For the first time, deep-brain recordings from a patient with obesity have revealed how the drug tirzepatide, sold as Mounjaro and Zepbound, temporarily quiets the brain’s “food noise.” While the medication sharply reduced craving-related signals for several months, the compulsive thoughts eventually returned, highlighting the need for more durable treatments for binge eating and impulsivity. The findings, led by researchers at the University of Pennsylvania Perelman School of Medicine, were published in Nature Medicine.
The study focused on a 60-year-old woman with severe, treatment-resistant obesity and persistent “food noise”intrusive thoughts about food that often led to binge eating. As part of a clinical trial, she underwent surgery to implant electrodes in her brain’s nucleus accumbens, a reward region linked to cravings.
Before the electrodes were activated, she was prescribed tirzepatide for Type 2 diabetes. Over five months, she reported no food preoccupation, and her brain recordings showed markedly reduced activity in craving circuits. After that period, however, both the “food noise” and related brain signals returned, suggesting the drug’s effects on compulsive eating were temporary.
Senior author Dr. Casey H. Halpern explained that tirzepatidea dual GLP-1 and GIP receptor agonistwas originally developed for diabetes and weight loss. While many patients report reduced food cravings on such drugs, this study offers the first direct evidence of how they alter brain activity in real time.
“This research shows us that [GLP-1 and GIP inhibitors] might be useful to manage food preoccupation and binge eating, but not in their current form,” said study investigator Dr. Kelly Allison, Director of the Center for Weight and Eating Disorders.
Co-first author Wonkyung Choi added, “These insights should inspire further research into developing a treatment better tailored to the impulsivity traits of obesity and related eating disorders that is safe and long-lasting.”
The case study underscores that while drugs like Mounjaro can temporarily calm craving circuits, they may not provide a lasting solution for conditions like binge eating disorder. The authors emphasize the need for more targeted, sustained therapies and further research into how these medications interact with the brain. The work was supported by the National Institutes of Health.