TOPLINE:

A first-in-human study suggested that tirzepatide — a dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist — modulated abnormal activity in the brain’s nucleus accumbens, thereby reducing food cravings and inducing weight loss in a patient with severe obesity.

METHODOLOGY:

• Brain signals (known as delta-theta activity) in the nucleus accumbens have previously been linked to food preoccupation and craving.
• Researchers analyzed brain activity in the nucleus accumbens in three patients with severe obesity and difficulty controlling their eating.
• In two of the patients, they used therapeutic deep brain stimulation on this area and looked at the effect on food preoccupation and cravings.
• They also looked at brain signals of the third patient who had been given tirzepatide to manage diabetes after bariatric surgery.

TAKEAWAY:

• Deep brain stimulation of the nucleus accumbens reduced the brain signals and food preoccupation during stimulation in the two patients, preliminarily validating the brain signal as a biomarker of food preoccupation and cravings.
• The participant taking tirzepatide also experienced a reduction in brain signals and food cravings, particularly in months 2-4 after surgery during dose escalation of the drug.
• However, the brain signals and subsequent food preoccupation returned a few months later in this patient despite taking the maximum dose of tirzepatide, suggesting that relief from the cravings was only temporary.

IN PRACTICE:

Developing new ways to treat patients with obesity who are experiencing “food noise” or thinking about food constantly, “is of the utmost importance,” said the principal author in a press release. “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. In fact, their impact on human brain activity has only begun to be studied.”

In an independent comment for the Science Media Centre, London, England, Simon Cork, PhD, Anglia Ruskin University, Cambridge, England, also cautioned, “While this study is methodologically very interesting, it has to be clear that this is only one patient with a very specific condition that is associated with obesity and so shouldn’t necessarily be generalized to the entire population.”

SOURCE:

The study, led by Casey Halpern, MD, Perelman School of Medicine, University of Pennsylvania, Philadelphia, was published online in Nature Medicine.

LIMITATIONS:

As a single uncontrolled case study, this report has a number of limitations, including a potential lack of generalizability to other incretin-based therapies. Given the potential compulsive component in patients with dysregulated eating behaviors, the delta-theta biomarker may not be applicable to the broader population with obesity.

In addition, the authors of the study could not determine whether the effects of tirzepatide were due to direct action in the nucleus accumbens. The observed electrophysiologic changes may be attributable to confounding factors such as postoperative recovery, elapsed time since surgery, or unrelated behavioral changes.

DISCLOSURES:

The work was supported by the US National Institutes of Health. Halpern and other coauthors filed a provisional patent application related to sensing accumbens activity to guide the treatment of obesity and related disorders.

Marilynn Larkin, MA, is an award-winning medical writer and editor whose work has appeared in numerous publications, including Medscape Medical News and its sister publication MDedge, The Lancet (where she was a contributing editor), and Reuters Health.