Small study links tirzepatide to a temporary quieting of binge-eating brain signals

Researchers who recorded electrical activity inside the brain of a woman with severe loss-of-control eating reported that her food-craving signals went quiet while she was taking tirzepatide, and then returned about five months later. The report, published Nov. 17 in Nature Medicine, describes one person, and the researchers say the findings cannot be generalized to others ^[1][2]. Tirzepatide is sold as Mounjaro for type 2 diabetes and Zepbound for weight loss ^[1].

The report is the first direct measurement of brain activity in a person receiving tirzepatide ^[1].

The study followed four patients taking part in the first human trial of deep-brain stimulation for loss-of-control eating disorders such as binge-eating and bulimia. The plan was to monitor activity in the nucleus accumbens, a hub of the brain's reward circuitry, and to use a surgically implanted device to send electrical impulses aimed at blocking signals that ramp up before binge-eating episodes ^[1].

One participant had been prescribed tirzepatide by her own doctor before her electrodes were implanted, to treat type 2 diabetes and obesity. During the first few months of monitoring, she reported no food preoccupation, and her nucleus accumbens food-craving signals were silent. The other participants, who were not taking tirzepatide, showed the typical elevated activity in that region and frequent episodes of food preoccupation ^[1].

"Activity in her nucleus accumbens was so quiet that it almost made us think our system wasn't working," said study leader Dr. Casey Halpern of the Perelman School of Medicine at the University of Pennsylvania ^[1].

Five months later, the picture changed. Researchers detected nucleus accumbens activity consistent with binge-eating, and the patient reported episodes of severe food preoccupation ^[1]. The Nature Medicine paper calls this "breakthrough food preoccupation" and reports that the severe episodes were preceded by increased delta-theta frequency power at 7 Hz or below in the nucleus accumbens ^[2].

Halpern surmised that the effect on out-of-control eating was only temporary because tirzepatide was designed and optimized for diabetes and weight loss, not for binge-eating disorders. Current weight-loss drugs mimic hormones made in the small intestine and pancreas and were not designed to act on the brain's reward mechanisms, he said. A lasting effect on severe food preoccupation would require GLP-1 drugs to be redesigned to affect the nucleus accumbens and optimized for mental health, he said ^[1].

Receptors for the hormones these drugs mimic, GLP-1 and GIP, are found in central nervous system regions including the hypothalamus and the nucleus accumbens, according to the paper, which notes that food preoccupation affects up to 60% of patients with obesity and related eating disorders ^[2].

A detail of the trial design may matter for how the results are described. Participants' dysregulated eating episodes were classified as loss-of-control eating rather than binge eating because they did not consistently meet the criteria for eating an objectively large amount, probably because of restricted stomach volume after bariatric surgery ^[2].

Why it matters for patients

The study involved one person who was taking tirzepatide for diabetes and obesity while participating in a brain-stimulation trial. It does not show that tirzepatide or any other GLP-1 drug treats binge-eating disorder, and there is no evidence here about dosing or about what any individual should do ^[1][2].

For people who describe "food noise" — persistent thoughts about food — the report offers a possible physical explanation: a measurable signal in a reward-related brain region that changed while the patient was on the drug. It also suggests that whatever quieting occurred did not hold, at least in this case ^[1][2].

People with binge-eating disorder or bulimia will not find an answer here about whether these drugs help their condition. The researchers say current medications in this class were not designed for that purpose, and that testing the idea properly would require new studies ^[1].

What happens next

The brain recordings came from an ongoing early feasibility trial (registered as NCT03868670) that has enrolled people with treatment-refractory obesity and loss-of-control eating ^[2].

Halpern said he hopes the report inspires rigorous investigation of whether future versions of these drugs could treat certain eating disorders ^[1]. No timeline for redesigned GLP-1 drugs aimed at the brain's reward circuitry has been disclosed ^[1].