Effect of liraglutide on muscle fat infiltration in adults with overweight or obesity: a randomized clinical trial

Presented at the EASD annual meeting 2022 by: Ambarish Pandey, MD- Dallas, TX ,USA

Introduction and methods

Traditionally, overall obesity is defined as BMI ≥30 kg/m2. However, obesity is a heterogenous condition with different body compositions and fat distributions. Regional fat depots play an important role in the pathophysiology that is attributed to obesity. In addition to abdominal adiposity depots, fat tissue in and around skeletal muscles has important pathophysiological effects.

This was demonstrated in a recent study using data from the Health ABC cohort. Higher levels of intra- and intermuscular fat were associated with metabolic syndrome, obesity and increased visceral adipose tissue (VAT) depots. When looking at outcomes, only intramuscular fat was associated with higher risk of HF (17% higher risk per 1 SD higher amount of intramuscular fat).

The aim of this study was to examine whether muscle fat infiltration -associated with increased risk of HF- is modifiable by weight loss therapies.

Recently, a randomized double-blind trial was performed in which the effects of liraglutide on visceral and ectopic fat was investigated in 182 adults with overweight and obesity (BMI ≥30 kg/m2 or BMI ≥27 kg/m2 plus metabolic syndrome) without DM and at high CV risk. A 11% greater reduction in VAT depots with liraglutide was observed.

This was a pre-specified secondary outcome analysis of the previously mentioned RCT with liraglutide vs. placebo. Patients had baseline and follow-up assessment of regional fat depots using 3D whole body MRI and also had cardiometabolic markers measured at baseline and follow-up.

Primary outcome of this analysis was change in muscle fat infiltration from baseline to follow-up. Muscle fat was determined as the average proportion of fat in viable muscle tissue of the bilateral anterior thigh.

Main results

• Mean change in muscle fat infiltration in the placebo group was 0.29% vs. -3.23% in the liraglutide group.
• Change in muscle fat infiltration was associated with change in VAT and abdominal subcutaneous adipose tissue, but not with total lean thigh muscle.
• Change in muscle fat infiltration was associated with changes in fasting plasma glucose, CRP and NT-proBNP
• There was a 30% reduction in the proportion of patients with adverse muscle composition (low muscle volume and high muscle fat infiltration) in the group on liraglutide vs. no change in the proportion of patients with adverse muscle composition in those on placebo.

Conclusion

Once daily subcutaneous liraglutide reduced mean anterior thigh muscle fat infiltration compared with placebo independent of changes in thigh muscle volume.

Pandey further concluded: “The contribution of muscle fat infiltration improvement to the cardiometabolic benefits of liraglutide requires further study.”

• Our reporting is based on the information provided at the EASD annual meeting -