The therapeutic potential of GLP-1 analogues for stress-related eating and role of GLP-1 in stress, emotion and mood: a review

• Published in: Progress in neuro-psychopharmacology & biological psychiatry 2021-08, Vol.110, p.110303-110303, Article 110303
• Main Authors: Guerrero-Hreins, Eva, Goldstone, Anthony P., Brown, Robyn M., Sumithran, Priya
• Format: Article
• Language: English
• Subjects: Addiction; Affect - drug effects; Affect - physiology; Animals; Anti-Obesity Agents - administration & dosage; Brain-Gut Axis - drug effects; Brain-Gut Axis - physiology; Clinical Trials, Phase III as Topic - methods; Emotion; Emotions - drug effects; Emotions - physiology; Exenatide - administration & dosage; GLP-1; Glucagon-Like Peptide 1 - administration & dosage; Glucagon-Like Peptide 1 - analogs & derivatives; Humans; Hyperphagia - drug therapy; Hyperphagia - metabolism; Hyperphagia - psychology; Mood; Obesity; Obesity - drug therapy; Obesity - metabolism; Obesity - psychology; Stress; Stress, Psychological - drug therapy; Stress, Psychological - metabolism; Stress, Psychological - psychology
• ISSN: 0278-5846; 1878-4216
• DOI: 10.1016/j.pnpbp.2021.110303

Stress and low mood are powerful triggers for compulsive overeating, a maladaptive form of eating leading to negative physical and mental health consequences. Stress-vulnerable individuals, such as people with obesity, are particularly prone to overconsumption of high energy foods and may use it as a coping mechanism for general life stressors. Recent advances in the treatment of obesity and related co-morbidities have focused on the therapeutic potential of anorexigenic gut hormones, such as glucagon-like peptide 1 (GLP-1), which acts both peripherally and centrally to reduce energy intake. Besides its appetite suppressing effect, GLP-1 acts on areas of the brain involved in stress response and emotion regulation. However, the role of GLP-1 in emotion and stress regulation, and whether it is a viable treatment for stress-induced compulsive overeating, has yet to be established. A thorough review of the pre-clinical literature measuring markers of stress, anxiety and mood after GLP-1 exposure points to potential divergent effects based on temporality. Specifically, acute GLP-1 injection consistently stimulates the physiological stress response in rodents whereas long-term exposure indicates anxiolytic and anti-depressive benefits. However, the limited clinical evidence is not as clear cut. While prolonged GLP-1 analogue treatment in people with type 2 diabetes improved measures of mood and general psychological wellbeing, the mechanisms underlying this may be confounded by associated weight loss and improved blood glucose control. There is a paucity of longitudinal clinical literature on mechanistic pathways by which stress influences eating behavior and how centrally-acting gut hormones such as GLP-1, can modify these. (250) •Compulsive overeating is commonly triggered by stress and negative mood.•GLP-1R are found in stress, emotion and reward regulatory areas in the brain.•GLP-1R agonists induce acute anxiogenic yet chronic anxiolytic states in rodents.•Long-term GLP-1R agonist clinical trials measuring stress, mood and eating are needed.•Promising evidence for GLP-1R agonists for depression and drug addiction treatment.