In a pioneering work published in 2016 in the journal, Cogent Biology, Dr. Stefan Trapp, along with his colleague, Dr. Marie K. Holt, teases out the relationship between the GLP-1 system and stress. Their extensive review, available in full online, made these points:

• The GLP-1 system plays a role in regulating food intake.
• However, the GLP-1 system may be responsible for much wider homeostatic control.
• Overactivation of brain GLP-1 receptors enhances the secretion of stress hormones.
• The anorexic effects of GLP-1 may be secondary responses to stress.

Dr. Trapp is head of the University College of London’s Center for Cardiovascular and Metabolic Neuroscience. His review is quite a detailed excursion into neuroscience, which I barely understand. But the conclusion speaks volumes about the relationship between GLP-1, appetite, and stress:

The evidence discussed here suggests that central GLP-1 does not simply regulate food intake in response to changes in energy demand, but that the PPG [preproglucagon] neurons are activated by stress and that central GLP-1 modulates acute stress, homeostatic or psychogenic, by increasing corticosterone, mobilising glucose and increasing heart rate, allowing the organism to cope with potential threats.

You would think this finding, that GLP-1 receptor agonist drugs might be moderating appetite by managing the stress response, would warrant further investigation. Indeed, it has. We’ll look at three recent studies that expand on Dr. Trapp’s work.

In 2020, a team of researchers in Spain published a review in the scientific journal, Nutrients, that concluded, “Alterations in GLP-1 signaling associated with obesity or chronic stress induce the dysregulation of eating behavior.” They further find that the GLP-1 system is a “neuromodulator coordinating food intake in response to a physiological and stress-related stimulus.”

The researchers follow this interesting chain of events:

• Chronic stress and major acute stress are associated with weight gain.
• Stress results in a shift to more pleasurable, palatable foods.
• The dopamine released over time hijacks the brain’s reward system.

“In this respect,” the researchers write, “stress becomes a critical risk factor affecting both the development of addictive disorders and relapse to addictive behaviors.” And it’s not just eating behaviors. It’s all addictive behaviors that are responses to stress. In other words, GLP-1 drugs blunt the stress that motivates most behavioral disorders.

The researchers explain the connection: Stress elicits “activation of the autonomic sympathetic nervous system (‘fight or flight’ response), that facilitates the secretion of noradrenaline and adrenaline by the adrenal medulla.” This results in an increase in heart rate, blood glucose levels, and other signs of stress. “In the context, GLP-1 emerges as a critical neuromodulator that mediates the response to stressors,” they conclude.

In 2021, a group of Australian scientists looked at the role of the GLP-1 system in moderating stress, emotion and mood. The focus of their review in the journal Progress in Neuro-Psychopharmacology and Biological Psychiatry is on the GLP-1 system and stress-related eating, but it quickly becomes much broader than just eating addiction:

Besides its appetite suppressing effect, GLP-1 acts on areas of the brain involved in stress response and emotion regulation.

Their discovery that “prolonged GLP-1 analogue treatment in people with type 2 diabetes improved measures of mood and general psychological wellbeing,” is a tantalizing result that begs for more detail. Do people feel less anxiety because of the GLP-1 drugs, or is it due to weight loss and improved appetite control?

That brings us to theJournal of the Endocrine Society, which published the findings of a pair of Chinese researchers into how GLP-1 drugs impact “oxidative stress.” They examined the results of 26 randomized controlled trials of GLP-1 drugs involving 1976 patients with type 2 diabetes.

Oxidative stress was measured by serum malondialdehyde (MDA), a reliable biomarker for measuring stress. “A positive correlation was found between serum MDA and body mass index in patients with [type 2 diabetes] treated with GLP-1 RAs,” the researchers write, concluding:

This meta-analysis provides clear evidence of clinically relevant significant antioxidative stress effects of GLP-1 RAs.

While there appears to be a unanimous conclusion that GLP-1 drugs are impacting not just appetite but stress, there seems to be little awareness of where that stress goes. Are there benefits to stress, such as survival, that might be curtailed by the use of GLP-1 drugs? The fact that the compulsive behavior usually returns soon after GLP-1 drugs are taken away indicates the stress hasn’t gone anywhere. We’ll look for the missing stress in a future column at AddictionNews.

Written by Steve O’Keefe. First published March 10, 2026.

Sources:

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

“Glucagon-Like Peptide-1 (GLP-1) in the Integration of Neural and Endocrine Responses to Stress,” Nutrients, October 27, 2020.

“The therapeutic potential of GLP-1 analogues for stress-related eating and role of GLP-1 in stress, emotion and mood: a review,” Progress in Neuro-Psychopharmacology and Biological Psychiatry, August 30, 2021.

“Effect of GLP-1 RA and SGLT2I on Biomarkers of Oxidative Stress in T2DM: A Systematic Review and Meta-analysis,” Journal of the Endocrine Society, August 2025.

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