Effect of liraglutide 3.0mg treatment on weight reduction in obese antipsychotic-treated patients
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)
- et al.
The metabolic syndrome–a new worldwide definition
Lancet
(2005) - et al.
Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study
Lancet
(2009) - et al.
Neuroprotective effects of the second generation antipsychotics
Schizophr. Res.
(2019) - et al.
Antipsychotic-like effect of GLP-1 agonist liraglutide but not DPP-IV inhibitor sitagliptin in mouse model for psychosis
Physiol. Behav.
(2013) Mechanisms of action and therapeutic application of glucagon-like peptide-1
Cell Metab.
(2018)Predicting therapeutic weight loss
Am. J. Clin. Nutr.
(2015)- et al.
The Lancet Psychiatry Commission: a blueprint for protecting physical health in people with mental illness
Lancet Psychiatry
(2019) - et al.
Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial
Lancet
(2011) - et al.
American association of clinical endocrinologists and American college of endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity
Endocr. Pract.
(2016) - et al.
Practical use of pharmacotherapy for obesity
Gastroenterology
(2017)
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.
Evidence for neuroprotective effects of antipsychotic drugs: implications for the pathophysiology and treatment of schizophrenia
Int. Rev. Neurobiol.
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.
Glucagon-like peptide-1 receptors in the brain: controlling food intake and body weight
J. Clin. Invest.
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.)
Liraglutide for psychiatric disorders: clinical evidence and challenges
Horm. Mol. Biol. Clin. Investig.
Cardiovascular risk and obesity
Diabetol. Metab. Syndr.
Incretins in obesity and diabetes
Ann. N. Y. Acad. Sci.
BAP guidelines on the management of weight gain, metabolic disturbances and cardiovascular risk associated with psychosis and antipsychotic drug treatment
J. Psychopharmacol.
Antipsychotic-associated weight gain: management strategies and impact on treatment adherence
Neuropsychiatr. Dis. Treat.
Aerobic exercise improves cognitive functioning in people with schizophrenia: a systematic review and meta-analysis
Schizophr. Bull.
Early weight loss with liraglutide 3.0 mg predicts 1-year weight loss and is associated with improvements in clinical markers
Obesity (Silver Spring)
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.
Systematic literature review on patterns of pharmacological treatment and adherence among patients with bipolar disorder type I in the USA
Neuropsychiatr. Dis. Treat.
Diagnosis and management of the metabolic syndrome: an American heart association/national heart, lung, and blood institute scientific statement
Circulation
Predictors of weight loss and maintenance in patients treated with antiobesity drugs
Diabetes Metab. Syndr. Obes.
The management of obesity in people with severe mental illness: an unresolved conundrum
Psychother. Psychosom.
Drugs developed to treat diabetes, liraglutide and lixisenatide, cross the blood brain barrier and enhance neurogenesis
BMC Neurosci.
Cited by (12)
Eating cognitions, emotions and behaviour under treatment with second generation antipsychotics: A systematic review and meta-analysis
2023, Journal of Psychiatric ResearchGLP-1 agonists: superior for mind and body in antipsychotic-treated patients?
2022, Trends in Endocrinology and MetabolismCitation Excerpt :The total APD and GLP-1 RA-treated population included in clinical studies so far is n = 113. Specifically, one study enrolled 47 patients treated with liraglutide 1.8 mg daily [45] and another two enrolled together 31 patients treated with liraglutide 3 mg daily [46,47], while the last two of currently available trials used exenatide 2 mg weekly in 34 patients in total [48,49]. Results from these studies indicate beneficial effects of GLP-1 RAs, potentially reducing the adverse metabolic outcome of APD treatment and associated CVD risk factors in patients with schizophrenia [46,47,50,51].
A systematic review of licensed weight-loss medications in treating antipsychotic-induced weight gain and obesity in schizophrenia and psychosis
2022, General Hospital PsychiatryCitation Excerpt :Other cardiometabolic risk factors (waist circumference, systolic blood pressure, HbA1c, fasting glucose, total cholesterol, LDL) however had returned to baseline levels. These findings are supported by other observational studies [51,52,58,59]; all of which found liraglutide beneficial as previously summarised in Table 2. Likewise, Tham et al. [55] found that its liraglutide monotherapy subset of subjects (n = 87) averaged a reduction in weight of 10.9 ± 5.2% (p-value <.001) and waist circumference of 11.4 ± 5.2 cm (p-value <.01) after 52 weeks.