A systematic review conducted by the scientists at Staten Island University Hospital, US, describes the utility of glucagon-like peptide-1 receptor agonists in reducing binge eating behaviors in individuals with binge eating disorder and bulimia nervosa.

The research is published in the Journal of Clinical and Translational Endocrinology.

Study: GLP-1 receptor agonists: A novel pharmacotherapy for binge eating (Binge eating disorder and bulimia nervosa)? A systematic review. Image Credit: Creativa Images / ShutterstockStudy: GLP-1 receptor agonists: A novel pharmacotherapy for binge eating (Binge eating disorder and bulimia nervosa)? A systematic review. Image Credit: Creativa Images / Shutterstock

Background

Consumption of an abnormally large amount of food within a short period is the primary symptom of both binge eating disorder and bulimia nervosa. The estimated lifetime prevalence of binge eating disorder and bulimia nervosa worldwide is 1.9% and 1%, respectively.

Psychological and pharmacological interventions are considered the first line of treatment for eating disorders. While psychological interventions, such as cognitive behavioral therapy, primarily deal with emotional and behavioral aspects of the disorder, pharmacological interventions mainly involve selective serotonin reuptake inhibitors to manage the symptoms.

Pharmacological medicines (topiramate and lisdexamfetamine) that are currently approved for these eating disorders are associated with adverse side effects, such as headache, paresthesia, sedation, and increased heart rate and blood pressure. This highlights the need for identifying novel pharmacological interventions.

Glucagon-like peptide-1 (GLP-1) is a hormone and neuropeptide produced in the intestine and brain. This hormone inhibits appetite, reduces food intake, reduces body weight, and stimulates glucose-dependent insulin secretion by activating GLP-1 receptors. Activation of this receptor is known to regulate normal feeding behavior and reward-driven feelings.

GLP-1 receptor agonists (GLP-1RAs) are currently used for treating type-2 diabetes and obesity because of their effects on appetite, food intake, and body weight loss. These effects make GLP-1RAs a suitable choice for treating binge eating disorder and bulimia nervosa.

In this systematic review, authors systematically analyzed existing literature on using GLP-1RAs in managing binge eating behaviors.

The authors screened various scientific databases to identify studies that investigated the effectiveness of GLP-1RAs in eating disorders, including binge eating disorder and bulimia nervosa.

Prevalence of eating disorder

The systematic analysis of the selected studies indicates that about 8% of respondents have eating disorders and 3% experience recurrent episodes. Episodes mostly occur in the morning and early evening, and 40% of respondents experience less than four hours of fasting beforehand.

Women (10%) are significantly more likely to experience binge eating than men (6%). Moreover, the prevalence of binge eating is higher among younger respondents aged 20 – 29 years, which decreases with increasing age.

Existing evidence indicates that eating disorders can increase the risk of diabetes, obesity, hypertension, hypertriglyceridemia, headache, back pain, and other chronic metabolic diseases.

GLP-1RA a promising intervention

Existing literature shows that GLP-1RAs work through both central and peripheral mechanisms to regulate gut signals, brain appetite networks, and food preferences and cravings.

Upon detection of dietary nutrients in the gut, GLP-1 is released from the intestinal L cells and binds to its receptor. The receptor binding subsequently triggers cAMP levels, leading to an induction in insulin secretion. Furthermore, GLP-1 reduces the rate of gastric emptying and glucagon release.

Animal studies have shown that GLP-1RAs control appetite and binge eating behavior through serotonin pathways. Mechanisms deciphered in these studies indicate that the interaction between serotonin and GLP-1 in the hindbrain increases proopiomelanocortin/cocaine- and amphetamine-regulated transcript (POMC/CART) neuron activity, leading to induction of satiety signals and suppression of neuropeptide Y/agouti-related peptide (NPY/AgRP) neuron activity, which in turn suppresses hunger.    

Activation of POMC neurons leads to the release of alpha-melanocyte-stimulating hormone (α-MSH), which subsequently binds to the melanocortin 4 receptor in the paraventricular nucleus of the hypothalamus and triggers appetite-inhibiting signaling cascade.

These brain chemicals indirectly influence the CA1 region of the ventral hippocampus, leading to the modulation of hunger and, satiety and emotional responses to foods.

Overall, these findings indicate that GLP-1 agonism is part of the final effects of selective serotonin reuptake inhibitors and that GLP-1RA can be a promising treatment for binge eating disorder.

Regarding tolerability, evidence indicates that GLP-1RAs are safe for non-diabetic obese patients. However, the treatment may cause mild to moderate gastrointestinal problems, such as nausea, vomiting, and diarrhea.  

Pharmacokinetics and therapeutic potentials of GLP-1RAs

Liraglutide (Victoza) is a fatty acid-attached GLP-1 analog (GLP-1RA) that is administered through once-daily injection. It can cross the blood-brain barrier and positively influence nerve growth and protection. A randomized controlled trial conducted on obese people has shown that a 12-week treatment with Liraglutide can reduce binge eating behavior and cause weigh loss in patients with binge eating disorder.

Liraglutide has also been found to reduce food obsessions, overeating, aggression, and other repetitive behaviors in a patient with autism spectrum disorder, intellectual disability, and obsessive eating disorder.   

Semaglutide (Ozempic) is a long-acting GLP-1 analog with higher receptor binding ability compared to liraglutide. Treatment with Semaglutide (weekly dosing) has been found to reduce overeating behavior, food cravings, and preference for high-fat, high-calorie foods.    

Dulaglutide (Trulicity) is another GLP-1 analog administered weekly. Treatment with Dulaglutide has been found to reduce binge eating frequency, body weight, body mass index, body fat percentage, and glycated hemoglobin in diabetic patients with binge eating disorder.



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