Tirzepatide temporarily suppresses compulsive food cravings in patients with obesity

A recent study has shown that tirzepatide can temporarily reduce neural activity associated with compulsive food cravings in people with obesity. This effect was observed using electrodes implanted in the brain, but over time, the drug’s impact diminished. This highlights the need for more targeted and long-lasting treatments for overeating and impulsivity.

New insights into how tirzepatide works

The ability to monitor deep brain activity in a person with obesity and loss of control over eating has given researchers a new perspective on how tirzepatide (marketed as Mounjaro and Zepbound) interacts with the brain. Recordings revealed that the drug lowers activity in the brain’s reward center—an area linked to obsessive thoughts about food and compulsive cravings. However, this reduction in activity was only temporary.

Researchers note that tirzepatide is an agonist of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors, originally developed to treat type 2 diabetes. Early data suggest it may also help with impulse control disorders, including binge eating. However, a new study from the Perelman School of Medicine at the University of Pennsylvania warns that current GLP-1 and GIP inhibitors are not yet optimized for treating such conditions and require further research. The results were published in Nature Medicine.

Loss of control over eating: the scope of the problem

Loss of control over eating is widespread among people with obesity and eating disorders. Binge eating disorder (BED) is the most common eating disorder in the US, affecting more than 3 million people. Those with BED often find it difficult to stop eating and continue even after feeling full.

Key brain regions that regulate eating behavior include the hypothalamus and the nucleus accumbens (NAc)—a crucial reward center responsible for motivation, pleasure-seeking, and impulse control. Studies show that in people with obesity and BED, signaling in the NAc and related pathways is disrupted.

Even without a BED diagnosis, up to 60% of people with obesity experience constant “food noise”—a persistent stream of thoughts about food that can lead to stress and maladaptive behaviors such as overeating or loss of control. This phenomenon is also common in bulimia and anorexia. Research links binge eating to a higher risk of suicide among people with obesity and eating disorders, likely due to impulsivity and emotional instability.

Clinical case: unique observations

The study describes in detail the case of a 60-year-old woman with severe, treatment-resistant obesity and persistent “food noise.” She suffered from obsessive thoughts about food, which led her to order takeout or snack throughout the day despite efforts to stop. She often ate to the point of discomfort, especially craving sweet and salty foods like cakes, fast food, and French fries. She also had type 2 diabetes, and a previously prescribed GLP-1 inhibitor (dulaglutide) did not help her lose weight or reduce her food cravings.

After multiple unsuccessful treatments—including bariatric surgery, medications, and behavioral therapy—she joined a clinical trial in which electrodes were implanted in her brain. This allowed future detection and interruption of food cravings before they escalated into binge episodes.

Previous research had identified a distinctive pattern of electrical activity in the NAc that appears just before a person becomes fixated on food and experiences an overwhelming urge to overeat. This activity does not occur with normal hunger before meals. Pilot studies showed that high-frequency stimulation of the NAc at the onset of these signals can stop binge eating episodes.

Experiment process and results

In the current study, four participants with obesity and loss of control over eating had intracranial electroencephalographic (iEEG) electrodes implanted. The device recorded NAc activity when participants encountered foods that triggered binge episodes.

After establishing baseline responses for each participant, the electrodes were programmed to deliver high-frequency stimulation when signals associated with food cravings were detected. Over six months, participants reported a significant reduction in loss-of-control feelings and fewer binge episodes.

Before surgery, one participant was prescribed tirzepatide to manage type 2 diabetes after the first GLP-1 inhibitor proved ineffective. The dose was gradually increased to the maximum before and after electrode implantation to reduce the risk of post-surgical infections. This created a unique opportunity to observe, in real time, how tirzepatide affects brain signals linked to food cravings.

After reaching the full tirzepatide dose and electrode implantation, the patient’s obsessive thoughts about food disappeared, which was confirmed by reduced NAc activity. However, about five months later, the previous NAc activity and intense “food noise” returned, indicating the temporary nature of tirzepatide’s effect.

Other participants who did not take tirzepatide continued to show elevated NAc activity and frequent obsessive thoughts about food, consistent with previous observations. The significant reduction in signals seen only in one participant suggests that tirzepatide temporarily suppressed this activity.

Outlook and conclusions

GLP-1 and GIP inhibitors have proven effective for controlling blood sugar in type 2 diabetes and for weight loss in obesity. The new study suggests they may also help manage obsessive thoughts about food and binge eating, but not in their current form.

Although the study examined data from only one patient taking tirzepatide, it provides compelling evidence of how GLP-1 and GIP inhibitors alter electrical signals in the brain. These findings should encourage further research to develop safer and longer-lasting treatments, better tailored to the impulsive traits of obesity and related eating disorders.