Liraglutide May Reduce Brain’s Reward Response to High-Fat Foods

BOSTON — The brain scans of adults with diabetes showed that the drug liraglutide reduced the psychic rewards associated with highly desirable high-fat, high-calorie foods.

Liraglutide decreased reward activations in the cortex in response to images of highly desirable foods, such as cake, pastries, and fried food, compared with less desirable foods, such as fruits, vegetables, and other low-calorie, low-fat foods, said study co-investigator Olivia Farr, PhD, an instructor in medicine at Beth Israel Deaconess Medical Center and Harvard Medical School in Boston. She added that these findings could mean that liraglutide makes people pay more attention to what they are eating, particularly calorie-dense foods that are high in fat.

“This decreased activation means that individuals on liraglutide find highly desirable foods less attention-grabbing and less rewarding than they typically would without liraglutide,” Dr Farr said in a press release. “Thus, this medication may prove to be better for weight loss for people who tend to eat more high-fat food as a reward, such as when they are stressed. Our study identifies neural targets for more effective weight loss therapeutics in the future.”

Dr Farr presented the results at ENDO 2016.

Injectable liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist that is FDA-approved for treatment of type 2 diabetes (Victoza, Novo Nordisk). Research suggests that a 1.8-mg dose can induce weight loss in people with type 2 diabetes, while a 3.0-mg dose is FDA-approved for weight management in obese and overweight people with at least 1 weight-related comorbidity (Saxenda, Novo Nordisk).

Based on animal studies, Dr Farr and her team hypothesized that liraglutide may work directly in the brain to decrease weight. They assessed 22 human brain tissue samples using immunohistochemistry for the presence of GLP-1 receptors and found evidence, for the first time, that GLP-1 is expressed in human brains. Further, they found that the hormone is expressed on the cerebral cortex, not just the brainstem and hypothalamus.

The researchers then performed a randomized, placebo-controlled crossover trial involving 18 adults with type 2 diabetes. Participants were assigned to 17 days of increasing doses (0.2 mg to 1.2 mg to 1.8 mg) of liraglutide or placebo. Following a 3-week washout period, the same participants received 17 days of the opposite treatment. On day 17, participants viewed images of different foods while undergoing functional magnetic resonance imaging (fMRI) brain scanning.

“Liraglutide decreased activation in the parietal cortex to these highly desirable food cues,” Dr Farr said during a press conference at ENDO 2016. “It is selectively decreasing attention or attractiveness to these high-calorie or high-fat food cues.”

Dr Farr said her team is planning more studies to determine if the results remain consistent at the 3.0-mg liraglutide dose. Researchers also hope to learn if there are individual differences in the brain’s response to liraglutide and whether any compensatory brain activations may arise at higher doses to curb weight loss.

Reference

1. Farr OM, Sofopoulos M, Tsoukas MA, et al. OR15-2: GLP-1 Receptors Exist in the Parietal Cortex, Hypothalamus, and Medulla of Human Brains and the GLP-1 Analog Liraglutide Administered in the Context of a Cross-over, Randomized, Placebo-Controlled Trial Alters Brain Activity in Response to Highly Desirable Food Cues in Individuals with Diabetes. Presented: ENDO 2016; April 1-4, 2016; Boston, MA.