Tirzepatide’s Impact on Brain Activity Explored in Obesity Case Study
A unique opportunity to observe deep brain activity in a person with obesity and loss of control eating provided new insight into how tirzepatide, sold as Mounjaro and Zepbound, interacts with the brain. Recordings showed that the medication reduced activity in the brain’s reward center, a region linked to food noise and compulsive cravings, although this reduction did not last.
researchers noted that tirzepatide is a glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist originally created for Type 2 diabetes. Early findings suggest it may also help with conditions related to impulse control, including binge eating disorder. Though, the new report from the Perelman School of Medicine at the University of Pennsylvania cautions that current GLP-1 and GIP inhibitors may not be fully optimized for treating these behaviors and warrant more investigation. The case study appears in Nature Medicine.
“This study offers major insights into how these drugs may work inside the brain and will guide us as we explore new indications,” said senior author Casey H. Halpern, MD, a professor of Neurosurgery and head of the Division of Stereotactic and Functional Neurosurgery. “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.”
Understanding Loss of Control Eating and Food Noise
Loss of control eating is widespread, affecting many people with obesity as well as multiple eating disorders. Binge eating disorder (BED) is considered the most common eating disorder in the United States, impacting more than 3 million individuals. People with BED often feel unable to stop eating and continue long after they feel full.
Critical brain regions involved in regulating eating behaviour include the hypothalamus and the nucleus accumbens (NAc), which serves as a key reward center. The NAc helps govern motivation, pleasure-seeking behaviors, and impulse control.Studies have shown that in people with obesity and BED, signaling within the NAc and related circuits becomes disrupted.
Even without a diagnosis of BED,up to 60 percent of individuals with obesity experience persistent “food noise,” a constant stream of thoughts about food that can lead to distress and maladaptive patterns such as bingeing or loss of control eating. Food noise is also common in bulimia nervosa and anorexia nervosa. Research has linked binge eating with an increased risk of suicide among people with obesity and eating disorders,likely tied to impulsive traits and emotional dysregulation.
“Developing new ways to treat these patients is of the utmost importance,” said Halpern. “While many individuals taking GLP-1 and GIP inhibitors report a reduction in food noise, these medications are not FDA-approved to treat food preoccupation and its related impulsivity. Actually, their impact on human brain activity has only begun to be studied.”
A Patient’s Struggle With severe Obesity and Food Noise
A 60-year-old woman referred to as “Participant 3” in the study was living with severe, treatment-resistant obesity and persistent food noise. She described constant, intrusive thoughts about food that frequently led her to order takeout or snack throughout the day, even when she tried to stop. She often ate until she felt uncomfortably