This Obesity Drug Cuts Calorie Intake by 72% Without Dieting

Pennington Biomedical researchers and their collaborators observed decreased activity in the brain regions responsible for hunger and reward in patients treated with tirzepatide.

A recent study has shown that tirzepatide, a medication commonly prescribed for type 2 diabetes and weight management, led to greater reductions in body weight, food consumption, and various appetite-related measures when compared to both a placebo and the drug liraglutide. The findings were recently published in Nature Medicine.

Researchers from Pennington Biomedical, including Dr. Owen Carmichael (Director of the Biomedical Imaging Center) and Dr. Corby Martin (Director of the Ingestive Behavior, Weight Management & Health Promotion Laboratory), worked with colleagues from multiple institutions across the United States to conduct the trial. During the six-week study, significant changes began to appear as early as the third week.

Participants who received tirzepatide consumed 72% fewer calories than they had before starting the treatment. The medication reduced several key drivers of eating behavior, such as hunger and food cravings. Notably, it did not increase participants’ conscious efforts to limit their food intake, which researchers highlighted as a particularly novel observation.

“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.”

Brain Imaging Reveals Altered Hunger Responses

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, which 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: “Tirzepatide on ingestive behavior in adults with overweight or obesity: a randomized 6-week phase 1 trial” by Corby K. Martin, Owen T. Carmichael, Susan Carnell, Robert V. Considine, David A. Kareken, Ulrike Dydak, Richard D. Mattes, David Scott, Sergey Shcherbinin, Hiroshi Nishiyama, Alastair Knights, Shweta Urva, Lukasz Biernat, Edward Pratt, Axel Haupt, Mark Mintun, Diana Otero Svaldi, Zvonko Milicevic and Tamer Coskun, 24 June 2025, Nature Medicine.
DOI: 10.1038/s41591-025-03774-9

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