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

OBJECTIVE:

Patients with schizophrenia have higher cardio-metabolic risk, partially from antipsychotic-induced weight-gain. Glucagon-like-peptide-1 receptor-agonists (GLP-1RAs) may reduce antipsychotic-associated weight-gain, however, safety and efficacy in schizophrenia has not been systematically reviewed.

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. Primary outcome was difference in body weight between GLP-1RA and control; secondary outcomes included cardio-metabolic parameters and adverse drug reactions (ADRs). Multiple linear regression was conducted including sex, age, psychosis severity, metabolic parameter, 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±11.1years, weight=105.8±20.8kg). After 16.2±4.0 weeks of treatment, weight loss was 3.71 kg (95% CI=2.44-4.99 kg) greater for GLP-1RA vs. control (p<0.001), number-needed-to-treat ≥5% weight-loss=3.8 (95%CI=2.6-7.2). Waist, BMI, 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. Weight loss with GLP-1RAs was greater for clozapine-/olanzapine-treated patients (n=141) than other antipsychotics (n=27) (4.70kg, 95%CI=3.13-6.27 vs 1.5kg 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 weight-gain, particularly clozapine-/olanzapine-treated patients. With few included patients, further studies are required before making routine use recommendations for GLP-1RAs. This article is protected by copyright. All rights reserved.