Effect of GLP ‐1 receptor agonist treatment on body weight in obese antipsychotic‐treated patients with schizophrenia: a randomized, placebo‐controlled trial
Open accessAbstract
AIMS: receptor antagonists and are the standard of medical care in schizophrenia, but the drugs are associated with severe metabolic side effects such as obesity and diabetes. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are registered for treatment of both obesity and type 2 diabetes. We investigated metabolic effects of the GLP-1RA, exenatide once-weekly, in non-diabetic, antipsychotic-treated, obese patients with schizophrenia. MATERIAL AND METHODS: Antipsychotic-treated, obese, non-diabetic, schizophrenia spectrum patients were randomized to double-blinded adjunctive treatment with once-weekly subcutaneous exenatide (n = 23) or placebo (n = 22) injections for 3 months. The primary outcome was loss of body weight after treatment and repeated measures analysis of variance was used as statistical analysis. RESULTS: Between March 2013 and June 2015, 40 patients completed the trial. At baseline, mean body weight was 118.3 ± 16.0 kg in the exenatide group and 111.7 ± 18.0 kg in the placebo group, with no group differences ( P = .23). The exenatide and placebo groups experienced significant ( P = .004), however similar ( P = .98), weight losses of 2.24 ± 3.3 and 2.23 ± 4.4 kg, respectively, after 3 months of treatment. CONCLUSIONS: Treatment with exenatide once-weekly did not promote weight loss in obese, antipsychotic-treated patients with schizophrenia compared to placebo. Our results could suggest that the body weight-lowering effect of GLP-1RAs involves dopaminergic signaling, but blockade of other receptor systems may also play a role. Nevertheless, anti-obesity regimens effective in the general population may not be readily implemented in antipsychotic-treated patients with schizophrenia.
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Preliminary evidence supports the efficacy of GLP-1 receptor agonists in antipsychotic-associated weight gain.
“with preliminary evidence supporting efficacy in AAWG.”
From Semaglutide for the treatment of antipsychotic-associated weight gain in patients not responding to metformin – a case series (2023) · cites this paper as [49]
The Results (Primary outcome; page not available) report that exenatide and placebo produced similar weight loss after three months in obese, antipsychotic-treated patients with schizophrenia. This trial therefore does not provide the claimed preliminary evidence of efficacy for antipsychotic-associated weight gain. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredLiraglutide results were comparable and possibly superior to off-label metformin in mean weight (-5.29 kg vs -3.24 kg) and BMI (-1.69 kg/m2 vs -1.11 kg/m2) change.
“Particularly interesting was how the results were comparableand possibly superiorto off-label metformin in terms of mean weight (-5.29 kg (95% CI: -6.86 to -3.71) vs -3.24 kg (95% CI: -4.72 to -1.76)) and BMI (-1.69 kg/m 2 (95% CI: -2.99 to -0.40) vs -1.11 kg/m 2 (95% CI: -1.62 to 0.60) change [65].”
From A systematic review of licensed weight-loss medications in treating antipsychotic-induced weight gain and obesity in schizophrenia and psychosis. (2022) · cites this paper as [65]
The Methods and Results (pages unavailable) describe an exenatide-versus-placebo trial, not a liraglutide-versus-metformin comparison. Searches for liraglutide, metformin, and the quoted weight and BMI changes found no passage reporting that comparison or those figures. (LLM, conf=0.77)
Experimental — accuracy not yet measuredWe intentionally included a naturalistic trial population, which is reflected in the broad medication profiles.
“Moreover, we intentionally included a naturalistic trial population (18), which is reflected in the broad medication profiles (Supplementary Table 1).”
After 3 months of exenatide or placebo treatment patients lost 2.3 kg with no significant difference between groups.
“After 3 months of exenatide or placebo treatment patients lost 2.3 kg with no significant difference between groups (18, 20).”
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- Authors
- Ishøy, P. L., Knop, F. K., Broberg, B. V., Bak, N., Andersen, U. B., Jørgensen, N. R., Holst, J. J., Glenthøj, B. Y., & Ebdrup, B. H.
- Affiliations
- University of Copenhagen (DK)
- Center for Neuropsychiatric Schizophrenia Research, CNSR, and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, Mental Health Centre Glostrup University of Copenhagen Glostrup Denmark
- Corresponding author
- Ebdrup, Bjørn H.
- ORCID
- Venue
- Diabetes, Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2016-11-14
- Volume
- 19
- Issue
- 2
- Pages
- 162-171
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- PMC
- PMC5299524
- OpenAlex
- W4249844731
- Cited by
- 102
- References
- 40
- Citations by year
- 2026: 23 · 2025: 16 · 2024: 12 · 2023: 11 · 2022: 10 · 2021: 8 · 2020: 2 · 2019: 6 · 2018: 8 · 2017: 6
- FWCI
- 5.92
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes Obesity and Metabolism (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by-nc-nd)
- Funders
- University of Copenhagen (211-0649/11-3012)
- University of Copenhagen/Mental Health Services, Capital Region of Denmark (R25-A2701)
- Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS (R25-A2701)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- exenatide, GLP-1 receptor agonists, schizophrenia, obesity, antipsychotic-induced weight gain, weight loss, adjunctive therapy, dopaminergic signaling, metabolic side effects of antipsychotics
- MeSH terms
- Exenatide, Glucagon-Like Peptide-1 Receptor Agonists, Adult, Blood Glucose, Blood Pressure, Body Composition, Body Weight, Double-Blind Method, Female, Glycated Hemoglobin, Humans, Male, Middle Aged, Obesity, Peptides, Schizophrenia, Antipsychotic Agents, Venoms, Weight Loss, Absorptiometry, Photon, Treatment Outcome, Blood Pressure Monitoring, Ambulatory, Waist-Hip Ratio, Incretins, Waist Circumference, Young Adult
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