Effect of liraglutide 3.0mg treatment on weight reduction in obese antipsychotic-treated patients

https://doi.org/10.1016/j.psychres.2021.113830Get rights and content

Highlights

  • Liraglutide 3.0mg reduces body weight of anipsychotic-treated obese patients.

  • Liraglutide improves metabolic parameters of antipsychotic-treated obese patients.

  • Treatment with liraglutide does not aggravate psychiatric symptom scores.

Abstract

Background

Patients treated with antipsychotics experience significant weight gain and accompanying metabolic disorders. We investigated the efficacy of liraglutide 3.0 mg in reducing the weight of antipsychotic-treated obese patients.

Method

We retrospectively reviewed 16 obese patients with schizophrenia or bipolar disorder who were treated with 3.0 mg of liraglutide each. During the 16 weeks of treatment, changes in body weight and Clinical Global Impression-Severity scale (CGI-S) were analyzed. The participants were divided into responders (lost at least 5% of body weight) and non-responders for analysis.

Results

Treatment with liraglutide 3.0 mg significantly decreased body weight (estimated marginal mean, 93.2 kg at baseline and 88.9 kg at 16 weeks; p < 0.001) as well as waist circumference, BMI and plasma glucose levels. Six of 16 patients (37.5%) complained of a modest degree of nausea. Six of the 12 subjects (50%) completing 16 weeks of treatment were responders. There were no significant differences in baseline characteristics between responders and non-responders. There was no worsening of CGI-S scores.

Conclusion

Liraglutide 3.0 mg significantly decreased body weight in obese patients treated with antipsychotics without altering the status of psychiatric diseases. A randomized controlled study is required to corroborate the results of this study.

Introduction

Second-generation antipsychotics are currently used as major therapeutic agents for the treatment of schizophrenia as well as bipolar disorder (Leucht et al., 2009; Rhee et al., 2020) and are recommended for continuous, long-term use unless medically contraindicated (Glick et al., 2020; Greene et al., 2018). However, patients treated with these agents are likely to gain body weight and develop metabolic disorders (Mitchell et al., 2013; Firth et al., 2019), which raises concerns about their long-term use and poor treatment adherence (Dayabandara et al., 2017; Glick et al., 2020; Greene et al., 2018).

Patients with mental illness have reduced access to health care, resulting in increased health disparities (Firth et al., 2019). Although a variety of clinical trials have assessed the effectiveness of pharmacological and non-pharmacological interventions (Vancampfort et al., 2019) in managing antipsychotic-induced weight gain (AIWG), current evidence is limited, and further studies are necessary for satisfactory results (Cooper et al., 2016; Holt, 2019). In addition, recent guidelines for the management of obesity recommend against the use of lorcaserin, phentermine/topiramate, or naltrexone/bupropion, which are anti-obesity drugs used by the general population, to treat obese patients with psychoses because of safety concerns (Garvey et al., 2016).

Glucagon-like peptide-1 receptor agonist (GLP-1 RA) induces weight loss mainly via effects on appetite and satiety (Janssen et al., 2013). Interestingly, preclinical mechanistic studies suggest that antipsychotics reduce the levels of active GLP-1 (Smith et al., 2009; Smith et al., 2011), which implies a synergistic effect of GLP-1 RA in treating AIWG. To date, only three studies have reported the effect of GLP-1 RA on weight reduction in antipsychotic-treated patients, including two studies using exenatide, and one study investigating liraglutide (Ishoy et al., 2017; Larsen et al., 2017; Siskind et al., 2018). Among the studies using exenatide, Siskind et al. (Siskind et al., 2018) demonstrated significantly greater weight reduction in the exenatide group than in the placebo group, whereas Ishøy et al., (Ishoy et al., 2017) did not, prompting additional clinical trials. Liraglutide is a potent GLP-1 RA and a potential treatment for both obesity and type 2 diabetes depending upon the dose (3.0 mg for obesity and 1.8 mg for diabetes). Favorable effects of liraglutide were found in patients with antipsychotic-associated metabolic disorders using a maximum dose of 1.8 mg based on changes in glucose tolerance as the primary outcome (Larsen et al., 2017). The effect of 3.0 mg of liraglutide on obese antipsychotic-treated patients has yet to be evaluated, except that a clinical trial protocol proposed the use of a maximum dosage of 3 mg to induce greater weight loss compared with 1.8 mg in patients with severe mental illness (Whicher et al., 2019). Thus, in this study, we investigated the effect of liraglutide 3.0 mg on the body weight of antipsychotic-treated patients.

Section snippets

Study design and population

This study was a retrospective chart review of a cohort of 16 obese patients taking antipsychotics, who received a liraglutide dose of 3.0 mg each between June 2018 and April 2019 at Dongguk University Ilsan Hospital, Goyang, Korea. A descriptive exploratory design was used to examine the effect of liraglutide 3.0 mg on the body weight of antipsychotic-treated patients without a control group. The psychiatric diseases in this study included schizophrenia and bipolar disorder. Patients with a

Results

Sixteen patients with schizophrenia or bipolar disorder were treated with 3.0 mg liraglutide. Their baseline characteristics are shown in Table 1. The patients’ mean age was 37.8 years and 43.8% of the participants were men. All of the 16 patients were taking antipsychotics, including 14 undergoing treatment with clozapine. Three patients were taking antipsychotic monotherapy (two with clozapine and one with paliperidone palmitate), and the remaining patients were prescribed two or more

Discussion

This was the first study to show the effects of treatment with 3.0 mg of liraglutide on obese antipsychotic-treated patients. Sixteen weeks of treatment with liraglutide significantly reduced body weight and associated cardiometabolic risk factors. Notably, no treatment-related differences were found with respect to the severity of the psychiatric diseases. The safety and tolerability of liraglutide 3.0 mg were also investigated in this population. Nausea was the most common side effect.

Author statement

Conceptualization: Young Sik Kim, Kyoung-Ah Kim

Methodology: Seung Eun Lee, Nam Young Lee, Se Hyun Kim, Kyoung-Ah Kim, Yong Sik Kim

Software: Seung Eun Lee

Validation: Nam Young Lee, Se Hyun Kim, Yong Sik Kim

Formal analysis: Seung Eun Lee

Investigation: Seung Eun Lee, Nam Young Lee, Se Hyun Kim

Resources: Kyoung-Ah Kim, Yong Sik Kim

Data Curation: Seung Eun Lee, Nam Young Lee, Se Hyun Kim

Writing - Original Draft: Seung Eun Lee, Yong Sik Kim

Writing - Review & Editing: Nam Young Lee, Kyoung-Ah Kim,

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgment

This study was not funded by any agency in the public, commercial, or not-for-profit sectors.

References (58)

  • K. Katsurada et al.

    Endogenous GLP-1 acts on paraventricular nucleus to suppress feeding: projection from nucleus tractus solitarius and activation of corticotropin-releasing hormone, nesfatin-1 and oxytocin neurons

    Biochem. Biophys. Res. Commun.

    (2014)
  • X.M. Li et al.

    Evidence for neuroprotective effects of antipsychotic drugs: implications for the pathophysiology and treatment of schizophrenia

    Int. Rev. Neurobiol.

    (2007)
  • G.C. Smith et al.

    Clozapine and quetiapine acutely reduce glucagon-like peptide-1 production and increase glucagon release in obese rats: implications for glucose metabolism and food choice behaviour

    Schizophr. Res.

    (2009)
  • L.L. Baggio et al.

    Glucagon-like peptide-1 receptors in the brain: controlling food intake and body weight

    J. Clin. Invest.

    (2014)
  • A. Blackman et al.

    Effect of liraglutide 3.0 mg in individuals with obesity and moderate or severe obstructive sleep apnea: the SCALE Sleep Apnea randomized clinical trial

    Int. J. Obes. (Lond.)

    (2016)
  • M.A. Camkurt et al.

    Liraglutide for psychiatric disorders: clinical evidence and challenges

    Horm. Mol. Biol. Clin. Investig.

    (2018)
  • C. Cercato et al.

    Cardiovascular risk and obesity

    Diabetol. Metab. Syndr.

    (2019)
  • C.W. Chia et al.

    Incretins in obesity and diabetes

    Ann. N. Y. Acad. Sci.

    (2020)
  • S.J. Cooper et al.

    BAP guidelines on the management of weight gain, metabolic disturbances and cardiovascular risk associated with psychosis and antipsychotic drug treatment

    J. Psychopharmacol.

    (2016)
  • M. Dayabandara et al.

    Antipsychotic-associated weight gain: management strategies and impact on treatment adherence

    Neuropsychiatr. Dis. Treat.

    (2017)
  • J. Firth et al.

    Aerobic exercise improves cognitive functioning in people with schizophrenia: a systematic review and meta-analysis

    Schizophr. Bull.

    (2017)
  • K. Fujioka et al.

    Early weight loss with liraglutide 3.0 mg predicts 1-year weight loss and is associated with improvements in clinical markers

    Obesity (Silver Spring)

    (2016)
  • I.D. Glick et al.

    Are patients with schizophrenia better off with lifetime antipsychotic medication?: Replication of a naturalistic, long-term, follow-up study of antipsychotic treatment

    J. Clin. Psychopharmacol.

    (2020)
  • M. Greene et al.

    Systematic literature review on patterns of pharmacological treatment and adherence among patients with bipolar disorder type I in the USA

    Neuropsychiatr. Dis. Treat.

    (2018)
  • S.M. Grundy et al.

    Diagnosis and management of the metabolic syndrome: an American heart association/national heart, lung, and blood institute scientific statement

    Circulation

    (2005)
  • F. Guaraldi et al.

    Predictors of weight loss and maintenance in patients treated with antiobesity drugs

    Diabetes Metab. Syndr. Obes.

    (2011)
  • Guy, W., 1976. ECDEU assessment manual for psychopharmacology, revised (DHEW Publ No ADM 76-338)....
  • R.I.G. Holt

    The management of obesity in people with severe mental illness: an unresolved conundrum

    Psychother. Psychosom.

    (2019)
  • K. Hunter et al.

    Drugs developed to treat diabetes, liraglutide and lixisenatide, cross the blood brain barrier and enhance neurogenesis

    BMC Neurosci.

    (2012)
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