies have relied on non-specific anti-obesity drugs that suppress basal feeding to reduce AP-induced weight gain (i.e. locaserin 31 , orlistat 32 , liraglutide 33 , nizatidine 34 metformin 35 ). While using anti-obesity drugs in combination with APs is clinically beneficial to offset weight gain, they do not shed light on the specific mechanisms underlying AP-induced hyperphagia.…”

Section: Introductionmentioning

confidence: 99%

Nuclear Receptor 5A2 Regulation of Agrp underlies Olanzapine-induced Hyperphagia

Zapata

Zhang

Libster

et al. 2022

Preprint

View full text Add to dashboard Cite

Antipsychotic (AP) drugs are highly efficacious treatments for psychiatric disorders, but a serious side effect of their use is excessive weight gain and subsequent development of metabolic disease. Increased food intake is the underlying driver of AP-induced weight gain, although the underlying mechanisms remain unknown. In previous studies, we identified hypothalamic genes whose expression level was altered following APs-induced hyperphagia. Among these genes, the orexigenic peptide Agrp and the transcription factor nuclear receptor subfamily 5 group A member 2 (Nr5a2) were two of the most significantly upregulated genes by APs. NR5a2 is broadly expressed throughout the body, but little is known about its role in the brain. In this study, we investigated the role of hypothalamic NR5a2 in AP-induced hyperphagia and weight gain. In hypothalamic cell lines, OLZ treatment resulted in a dose-dependent increase in gene expression of NR5a2 and Agrp. In mice, administration of a specific Nr5a2 inhibitor decreased olanzapine-induced hyperphagia and weight gain, while knockdown of Nr5a2 in the arcuate nucleus (ARC) partially reversed olanzapine-induced hyperphagia. Chromatin-immunoprecipitation-PCR studies showed for the first time that NR5a2 directly binds to the Agrp promoter region. In addition, in situ hybridization studies confirm that NR5a2 and Agrp are co-localized in a subset of cells in the arcuate nucleus. In summary, we identify Nr5a2 as a key mechanistic driver of AP-induced food intake and these findings can be used to inform future clinical development of APs that do not activate hyperphagia and weight gain.

show abstract

Liraglutide for the Treatment of Antipsychotic Drug-Induced Weight Gain—Reply

Abstract: Dr Hasin reports serving as the principal investigator of a study on a measure of addiction to prescription opioids funded by InVentive Health Consulting, which combines support from 9 pharmaceutical companies. No other disclosures were reported.

Cited by 5 publications

References 5 publications

One‐year follow‐up on liraglutide treatment for prediabetes and overweight/obesity in clozapine‐ or olanzapine‐treated patients

One‐year follow‐up on liraglutide treatment for prediabetes and overweight/obesity in clozapine‐ or olanzapine‐treated patients

Nuclear receptor 5A2 regulation of Agrp underlies olanzapine-induced hyperphagia

Nuclear Receptor 5A2 Regulation of Agrp underlies Olanzapine-induced Hyperphagia

Contact Info

Product

Resources

About