Effects of glucagon-like peptide-1 (GLP-1) mono-agonists on reward processing in animal models: a systematic review

Glucagon-like peptide-1 (GLP-1), indicated in the treatment of type 2 diabetes mellitus, influences reward processing, integral to disparate mental disorders. Emerging evidence suggests that GLP-1 receptor mono-agonists (GLP-1RAs) are potential treatment strategies for select mental disorders. Herein, we systematically review preclinical research documenting how GLP-1 and GLP-1RAs may impact reward function.

Relevant studies were identified through Web of Science, OVID (MedLINE, Embase, PsycInfo), and PubMed from database inception to June 28, 2026. Preclinical research investigating the association between GLP-1 and select GLP-1RAs and reward function was included. Reward functions assessed were food-, drug-, and sexual-related reward.

A total of 66 studies met inclusion and were synthesised herein. Taken together, results indicate that GLP-1 and GLP-1RAs affect measures of food-related, drug-associated, and sexual behaviours. GLP-1 administration was associated with a reduction in food intake and gross locomotor activity with respect to approaching and engaging in reward-seeking behaviours. When locally administered in selected brain regions of evaluated animal models, exenatide was associated with reduced substance use, food seeking, and sexual behaviours (p < 0.05). Similarly, liraglutide was observed to attenuate substance and food-related rewards (p < 0.05). In addition, semaglutide was demonstrated to reduce substance and sucrose intake, while dulaglutide is reported to reduce substance intake (p < 0.001).

Extant preclinical findings demonstrate a trend toward reductions in reward-associated behaviours following GLP-1RA administration. Our findings can also provide rationale and impetus for evaluating GLP-1RAs in the treatment of psychiatric disorders characterised by disturbance in hedonic function and behaviours.