Newer obesity drugs alter appetite feedback control, allow greater long-term weight loss
Key takeaways:
- A person’s calorie intake and expenditure are under biological control.
- GLP-1 receptor agonists and similar obesity medications are aimed at affecting appetite, thereby lowering a person’s calorie equilibrium.
Incretin-based obesity medications are targeted at appetite signaling in a person’s brain, altering energy equilibrium and allowing greater weight loss than lifestyle intervention, according to a speaker.
Data presented during a session at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease showed how various obesity treatment strategies affect energy balance differently. Lifestyle interventions such as calorie-restricted diets do not change appetite signaling in the brain, leading to energy intake increasing gradually over time. However, newer obesity medications such as tirzepatide (Zepbound, Eli Lilly) can change appetite signaling to lower a person’s caloric equilibrium, allowing them to lose more weight compared with lifestyle change alone.
“[With these medications], you’re changing the feedback control strength of how weight loss influences appetite,” Kevin D. Hall, PhD, chief of the integrative physiology section in the laboratory of biologic monitoring at the National Institute of Diabetes and Digestive and Kidney Diseases, said during a presentation.
The number of calories a person consumes and expends is not independent of one another, according to Hall. He discussed how various signals from the body act to control one’s appetite, or calorie intake, and expenditure. Hall described the point where caloric intake meets caloric expenditure as a person’s body weight equilibrium point.
A person burns approximately 25 kcal less per day with every 1 kg of body weight they lose, according to Hall. Conversely, a paper published in Obesity in 2016 found appetite increased by 95 kcal per day with every 1 kg of weight lost.
Lifestyle changes such as a calorie-restricted eating pattern are unable to shift a person’s appetite, Hall said, noting that while a person may lower their caloric intake in the short term, continuing restricting calories requires a fight against increasing appetite as weight is lost. Over a long-term period, Hall said, a person will achieve their energy balance again by increasing caloric intake, causing weight loss to plateau.
In findings published in the American Journal of Clinical Nutrition, researchers modeled energy intake and expenditure using data from the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) trial, where participants engaged in an intensive lifestyle intervention to lower caloric intake by 25% for 2 years. In the study, reductions in body fat and body weight were achieved for about 1 year before plateauing for the reminder of the study. Caloric intake for the study group dropped at the start of the study before gradually increasing.
“Initially, you haven’t lost any weight and there’s no signal in that appetite feedback control loop,” Hall said. “The more weight you lose, the greater the battle. Appetite is much greater at the weight-loss plateau than it was at the beginning.”
Unlike with lifestyle intervention, newer incretin-based obesity medications are targeting signals in the brain influencing appetite. A paper published in Obesity modeled changes in energy expenditure and intake with tirzepatide 10 mg. The model estimated adults using tirzepatide lower their energy intake by 1,200 kcal per day at 3 months and maintain a 500 kcal per day reduction in energy intake at 2 years.
While adults using tirzepatide may reach a calorie intake and weight-loss plateau at 2 years, Hall noted that is similar to what is seen with Roux-en-Y gastric bypass and better than the 1-year plateau seen with lifestyle intervention.
“By dampening the appetite feedback control circuit, some of the newer [drugs] prolong the period needed to reach the plateau, losing even more weight,” Hall said.
References:
Guo J, et al. Am J Clin Nutr. 2018;doi:10.1093/ajcn/nqx080.
Hall KD, et al. Obesity. 2024;doi:10.1002/oby.24027.
Polidori D, et al. Obesity. 2016;doi:10.1002/oby.21653.
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Hall KD. Session 20: Diets and weight loss. Presented at: World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease; Dec. 12-14, 2024; Los Angeles.
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