Visceral fat reduction may contribute to liraglutide CV benefits
medwireNews: A randomized trial demonstrates significant reductions in visceral adipose tissue (VAT) in people with obesity but without diabetes taking the glucagon-like peptide (GLP)-1 receptor agonist liraglutide.
Ian Neeland (University Hospitals Harrington Heart and Vascular Institute, Cleveland, Ohio, USA) and co-researchers note “the emerging recognition of visceral and ectopic fat as important cardiovascular risk factors.”
They write: “[O]ur findings suggest that reductions in visceral fat and hepatic fat could be mechanisms underpinning the cardiovascular disease risk benefit that has been seen with liraglutide in patients with type 2 diabetes.”
The team’s study involved 128 people (average age 50.2 years, 92% female) who completed 40 weeks of randomly assigned treatment with liraglutide 3.0 mg/day or placebo. The participants all had at least three metabolic syndrome components, including obesity, but none had diabetes, and they undertook a diet (500 kcal deficit) and received physical activity counseling.
During treatment, participants taking liraglutide reduced their VAT by an average of 12.49%, compared with just 1.63% for those taking placebo (10.86 percentage point difference), equating to a VAT loss of 0.53 versus 0.10 L. This effect was consistent regardless of people’s age, sex, race, and BMI, and whether they had prediabetes.
Compared with placebo, treatment with liraglutide also reduced total body fat by an average of 8.64%, abdominal subcutaneous adipose tissue (SAT) by 9.10%, and lower body adipose tissue by 8.66%. In addition, there was a 33.00% difference in liver fat, due to a 20.63% rise in the placebo group and a 12.37% fall in the liraglutide group.
Bodyweight decreased by an average of 5.40% more with liraglutide than placebo, and this was more strongly correlated with total body fat and abdominal SAT than with VAT and liver fat, the team notes.
“This could suggest a partially weight-independent effect of GLP-1 receptor agonism on body fat distribution,” they say.
In a commentary accompanying the report in The Lancet Diabetes & Endocrinology, Kishore Gadde and Steven Heymsfield, both from Pennington Biomedical Research Center in Baton Rouge, Louisiana, USA, dispute this suggestion, noting that “VAT is rapidly mobilised during periods of negative energy balance.”
They explain: “Lifestyle interventions leading to 7% weight loss also report relatively large reductions in VAT, and thus liraglutide’s effects on this highly lipolytic compartment might not be related to its pharmacological mechanisms of action.”
However, the commentators commend the study, saying: “Endpoints such as changes in VAT and liver fat have far more clinical relevance and pathophysiological implications than changes in bodyweight or BMI, typical primary endpoints in randomised, controlled trials of anti-obesity drugs.
“Advances in imaging methods now make it feasible to move beyond these classical primary endpoints towards inclusion of adipose tissue compartments and ectopic lipids as key outcome variables in future trials of new weight loss medicines.”
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