It’s very interesting that GLP-1 drugs were first approved by the Food and Drug Administration (FDA) in 2005 for the treatment of type 2 diabetes when they easily could have been approved first for the treatment of many other problems, including obesity, alcoholism, depression, heart disease, and even behavioral disorders.

The first GLP-1 drug, exenatide, was approved on the basis of managing blood glucose levels. Users felt full more quickly. In fact, they kind of feel full all the time, which leads to a significant amount of intestinal discomfort. Somehow, this intestinal discomfort reduces people’s interest in previously compelling activities such as binge eating, binge drinking, binge shopping, and binge gambling.

Maybe there is some connection between GLP-1 drugs and bingeing? It turns out there is, but the connection is in the brain as well as the gut. In 2020, researchers from CINBIO, the Nanomaterials and Biomedicine Research Center at the University of Vigo in Spain, published a review on the connection between GLP-1 receptors and stress management. Their work reveals a close relationship between GLP-1 receptors and stress that could be far more important than the connection with glucose levels.

Let’s follow the trail of stress in the brain. First, preproglucagon neurons project into the hypothalamus and other brain areas where they control autonomic functioning, including feeding, the motivation to feed, and the stress response. In particular, the researchers found that:

[T]he essential central actions of GLP-1 as neuromodulator coordinating food intake in response to a physiological and stress-related stimulus to maintain homeostasis.

The researchers found that disruptions of GLP-1 signaling are associated with dysregulated eating behavior that is associated with obesity and chronic stress. In one beautiful paragraph, the researchers explain that the stress response is the source of both eating disorders and behavioral disorders:

Different aversive physiological stimuli such as hypoglycemia, hypotension, hypoxia, hypovolemia, hypothermia, infection, and also psychological stressors, elicit a response that is characterized by the activation of the autonomic sympathetic nervous system (“fight or flight” response), that facilitates the secretion of noradrenaline and adrenaline by the adrenal medulla. This response elicits rapid modifications in physiological states through neural innervation of end organs (increasing heart rate and blood glucose among others), and it is counter regulated and compensated by the parasympathetic (“rest and digest”) nervous system. Moreover, the stressors also activate the HPA [hypothalamic-pituitary-adrenal] axis and stimulate the synthesis and secretion of glucocorticoids from the adrenal cortex. In this context, GLP-1 emerges as a critical neuromodulator that mediates the response to stressors.

The researchers write that “dysfunctional stress responses” are the source of substance use disorders, psychiatric disorders, and neurodegenerative diseases. GLP-1 receptor agonist drugs “mediate anxiety responses” in the central nervous system. The researchers say that not only do GLP-1 drugs “modulate the acute stress response,” they also regulate HPA responsiveness to chronic stress.

In another fascinating conclusion teased out of the data by the Spanish researchers, they discovered that GLP-1 drugs are particularly effective at reducing binge eating “in response to stress.” “There is an overlap between the stress and feeding systems,” researchers observe, describing the process:

• The amount and type of food eaten are influenced by stress.
• Many types of stress are associated with reduced food intake.
• However, 80% of people increase caloric intake under stressful circumstances.
• More of those calories come from highly-palatable foods during stressful situations.

The researchers conclude that “chronically stressed individuals are more susceptible to weight gain, obesity, type II diabetes, [and] cardiovascular diseases.” Under this theory of the way GLP-1 drugs work, they should reduce stress-related binge eating, but also increase eating by animals that reduce consumption when stressed. In other words, GLP-1 drugs should work both ways, reducing the stress response, whether that is more eating or less eating.

Now we’re getting somewhere. GLP-1 drugs appear not to reduce the appetite, but to reduce eating to relieve stress. It just so happens that a common stress response is binge eating of highly-palatible foods, and GLP-1 drugs appear to work by reducing stress-related eating. They also appear to reduce the stress-related symptoms of withdrawal from drugs of addictions. They also appear to reduce stress-related substance abuse. And they appear to reduce stress-related compulsions of all kinds, such as gambling addiction, shopping addiction, pornography addiction, or any activity people turn to compulsively to relieve stress.

In the interaction between the sympathetic and parasympathetic nervous systems, there is a constant attempt to displace stress to maintain homeostasis. Faced with chronic stress, humans will attach to almost any behavior as a relief valve, often becoming dependent upon self-harming behaviors in order to achieve a sense of peace. GLP-1 drugs offer an interesting possibility of medicated stress management that so far has shown a multitude of positive benefits and few signs of adverse effects.

Written by Steve O’Keefe. First published March 31, 2026.

Sources:

“Glucagon-Like Peptide-1 (GLP-1) in the Integration of Neural and Endocrine Responses to Stress,” Nutrients, October 28, 2020.

“The physiological role of the brain GLP-1 system in stress,” Cogent Biology, September 14, 2016.

“Role of central glucagon-like peptide-1 in stress regulation,” Physiology & Behavior, October 2, 2013.

Image Copyright: iakovenko.