Aims: To evaluate if glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce antipsychotic-associated body weight gain in patients with schizophrenia, when compared to controls.
Method: We systematically searched PubMed/Embase/PsycINFO/Cochrane using the search terms
(antipsychotic and GLP-1RA). Individual participant data from studies randomizing patients to GLP-1RA or control were meta-analysed. The primary outcome was difference in body weight between GLP-1RA and control; secondary outcomes included cardio-metabolic variables and adverse drug reactions (ADRs). Multiple linear regression was conducted including sex, age, psychosis severity, metabolic variable, ADRs, and GLP-1RA agent.Results: 3 studies (exenatide once-weekly = 2; liraglutide once-daily = 1) provided participant-level data (n = 164, age = 40.0 ± 11.1 years, body weight = 105.8 ± 20.8 kg). After 16.2 ± 4.0 weeks of treatment, body weight loss was 3.71 kg (95% CI = 2.44-4.99 kg) greater for GLP-1RA versus control (p < 0.001), number-needed-to-treat ≥5% body weight loss = 3.8 (95% CI = 2.6-7.2). Waist circumference, body mass index, HbA1c, fasting glucose and visceral adiposity were each statistically-significantly lower with GLP-1RA.
Body weight loss with GLP-1RAs was greater for clozapine/olanzapine-treated patients (n = 141) than other antipsychotics (n = 27) (4.70 kg, 95% CI = 3.13-6.27 vs. 1.5 kg, 95% CI = −1.47-4.47) (p < 0.001).
Sex, age, psychosis severity, nausea, any ADR, and GLP-1RA agent did not statistically-significantly impact outcomes.
Nausea was more common with GLP-1RAs than control (53.6% vs. 27.5%, p = 0.002, number-needed-to-harm = 3.8).
Conclusion: GLP-1RAs are effective and tolerable for antipsychotic-associated body weight gain, particularly clozapine/olanzapine-treated patients. With few included patients, further studies are required before making routine use recommendations for GLP-1RAs.