Casey Halpern, MD, factors to the nucleus accumbens on a mind CT of a affected person. Credit score: Penn Medication
A uncommon glimpse into the mind exercise of a affected person with weight problems and lack of management consuming on tirzepatide, marketed as Mounjaro and Zepbound, revealed that the remedy suppresses signaling within the mind’s “reward center” considered concerned in meals noise—however solely briefly.
Analysis means that the remedy, a glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, initially developed to handle kind 2 diabetes, could possibly deal with a variety of situations involving impulse management, like binge consuming dysfunction.
However though there could also be tantalizing clues for serving to sufferers with undesirable impulses, GLP-1 and GIP inhibitors is probably not optimally designed to deal with them sufficiently and wish additional analysis, in response to a case examine from the Perelman College of Medication on the College of Pennsylvania, printed in Nature Medication.
“This study offers major insights into how these drugs may work inside the brain and will guide us as we explore new indications,” stated senior writer Casey H. Halpern, MD, a professor of Neurosurgery, and head of the Division of Stereotactic and Purposeful Neurosurgery.
“Until we better understand their action on the brain, it’s far too soon to call GLP-1 and GIP inhibitors miracle drugs for more conditions beyond type 2 diabetes and obesity.”
A typical and debilitating situation
Lack of management of consuming is a particularly widespread downside, affecting hundreds of thousands of sufferers with weight problems in addition to varied consuming problems. Binge consuming dysfunction, or BED, is taken into account the most typical consuming dysfunction in the USA, affecting not less than greater than 3 million individuals. Individuals who binge eat have a way of dropping management over consuming and proceed to eat past the standard level of feeling full.
Consuming behaviors, together with bingeing, are regulated by mind circuits involving the hypothalamus and reward facilities, the nucleus accumbens (NAc). Particularly, the NAc regulates the motivation system within the mind and guides choices round pleasure-seeking and impulse management.
Earlier analysis has proven that in people with weight problems and BED, which are sometimes seen collectively, the signaling of the NAc and its circuitry inside the mind is dysregulated.
Even with out the prognosis of BED, as much as 60% of individuals with weight problems report experiencing “food noise” or enthusiastic about meals continuously, which ends up in misery and dysregulated consuming behaviors, like lack of management consuming and binge consuming.
“Food noise” can also be extraordinarily widespread to treating problems corresponding to bulimia nervosa and even anorexia nervosa. It’s notably essential to notice that an affiliation between the presence of binge consuming and suicide danger has been established in sufferers with weight problems and these consuming problems associated to shared impulsive traits and the related emotional dysregulation.
“Developing new ways to treat these patients is of the utmost importance,” stated Halpern. “While many individuals taking GLP-1 and GIP inhibitors report a reduction in food noise, these medications are not FDA-approved to treat food preoccupation and its related impulsivity. In fact, their impact on human brain activity has only begun to be studied.”
A brand new strategy to managing meals noise
A 60-year-old girl, recognized within the new report as “Participant 3,” was recognized with extreme, treatment-resistant weight problems, and struggled with meals noise. She usually had obsessive ideas about meals, resulting in ordering takeout or continuous snacking, even when she wished to withstand.
She reported consuming massive quantities of meals till she was uncomfortably full, preoccupied with each candy and salty meals, particularly pre-packaged cupcakes, fast-food roast beef sandwiches and French fries. Participant 3 additionally had kind 2 diabetes, and was prescribed dulaglutide, a GLP-1 inhibitor, which didn’t affect her weight or meals preoccupation.
Participant 3 tried unsuccessfully to handle her weight problems by way of all medical means attainable, from bariatric surgical procedure, to remedy, to behavioral remedy, and drugs for dysregulated consuming conduct and weight reduction. When these obtainable therapies failed, she enrolled in Halpern’s scientific trial that concerned mind surgical procedure with implanted electrodes to interface with the mind with the later aim to cease the cravings earlier than they begin.
The brain-binge connection
Halpern’s earlier analysis revealed distinctive electrical exercise within the NAc that arises simply earlier than somebody experiences meals preoccupation and the urge to binge, however not when they’re merely hungry earlier than regular meals.
A pilot trial beforehand led by Halpern and colleagues demonstrated that delivering high-frequency electrical stimulation to the NAc at any time when the craving-associated indicators occurred was capable of stop binge consuming behaviors.
On this present trial with 4 members enrolled, intracranial electroencephalography (iEEG) electrodes are implanted within the mind of an individual with weight problems affected by lack of management consuming, just like the gadgets used to check and deal with drug-resistant epilepsy and Parkinson’s illness. On this case, the machine information electrical exercise within the NAc as members encounter meals that sometimes set off binge consuming episodes.
After establishing every participant’s baseline, Halpern’s group packages the electrodes to ship high-frequency electrical stimulation to the NAc at any time when the craving-associated indicators occurred. Throughout this six-month interval, earlier members reported sharp reductions of their emotions of loss-of-control, and within the frequencies of their bingeing episodes.
A novel trial results in an much more distinctive analysis alternative
For the reason that first GLP-1 inhibitor didn’t work for her, Participant 3’s physician prescribed tirzepatide to assist handle her kind 2 diabetes earlier than her surgical procedure. As a result of diabetes could be a danger issue for infections after surgical procedure, her dose was slowly elevated to the utmost, main as much as, and following surgical procedure to implant the electrodes. This supplied researchers with a uncommon alternative to watch how tirzepatide impacts mind indicators associated to consuming conduct in actual time.
“Brain surgery to implant the electrodes is invasive, and thus it is extremely rare to study human brain activity in this way,” stated Halpern. “Research fuels more research. This participant was already taking tirzepatide when she enrolled in the trial, but before any stimulation was delivered, giving us a unique opportunity to make foundational observations about how the drug alters brain signals.”
Quick-term suppression, long-term questions
After the electrodes had been implanted and Participant 3 reached her full dose of tirzepatide, she reported no meals preoccupation and her associated NAc exercise was silent. Nevertheless, after a five-month interval, NAc exercise was detected, in keeping with what can be anticipated of somebody with weight problems, together with stories of extreme meals preoccupation—suggesting tirzepatide’s results on this affected person’s behavioral dysfunction had been short-term, and the “food noise” was breaking by way of.
In distinction, the members within the trial not taking tirzepatide confirmed the anticipated, elevated NAc exercise and frequent episodes of meals preoccupation, in keeping with earlier findings from the Halpern Lab. The placing quiet in Participant 3’s NAc signaling and meals preoccupation means that the tirzepatide was answerable for the short-term quieting of meals noise.
“GLP-1 and GIP inhibitors are amazing medications at doing what they were developed for—managing blood sugar in people with type 2 diabetes and weight loss in obesity,” examine investigator Kelly Allison, Ph.D., a professor of Psychiatry and Director of the Middle for Weight and Consuming Problems. “This research shows us that they might be useful to manage food preoccupation and binge eating, but not in their current form.”
“Although this study only featured the data from one person taking tirzepatide, it provides compelling data about how GLP-1 and GIP inhibitors alter electrical signals in the brain,” stated co-first writer Wonkyung Choi, a Ph.D. candidate in Halpern’s lab.
“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.”
Extra data:
Casey Halpern, Mind exercise related to breakthrough meals preoccupation in a person on tirzepatide, Nature Medication (2025). DOI: 10.1038/s41591-025-04035-5. www.nature.com/articles/s41591-025-04035-5
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Tirzepatide might solely briefly suppress mind ‘meals noise’ exercise (2025, November 17)
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