Effect of liraglutide on thigh muscle fat and muscle composition in adults with overweight or obesity: Results from a randomized clinical trial

Author:

Pandey Ambarish1,Patel Kershaw V.2,Segar Matthew W.3,Ayers Colby1,Linge Jennifer45,Leinhard Olof D.45,Anker Stefan D.6,Butler Javed78,Verma Subodh9,Joshi Parag H.1,Neeland Ian J.10

Affiliation:

1. University of Texas Southwestern Medical Center Dallas TX USA

2. Department of Cardiology Houston Methodist DeBakey Heart & Vascular Center Houston TX USA

3. Department of Cardiology Texas Heart Institute Houston TX USA

4. AMRA Medical and Linköping University Linköping Sweden

5. Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine Linköping University Linköping Sweden

6. Department of Cardiology (CVK), Berlin Institute of Health Center for Regenerative Therapies (BCRT), and German Centre for Cardiovascular Research (DZHK) Partner Site Berlin Charité Universitätsmedizin Berlin Germany

7. Baylor Heart and Vascular Institute Baylor University Medical Center Dallas TX USA

8. Department of Medicine University of Mississippi School of Medicine Jackson MS USA

9. St. Michael's Hospital University of Toronto Toronto ON Canada

10. Harrington Heart and Vascular Institute University Hospitals Cleveland Medical Center and Case Western Reserve University School of Medicine Cleveland OH USA

Abstract

AbstractBackgroundExcess muscle fat is observed in obesity and associated with greater burden of cardiovascular risk factors and higher risk of mortality. Liraglutide reduces total body weight and visceral fat but its effect on muscle fat and adverse muscle composition is unknown.MethodsThis is a pre‐specified secondary analysis of a randomized, double‐blind, placebo‐controlled trial that examined the effects of liraglutide plus a lifestyle intervention on visceral adipose tissue and ectopic fat among adults without diabetes with body mass index ≥30 kg/m2 or ≥27 kg/m2 and metabolic syndrome. Participants were randomly assigned to a once‐daily subcutaneous injection of liraglutide (target dose 3.0 mg) or matching placebo for 40 weeks. Body fat distribution and muscle composition was assessed by magnetic resonance imaging at baseline and 40‐week follow‐up. Muscle composition was described by the combination of thigh muscle fat and muscle volume. Treatment difference (95% confidence intervals [CI]) was calculated by least‐square means adjusted for baseline thigh muscle fat. The association between changes in thigh muscle fat and changes in body weight were assessed using Spearman correlation coefficients. The effect of liraglutide versus placebo on adverse muscle composition, denoted by high thigh muscle fat and low thigh muscle volume, was explored.ResultsAmong the 128 participants with follow‐up imaging (92.2% women, 36.7% Black), median muscle fat at baseline was 7.8%. The mean percent change in thigh muscle fat over median follow‐up of 36 weeks was −2.87% among participants randomized to liraglutide (n = 73) and 0.05% in the placebo group (absolute change: −0.23% vs. 0.01%). The estimated treatment difference adjusted for baseline thigh muscle fat was −0.24% (95% CI, −0.41 to −0.06, P‐value 0.009). Longitudinal change in thigh muscle fat was significantly associated with change in body weight in the placebo group but not the liraglutide group. The proportion of participants with adverse muscle composition decreased from 11.0% to 8.2% over follow‐up with liraglutide, but there was no change with placebo.ConclusionsIn a cohort of predominantly women with overweight or obesity in the absence of diabetes, once‐daily subcutaneous liraglutide was associated with a reduction in thigh muscle fat and adverse muscle composition compared with placebo. The contribution of muscle fat improvement to the cardiometabolic benefits of liraglutide requires further study.

Funder

Novo Nordisk

Publisher

Wiley

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