PDF(Pubmed)
Abstract：
BACKGROUND: Excess 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.
METHODS: This 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.
RESULTS: Among 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.
CONCLUSIONS: In 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.
METHODS: This 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.
RESULTS: Among 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.
CONCLUSIONS: In 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.
摘要：
背景：在肥胖中观察到过量的肌肉脂肪，并且与心血管危险因素的更大负担和更高的死亡风险相关。利拉鲁肽可降低总体重和内脏脂肪，但其对肌肉脂肪和不利肌肉成分的影响尚不清楚。
方法：这是对随机，双盲,安慰剂对照试验，研究了利拉鲁肽加生活方式干预对体重指数≥30kg/m2或≥27kg/m2且无代谢综合征的糖尿病成人内脏脂肪组织和异位脂肪的影响。参与者被随机分配到每天一次皮下注射利拉鲁肽（目标剂量3.0mg）或匹配的安慰剂，持续40周。在基线和40周随访时通过磁共振成像评估体脂分布和肌肉组成。通过大腿肌肉脂肪和肌肉体积的组合来描述肌肉组成。通过针对基线大腿肌肉脂肪调整的最小二乘法计算治疗差异(95%置信区间[CI])。使用Spearman相关系数评估大腿肌肉脂肪的变化与体重变化之间的关联。利拉鲁肽与安慰剂对不利肌肉组成的影响，高大腿肌肉脂肪和低大腿肌肉体积表示，被探索了。
结果：在128名接受随访成像的参与者中（92.2％的女性，36.7%黑色)，基线时肌肉脂肪中位数为7.8%.在随机接受利拉鲁肽（n=73）的参与者中，经过36周的中位随访，大腿肌肉脂肪的平均变化百分比为-2.87％，安慰剂组为0.05％（绝对变化：-0.23％vs.0.01%）。根据基线大腿肌肉脂肪调整后的估计治疗差异为-0.24％（95％CI，-0.41至-0.06，P值0.009）。在安慰剂组而不是利拉鲁肽组中，大腿肌肉脂肪的纵向变化与体重变化显着相关。与利拉鲁肽的随访相比，肌肉成分不良的参与者比例从11.0%下降到8.2%，但安慰剂没有变化。
结论：在一组主要是超重或肥胖且没有糖尿病的女性中，与安慰剂相比,每日一次皮下利拉鲁肽与大腿肌肉脂肪减少和肌肉组成不良相关.肌肉脂肪改善对利拉鲁肽心脏代谢益处的贡献需要进一步研究。
方法：这是对随机，双盲,安慰剂对照试验，研究了利拉鲁肽加生活方式干预对体重指数≥30kg/m2或≥27kg/m2且无代谢综合征的糖尿病成人内脏脂肪组织和异位脂肪的影响。参与者被随机分配到每天一次皮下注射利拉鲁肽（目标剂量3.0mg）或匹配的安慰剂，持续40周。在基线和40周随访时通过磁共振成像评估体脂分布和肌肉组成。通过大腿肌肉脂肪和肌肉体积的组合来描述肌肉组成。通过针对基线大腿肌肉脂肪调整的最小二乘法计算治疗差异(95%置信区间[CI])。使用Spearman相关系数评估大腿肌肉脂肪的变化与体重变化之间的关联。利拉鲁肽与安慰剂对不利肌肉组成的影响，高大腿肌肉脂肪和低大腿肌肉体积表示，被探索了。
结果：在128名接受随访成像的参与者中（92.2％的女性，36.7%黑色)，基线时肌肉脂肪中位数为7.8%.在随机接受利拉鲁肽（n=73）的参与者中，经过36周的中位随访，大腿肌肉脂肪的平均变化百分比为-2.87％，安慰剂组为0.05％（绝对变化：-0.23％vs.0.01%）。根据基线大腿肌肉脂肪调整后的估计治疗差异为-0.24％（95％CI，-0.41至-0.06，P值0.009）。在安慰剂组而不是利拉鲁肽组中，大腿肌肉脂肪的纵向变化与体重变化显着相关。与利拉鲁肽的随访相比，肌肉成分不良的参与者比例从11.0%下降到8.2%，但安慰剂没有变化。
结论：在一组主要是超重或肥胖且没有糖尿病的女性中，与安慰剂相比,每日一次皮下利拉鲁肽与大腿肌肉脂肪减少和肌肉组成不良相关.肌肉脂肪改善对利拉鲁肽心脏代谢益处的贡献需要进一步研究。
