Does GLP-1 receptor agonist liraglutide alter food-related sensory pleasure in patients with obesity? A randomized controlled trial

Abstract

Background/Objectives: Obesity is a complex condition and the mechanisms involved in weight gain and loss are poorly understood. Liraglutide, a GLP-1 receptor agonist, has been demonstrated to successfully promote weight loss in patients with obesity (OB). Yet, it is unclear whether the observed weight loss is driven by an alteration of food reward processing. Here we investigated the effects of liraglutide on cerebral correlates of food-related sensory pleasure in OB. Subjects/Methods: This study was a randomized, single-centre, double-blind, placebo-controlled, parallel group, prospective clinical trial. 73 patients with OB and without diabetes were randomly assigned (1:1) to receive liraglutide 3.0 mg (37.40±11.18 years old, BMI = 35.89 kg ±3.01) or placebo (40.04±14.10 years old, BMI = 34.88 kg ±2.87) subcutaneously once daily, for 16 weeks. They also followed a multidisciplinary weight loss program. Interventions/Methods: We investigated sensory pleasure during food consumption (i.e., “liking”). Participants reported their hedonic experience while consuming a high-calorie food (milkshake) and a tasteless solution. The solutions were administered inside the scanner with a Magnetic Resonance Imaging (MRI)-compatible gustometer to assess neural responses during consumption. The same procedure was repeated for pre- and post-intervention sessions. Results: The liraglutide group lost more weight (BMI post-pre = - 3.19 kg/m2 ±1.28) than the placebo group (BMI post-pre = - 0.60 kg/m2 ±1.26). The sensory pleasure during food reward consumption was associated with the activation of the ventromedial prefrontal cortex (vmPFC) and the amygdala. We did not find any statistically significant difference in the liraglutide group between the pre and post sessions, neither at a subjective level nor at a neural level in terms of reactivity of the vmPFC to the milkshake.Conclusions: These results suggest that liraglutide leads to weight loss without self-report or neural evidence supporting a concomitant reduction of food-related sensory pleasure in patients with from obesity.