Brain recordings suggest tirzepatide's effect on food noise may fade after about five months

A case study published Nov. 17, 2025, in Nature Medicine reports a first-in-human recording of electrical activity inside the brain of a person taking tirzepatide, sold as Mounjaro and Zepbound. The recording showed the drug quieted food-related brain signals and food preoccupation, then both returned about five months later ^[1][2][3].

The recordings came from a 60-year-old woman described in the report as "Participant 3." She had severe, treatment-resistant obesity, type 2 diabetes and loss-of-control eating, and she reported obsessive thoughts about food that led to ordering takeout or constant snacking even when she wanted to resist ^[2][3]. She had already tried dulaglutide, a GLP-1 receptor agonist, which the report says did not affect her weight or her food preoccupation ^[2][3]. Her doctor prescribed tirzepatide, a GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, to manage her diabetes ahead of surgery, and the dose was raised slowly to the maximum before and after electrodes were implanted in her brain ^[2][3].

The electrodes were part of an ongoing early feasibility trial (NCT03868670) that enrolls people with treatment-refractory obesity and loss-of-control eating; four participants have been enrolled ^[1][2][3]. Because Participant 3 was already taking tirzepatide when she joined and had not yet received any electrical stimulation, the team could observe the drug's effect on brain signals on its own ^[2][3].

Once she reached the full dose, she reported no food preoccupation, and activity in the nucleus accumbens linked to those episodes was silent ^[2][3]. About five months later, that activity was detected again — in a pattern the researchers say is expected in someone with obesity — along with reports of severe food preoccupation ^[2][3]. The paper reports increased delta–theta frequency (7 Hz or below) power in the nucleus accumbens before episodes of severe food preoccupation, and the authors propose that tirzepatide's effect on food preoccupation may involve modulating abnormal activity in this hub of the mesolimbic circuit ^[1]. The trial's other participants, who were not taking tirzepatide, showed the expected elevated nucleus accumbens activity and frequent food preoccupation episodes ^[2][3].

"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," said senior author Casey H. Halpern, MD, a professor of neurosurgery at the University of Pennsylvania's Perelman School of Medicine ^[2][3]. Study investigator Kelly Allison, PhD, said the research shows the drugs "might be useful to manage food preoccupation and binge eating, but not in their current form" ^[2][3]. Co-first author Wonkyung Choi noted the report covers only one person taking tirzepatide ^[2][3].

The paper cites earlier data pointing to a tolerance effect for food preoccupation with incretin-based therapies ^[1]. Whether the pattern seen in this patient is common among people taking tirzepatide has not been established, and what caused the effect to fade in her case has not been reported. It is also not yet known whether the return of these brain signals affected her weight or blood sugar control ^[2][3].

Why it matters for patients

Up to 60 percent of people with obesity report food noise — constant thoughts about food that cause distress and can lead to loss-of-control eating and binge eating — and binge eating disorder is considered the most common eating disorder in the United States, affecting at least more than 3 million people ^[2][3]. An association between binge eating and suicide risk has also been established in patients with obesity and related eating disorders, according to the study team ^[2][3].

For people taking tirzepatide, this is a single case, not a general finding. It does raise the possibility that the quieting of food noise some patients describe may not last for everyone. The medications are not FDA-approved to treat food preoccupation or the impulsivity that can come with it, and the researchers say their impact on human brain activity has only begun to be studied ^[2][3].

What happens next

The findings were published Nov. 17, 2025, in Nature Medicine ^[2][3]. The trial that produced them is an ongoing early feasibility study of brain-responsive stimulation for loss-of-control eating, and Participant 3's tirzepatide observations came before any stimulation was delivered ^[1][2][3]. No timeline for further results has been disclosed. Halpern said the study "will guide us as we explore new indications" ^[2][3].