A randomized controlled trial investigating the effect of liraglutide on self-reported liking and neural responses to food stimuli in participants with obesity.

Background/objectives: Obesity is a complex condition and the mechanisms involved in weight gain and loss are not fully 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 liking. Here we investigated the effects of liraglutide on food liking and the cerebral correlates of liking in OB.

Subjects/methods: This study was a randomized, single-center, double-blind, placebo-controlled, parallel group, prospective clinical trial. 73 participants with OB and without diabetes following a multidisciplinary weight loss program, were randomly assigned (1:1) to receive liraglutide 3.0 mg (37.40 ± 11.18 years old, BMI = 35.89 ± 3.01 kg) or a placebo (40.04 ± 14.10 years old, BMI = 34.88 ± 2.87 kg) subcutaneously once daily for 16 weeks.

Interventions/methods: We investigated liking during food consumption. 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 during the pre- and post-intervention sessions.

Results: None of the effects involving the intervention factor reached significance when comparing liking between the pre- and post-intervention sessions or groups. Liking during food reward consumption was associated with the activation of the ventromedial prefrontal cortex (vmPFC) and the amygdala. The liraglutide group lost more weight (BMI post-pre = -3.19 ± 1.28 kg/m) than the placebo group (BMI post-pre = -0.60 ± 1.26 kg/m).

Conclusions: These results suggest that liraglutide leads to weight loss without self-report or neural evidence supporting a concomitant reduction of food liking in participants with OB.