Tirzepatide (brand names Mounjaro·zepbound), which has drawn global attention as a treatment for diabetes and obesity, may reduce obsession with and impulses toward food, a study found. But by directly observing actual brain activity, researchers also noted that this effect may not last and could fade over time.
A research team at the Perelman School of Medicine at the University of Pennsylvania implanted electrodes in the brains of patients with obesity and published on the 18th in the journal Nature Medicine findings that recorded in real time the brain signals related to appetite and impulse control. It is the first case to directly measure how tirzepatide changes activity in the human brain, particularly in the nucleus accumbens, which governs impulses.
Tirzepatide acts on the glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors and is known to lower blood sugar and reduce body weight. Many users say they "think about food less," but there has been little scientific evidence of what changes actually occur in the brain.
The team inserted electrodes into the brains of three patients with obesity who suffer from binge eating or loss-of-control eating and conducted a clinical trial to reduce appetite with high-frequency stimulation. Among them, a 60-year-old female patient was already taking tirzepatide for diabetes treatment, and this gave the researchers a rare opportunity to confirm in real time how the drug affects brain signals.
Measurements through the electrodes showed that early in tirzepatide treatment, the patient's obsession with food nearly disappeared, and binge-eating–related signals previously observed in the nucleus accumbens were barely detected. The nucleus accumbens is a brain region that activates when we feel pleasure or satisfaction and is a key area that drives impulses toward food. The patient also said, "My thoughts about food have completely disappeared." The researchers interpreted the results as showing that "the drug appeared to quell the impulse signals of the reward center."
However, after about five months, signals in the nucleus accumbens rose again, and the obsession with food recurred. The team said, "The drug does suppress binge impulses, but the effect is not sustained," adding, "It may not be sufficient as a long-term impulse control therapy."
By contrast, other study participants who did not take tirzepatide consistently showed high nucleus accumbens signals. This supports that the reduction in brain signals observed only in the 60-year-old female participant was due to the drug.
The researchers emphasized that while GLP-1 and GIP drugs are highly effective for blood sugar control and weight loss, there are limits to solving brain-based behavioral problems such as obsession with food or binge impulses with current drugs alone.
Simon Cork, a lecturer at Anglia Ruskin University in the United Kingdom who was not involved in the study, said, "This study is methodologically very interesting, but it must be made clear that it focused on a single patient with a very specific condition related to obesity," adding, "It should not be generalized to the entire population."
Casey H. Halpern, who led the study, said, "This study provides important clues to understanding how tirzepatide acts in the brain," while adding, "To apply this drug to diseases other than type 2 diabetes and obesity, we need to understand the brain mechanism more clearly. Until we understand the mechanism better, it is premature to call GLP-1 and GIP inhibitors a 'miracle drug' for diseases other than type 2 diabetes and obesity."
References
Nature Medicine (2025), DOI: https://doi.org/10.1038/s41591-025-04035-5