Glucagon‐like peptide‐1 receptor agonists for antipsychotic‐associated cardio‐metabolic risk factors: A systematic review and individual participant data meta‐analysis

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. Materials and methods 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 Three 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 significantly lower with GLP‐1RA. Sex, age, psychosis severity, nausea, any ADR, and GLP‐1RA agent did not significantly impact outcomes. 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). 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.