Tirzepatide reduces food intake and appetite, and affects brain functioning, more than placebo and liraglutide: Study

Researchers found that tirzepatide, a medication primarily used for treating type 2 diabetes and weight loss, reduced body weight, food intake and many measures of appetite more than placebo and liraglutide. These results were recently published in Nature Medicine in the study titled “Tirzepatide on ingestive behavior in adults with overweight or obesity: a randomized 6-week phase 1 trial.”

Pennington Biomedical’s Dr. Owen Carmichael, Director of the Biomedical Imaging Center, and Dr. Corby Martin, Director of the Ingestive Behavior, Weight Management & Health Promotion laboratory, along with collaborators from research institutes across the country, evaluated tirzepatide against liraglutide and a placebo. Significant results started emerging on the third week of the six-week trial, and participants taking tirzepatide ate 72% less calories than they did before taking the medication. Tirzepatide decreased numerous measures of appetite or the drive to eat, including things like hunger and food cravings. Interestingly, tirzepatide did not increase the intent to restrict food intake, which is a novel finding.

“For people to lose weight, they typically spend a great deal of effort trying to limit how much they eat,” said Dr. Martin. “Tirzepatide promotes weight loss and large reductions in food intake, with apparently little volitional effort among participants. This is indeed novel.”

Study participants were examined with functional magnetic resonance imaging (fMRI) to analyze brain activity while being shown pictures of a variety of foods, including cakes, ice cream, and other foods high in fat and sugar. The brain scans demonstrated that individuals taking tirzepatide exhibited reduced activity in hunger and reward sensitive brain areas while viewing such high-fat, high-sugar foods.

“We believe this may be the first data suggesting that tirzepatide modifies brain functioning in eating-relevant brain regions more than liraglutide does,” said Dr. Carmichael. “It was already well established that tirzepatide promotes greater weight loss on average than liraglutide does, but it was not entirely clear why. Our data suggests that one reason for tirzepatide’s greater efficacy could by that it has a great greater effect on brain function.

Unlike semaglutide or liraglutide that only activate the GLP-1 receptor, the dual agonist tirzepatide works on the GLP-1 and GIP receptors, two important hormone pathways that help control hunger. As of today, there are no medications on the market that purely target GIP, which may indicate a new direction for research possibilities.

“For those living with obesity or diabetes, the field of weight loss medications is at an inflection point, in which we are seeing results improve further as new products are tested and become available,” said Dr. John Kirwan, Executive Director of Pennington Biomedical. “I congratulate Drs. Carmichael and Martin, along with their collaborators, on this new study, as the data indicates that tirzepatide is highly effective at managing appetite and food intake and has measurable effects on brain responses to food.”

Reference:

Martin, C.K., Carmichael, O.T., Carnell, S. et al. Tirzepatide on ingestive behavior in adults with overweight or obesity: a randomized 6-week phase 1 trial. Nat Med (2025). https://doi.org/10.1038/s41591-025-03774-9