Researchers at the Pennington Biomedical Research Center conducted a first-of-its-kind study to provide insights into the mechanisms of action of tirzepatide – a drug known as Zepbound™ – on weight loss with respect to energy expenditure, fat oxidation and calorie intake.
The study, " Tirzepatide did not impact metabolic adaptation in people with obesity, but increased fat oxidation ," published in Cell Metabolism, showed that tirzepatide decreased participants' calorie intake at lunch/dinner by reducing appetite while increasing fat oxidation, thus helping participants to lose weight. However, the drug did not decrease the slowing down of their metabolic rate usually observed with weight loss.
Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, has shown promise in promoting weight loss and improving metabolic health. This randomized, blinded clinical trial involved 55 participants with obesity who were assigned to receive either tirzepatide or a placebo over an 18-week period, alongside a caloric restriction regimen.
The study found that participants receiving tirzepatide experienced significantly greater weight loss compared to the placebo group. Importantly, the reduction in sleeping metabolic rate and 24-hour energy expenditure was comparable between the two groups after adjusting for changes in body weight and composition, indicating that tirzepatide did not affect metabolic adaptation during weight loss.
In other words, when people lose a lot of weight, their bodies often use less energy, which can make it harder to keep the weight off. However, in this study and unlike what has been shown in animal models, people who took tirzepatide did show a slowing down of burning energy after losing weight.
Additionally, tirzepatide significantly reduced 24-hour and sleeping respiratory quotient values, suggesting an increase in fat oxidation and a decrease in carbohydrate and protein oxidation rates. The treatment also led to a notable reduction in food intake among participants.
Dr. Eric Ravussin, LSU Boyd Professor and one of the study's lead researchers, emphasized the potential implications of these findings, "Our research indicates that tirzepatide not only facilitates substantial weight loss but also enhances fat oxidation, but unfortunately, did not decrease the metabolic adaptation usually seen with weight loss. Our results confirmed that tirzepatide is a very efficacious therapeutic option for individuals with obesity."
This study contributes to the growing body of evidence supporting the efficacy of tirzepatide in obesity management and underscores the importance of continued research into its metabolic effects, particularly related to the lack of impact on metabolic adaptation. This study was funded by Eli Lilly and Company, and preliminary findings were presented at the American Diabetes Association's 83rd Scientific Sessions in June 2023.
In addition to Dr. Ravussin, other authors on the study from Pennington Biomedical included Dr. Corby Martin, Dr. Robbie Beyl, Dr. Frank Greenway, and Dr. Guillermo Sanchez-Delgado.
"Our team is proud to be at the forefront of research that can truly change lives," said Dr. John Kirwan, Pennington Biomedical Executive Director. "Tirzepatide, along with other GLP-1 receptor agonists, are showing real promise not only for weight loss, but also for helping people manage their health in smarter, more effective ways."
