Glucagon-like peptide-1 analogs against antipsychotic-induced weight gain: potential physiological benefits

Ebdrup, Bjørn H; Knop, Filip K.; Ishøy, Pelle L.; Rostrup, Egill; Fagerlund, Birgitte; Lublin, Henrik; Glenthøj, Birte

doi:10.1186/1741-7015-10-92

Cited by 25 publications

(24 citation statements)

References 70 publications

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“…Interestingly, GLP-1 receptor agonists also induce weight loss in both diabetic and nondiabetic patients, 48 and they may therefore be used to treat antipsychotic-induced obesity. [49][50][51] Endogenous GLP-1 levels have been reported in 2 studies 39,41 evaluating the effect of short-term olanzapine treatment in healthy subjects: Vidarsdottir et al 39 showed no effect of olanzapine, whereas Teff et al 41 recently reported increases in postprandial GLP-1 levels. To our knowledge, the present study is the first to report plasma levels of endogenous GLP-1 in patients treated with antipsychotic drugs.…”

Section: Discussionmentioning

confidence: 99%

Glucometabolic Hormones and Cardiovascular Risk Markers in Antipsychotic-Treated Patients

Ebdrup¹,

Knop²,

Madsen³

et al. 2014

J. Clin. Psychiatry

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Objective: Treatment with antipsychotic drugs is widely associated with metabolic side effects such as weight gain and disturbed glucose metabolism, but the pathophysiologic mechanisms are unclear.Method: Fifty nondiabetic (fasting plasma glucose ≤ 7.0 mmol/L), antipsychotic-treated male patients (ICD-10 diagnosis code F20, F21, F22, F25, F28, or F60; mean ± SD age = 33.0 ± 6.7 years; body mass index [BMI; kg/ m 2 ] = 26.0 ± 4.7; waist circumference = 95.9 ± 13.3 cm; glycated hemoglobin A 1c [HbA 1c ] = 5.7% ± 0.3%) and 93 age-and waist circumference-matched healthy male controls (age = 33 ± 7.3 years; BMI = 26.1 ± 3.9; waist circumference = 94.6 ± 11.9 cm; HbA 1c = 5.7% ± 0.3%) participated in this cross-sectional study. Blood was sampled in the fasting state and 90 minutes after ingestion of a standardized liquid meal (2,268 kJ). The primary outcomes were glucometabolic hormones and cardiovascular risk markers. Data were collected between March 2008 and February 2010.Results: Compared to healthy controls, patients were characterized by elevated fasting levels of proinsulin, C-peptide, and glucose-dependent insulinotropic polypeptide (GIP) (P < .05) and higher postprandial levels of insulin, proinsulin, C-peptide, and GIP (P ≤ .02). Also, patients exhibited elevated plasma levels of C-reactive protein and signs of dyslipidemia. Fasting plasma levels of insulin, glucagon, glucagon-like peptide-1 (GLP-1), ghrelin, leptin, adiponectin, tumor necrosis factor-α, plasminogen activator inhibitor-1, and interleukin-6 and postprandial levels of glucagon, GLP-1, ghrelin, leptin, and adiponectin did not differ between groups. Conclusions:Presenting with an insulin resistant-like pattern, including beta cell hypersecretion and elevated GIP levels, nondiabetic antipsychotic-treated patients display emerging signs of dysmetabolism and a compromised cardiovascular risk profile. The appetite-regulating hormones GLP-1 and ghrelin appear not to be influenced by antipsychotic treatment. Our findings provide new clinical insight into the pathophysiology associated with metabolic side effects of antipsychotic treatment and put emphasis on the importance of implementing metabolic screening into psychiatric practice.Trial Registration: ClinicalTrials.gov identifier NCT00627757 Clin Psychiatry 2014;75(9):e899-e905 J

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Section: Discussionmentioning

confidence: 99%

Glucometabolic Hormones and Cardiovascular Risk Markers in Antipsychotic-Treated Patients

Ebdrup¹,

Knop²,

Madsen³

et al. 2014

J. Clin. Psychiatry

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“…To our knowledge, this is the first clinical evidence supporting the use of GLP-1 receptor agonists in the treatment of antipsychotic-induced weight gain (2). To our knowledge, this is the first clinical evidence supporting the use of GLP-1 receptor agonists in the treatment of antipsychotic-induced weight gain (2).…”

Section: Discussionmentioning

confidence: 99%

“…Although oral naltrexone appears to be the most promising among seven therapeutic drugs investigated for gambling (1), poor adherence to oral naltrexone can be a problem (2). Although oral naltrexone appears to be the most promising among seven therapeutic drugs investigated for gambling (1), poor adherence to oral naltrexone can be a problem (2).…”

Section: Monthly Injectable Naltrexone For Pathological Gamblingmentioning

confidence: 99%

Sustained Weight Loss After Treatment With a Glucagon-Like Peptide-1 Receptor Agonist in an Obese Patient With Schizophrenia and Type 2 Diabetes

Ishøy¹,

Knop²,

Vilsbøll³

et al. 2013

AJP

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“…Recently, we suggested the GLP-1 receptor agonist therapy as a potential treatment strategy for patients with schizophrenia and obesity 10. In a subsequent case report we provided the first clinical evidence in support of this idea 14.…”

Section: Introductionmentioning

confidence: 80%

Treatment of antipsychotic-associated obesity with a GLP-1 receptor agonist—protocol for an investigator-initiated prospective, randomised, placebo-controlled, double-blinded intervention study: the TAO study protocol

et al. 2014

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IntroductionAntipsychotic medication is widely associated with dysmetabolism including obesity and type 2 diabetes, cardiovascular-related diseases and early death. Obesity is considered the single most important risk factor for cardiovascular morbidity and mortality. Interventions against antipsychotic-associated obesity are limited and insufficient. Glucagon-like peptide-1 (GLP-1) receptor agonists are approved for the treatment of type 2 diabetes, but their bodyweight-lowering effects have also been recognised in patients with non-diabetes. The primary endpoint of this trial is weight loss after 3 months of treatment with a GLP-1 receptor agonist (exenatide once weekly) in patients with non-diabetic schizophrenia with antipsychotic-associated obesity. Secondary endpoints include physiological and metabolic measurements, various psychopathological and cognitive measures, and structural and functional brain MRI.Methods and analysis40 obese patients with schizophrenia or schizoaffective disorder treated with antipsychotic drugs will be randomised to subcutaneous injection of exenatide once weekly (2 mg) or placebo for 3 months, adjunctive to their antipsychotic treatment.Ethics and disseminationThe trial has been approved by the Danish Health and Medicines Authority, the National Committee on Health Research Ethics and the Danish Data Protection Agency. Trial participation presupposes theoral and written patient informed consent. An external, independent monitoring committee (Good Clinical Practice Unit at Copenhagen University Hospital) will monitor the study according to the GCP Guidelines. Trial data, including positive, negative and inconclusive results, will be presented at national and international scientific meetings and conferences. Papers will be submitted to peer-reviewed journals.Trial registrationClinicalTrials.gov identifier: NCT01794429; National Committee on Health Research Ethics project number: 36378; EudraCT nr: 2012-005404-17; The Danish Data Protection Agency project number: RHP-2012-027.

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Glucagon-like peptide-1 analogs against antipsychotic-induced weight gain: potential physiological benefits

Cited by 25 publications

References 70 publications

Glucometabolic Hormones and Cardiovascular Risk Markers in Antipsychotic-Treated Patients

Glucometabolic Hormones and Cardiovascular Risk Markers in Antipsychotic-Treated Patients

Sustained Weight Loss After Treatment With a Glucagon-Like Peptide-1 Receptor Agonist in an Obese Patient With Schizophrenia and Type 2 Diabetes

Treatment of antipsychotic-associated obesity with a GLP-1 receptor agonist—protocol for an investigator-initiated prospective, randomised, placebo-controlled, double-blinded intervention study: the TAO study protocol

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