Brain recordings show tirzepatide briefly silences food noise in one woman with obesity, but the effect appears temporary.

A rare brain study using implanted electrodes found that tirzepatide, sold as Mounjaro and Zepbound, quiets brain signals linked to constant thoughts about food, but the effect appears temporary.

Researchers monitored brain activity in a 60-year-old woman with severe obesity who had electrodes surgically implanted as part of a clinical trial for treatment-resistant obesity.

The patient, identified as “Participant 3”, struggled with obsessive thoughts about food, leading to ordering takeaway or continual snacking even when she wanted to resist.

She reported eating large amounts until uncomfortably full, particularly pre-packaged cupcakes, fast-food roast beef sandwiches and French fries.

The woman had tried to manage her obesity through bariatric surgery, medication, behavioural therapy and weight-loss drugs.

She had also been prescribed dulaglutide, a GLP-1 inhibitor (a class of drugs that mimic hormones regulating blood sugar and appetite), which did not affect her weight or food preoccupation.

When prescribed tirzepatide for her type 2 diabetes before the brain surgery, the team gained a rare opportunity to observe how the drug alters brain signals tied to eating behaviour in real time.

Casey H. Halpern, is professor of neurosurgery and head of the division of stereotactic and functional neurosurgery at the Perelman School of Medicine at the University of Pennsylvania.

The researcher said: “Brain surgery to implant the electrodes is invasive, and thus it is extremely rare to study human brain activity in this way.

“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.”

The electrodes were implanted in the nucleus accumbens (NAc), a region that helps regulate motivation and guides decisions around pleasure-seeking and impulse control.

Prior work shows that in people with obesity and binge eating disorder, signalling in this circuit is dysregulated.

After she reached her full dose of tirzepatide following surgery, the participant reported no food preoccupation and her NAc activity was quiet.

After five months, NAc activity returned to levels consistent with obesity, along with reports of severe food preoccupation, suggesting the drug’s effect was temporary.

In contrast, trial participants not taking tirzepatide showed the expected elevated NAc activity and frequent episodes of food preoccupation throughout monitoring.

Up to 60 per cent of people with obesity report experiencing “food noise”, meaning persistent thoughts about food that drive distress and dysregulated eating behaviours.

Binge eating disorder affects at least three million people in the US and is considered the country’s most common eating disorder.

“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,” Halpern said.

GIP inhibitors work alongside GLP-1 to regulate blood sugar and appetite.

Tirzepatide targets both GLP-1 and GIP receptors and was developed to manage type 2 diabetes.

“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,” said study investigator Kelly Allison, professor of psychiatry and director of the Center for Weight and Eating Disorders.

“This research shows us that they might be useful to manage food preoccupation and binge eating, but not in their current form.”

The clinical trial involves implanting intracranial electroencephalography (iEEG) electrodes, a technique that records electrical activity in the brain, similar to devices used to treat drug-resistant epilepsy and Parkinson’s disease.

The electrodes record NAc activity as participants encounter foods that typically trigger binge eating episodes.

Halpern’s previous research identified distinctive electrical activity in the NAc that arises just before food preoccupation and the urge to binge, but not when someone is simply hungry before a normal meal.

A pilot trial showed that delivering high-frequency stimulation to the NAc when craving-linked signals occurred could prevent binge eating behaviours.

“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,” said co-first author Wonkyung Choi, a PhD 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.”