Mechanistic Insights into Tirzepatide’s Transient Influence on Food Cravings

In a case study from the University of Pennsylvania Perelman School of Medicine, tirzepatide produced short-lived suppression of reward-region activity linked to food cravings in intracranial recordings from a single patient.

Intracranial recordings reported changes in the nucleus accumbens and adjacent reward-related regions. The principal signal change was a reduction in delta–theta activity that coincided with episodes of food preoccupation and craving.

That suppression was not permanent; nucleus accumbens signaling, which quieted during full-dose exposure, began to re-emerge over a multi-month follow-up.

Important caveats limit generalizability. The finding derives from a single patient with implanted electrodes, a complex treatment history, and a surgical context that may bias selection. Electrode placement and perioperative factors can influence recorded signals, and no controlled, longitudinal behavioral endpoints were reported to confirm lasting changes in eating behavior.