BackgroundExcess 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.

中文翻译：

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利拉鲁肽对超重或肥胖成人大腿肌肉脂肪和肌肉成分的影响：随机临床试验的结果

背景在肥胖症中观察到过量的肌肉脂肪，并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良肌肉成分的影响尚不清楚。方法这是对一项随机、双盲、安慰剂对照试验的预先指定的二次分析，该试验检查了利拉鲁肽加生活方式的影响体重指数≥30 kg/m2的非糖尿病成人内脏脂肪组织和异位脂肪的干预2或≥27公斤/米2和代谢综合征。参与者被随机分配接受每天一次皮下注射利拉鲁肽（目标剂量 3.0 mg）或匹配的安慰剂，为期 40 周。在基线和 40 周随访时通过磁共振成像评估身体脂肪分布和肌肉成分。肌肉成分通过大腿肌肉脂肪和肌肉体积的组合来描述。治疗差异（95% 置信区间 [CI]）通过针对基线大腿肌肉脂肪进行调整的最小二乘法计算。使用斯皮尔曼相关系数评估大腿肌肉脂肪变化与体重变化之间的关联。探讨了利拉鲁肽与安慰剂相比对不良肌肉成分（以高大腿肌肉脂肪和低大腿肌肉体积表示）的影响。 结果在 128 名接受影像随访的参与者中（92.2% 为女性，36.7% 黑人），基线时的中位肌肉脂肪为7.8%。在随机接受利拉鲁肽治疗的参与者中，中位随访 36 周期间大腿肌肉脂肪的平均百分比变化为 -2.87%（n= 73），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，磷‐值 0.009）。安慰剂组大腿肌肉脂肪的纵向变化与体重变化显着相关，但利拉鲁肽组则不然。在利拉鲁肽随访期间，肌肉成分不良的参与者比例从 11.0% 下降至 8.2%，但安慰剂组没有变化。结论在一组主要是超重或肥胖但没有糖尿病的女性队列中，每天一次皮下注射与安慰剂相比，利拉鲁肽可减少大腿肌肉脂肪和不良肌肉成分。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。