The effect of glucagon-like peptide-1 (GLP-1) receptor agonists on substance use disorder (SUD)-related behavioural effects of drugs and alcohol: A systematic review

Glucagon-like-peptide-1 (GLP-1)-receptor agonists have been proposed as putative treatment for substance use disorders (SUD). The objective of this systematic review is to characterize the effects of GLP-1-receptor agonists on SUD-related behavioural effects of drugs, nicotine, and alcohol. The review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A search was performed in PubMed and EMBASE on June 16, 2018. The inclusion criteria were primary studies investigating the use of GLP-1-receptor agonists on behavioural endpoints related to SUD. Seventeen studies were included, investigating the effect of the GLP-1-receptor agonists exendin-4, fluoroexendin-4, liraglutide, AC3174 and GLP-1 (7-36) on SUD-related behavioural effects of ethanol, cocaine, amphetamine, and/or nicotine. All studies used rodents as subjects. Nine of the studies dealt with ethanol, six with cocaine, two with amphetamine, and two with nicotine. Most studies investigated acute treatment effects, finding a significant effect in all but one experiment. A few studies investigated more chronic effects on ethanol. All the studies reported sustained effects. Eleven studies tested more than one dose, finding a dose-related response in ten out of thirteen experiments. Six studies report a central effect through infra-cerebral administration or by using mice in which the central GLP-1-receptors had been inactivated. In conclusion, a solid body of evidence documents acute effects of GLP-1-receptor agonist treatment on behavioural effects of alcohol, nicotine, amphetamine and cocaine. Documentation of effect of more chronic GLP-1-receptor stimulation on these behaviours is limited.