Brain may put brakes on liraglutide weight loss effect
medwireNews: A small neuroimaging study suggests that taking liraglutide over the medium to long term may provoke a counter-regulatory response in the brain, diminishing the medication’s weight loss effect.
Glucagon-like peptide (GLP)-1 receptor agonists used at the approved doses for diabetes decreased reward-related brain activation in previous short-term studies, conducted over 10–17 days.
For the current study, Olivia Farr (Beth-Israel Deaconess Medical Center, Boston, Massachusetts, USA) and colleagues titrated up to the 3 mg/day dose approved for obesity over 4 weeks and assessed brain activity at the end of week 5, “just before any plateauing weight loss phenomenon would start.”
The double-blind randomized crossover trial involved 11 men and nine women with obesity who took liraglutide or placebo for 5 weeks, and then the alternative treatment, with a minimum 3-week washout period between. While taking liraglutide, they lost an average of 2.5% of their starting bodyweight, compared with a 0.19% increase when taking placebo.
When the study participants underwent functional magnetic resonance imaging, they showed no differences in brain activation in response to food versus non-food images according to whether they had been taking liraglutide or placebo over the preceding 5 weeks.
However, when the findings were corrected for BMI or weight, the participants had significantly greater activation in the right orbitofrontal cortex (OFC) in response to food versus non-food images when they were taking liraglutide, as compared with placebo.
The researchers say that “[t]he OFC is well known to increase in response to rewarding stimuli as well as to pleasantness ratings of food images.”
They highlight that liraglutide use led to the loss of an average 2.7% of the participants’ bodyweight relative to placebo, and the effects on brain activation were in the opposite direction to those seen in the short-term studies.
“Thus, we believe that this is a counter-regulatory mechanism where weight loss is causing early increases in activations of the OFC to food cues, leading to the eventual weight loss plateau observed with this and other weight loss medications,” the team writes in Diabetes, Obesity and Metabolism.
In a previous study, the GLP-1 receptor agonist effects on brain activation disappeared at 12 weeks, but Farr and team note that the control medication in that study was insulin rather than placebo, and that the researchers did not control for BMI or bodyweight, “and it is thus impossible to tell whether they might have had similar brain changes” to those seen in the present study had these factors been accounted for.
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