由于致病性杂合黑皮素4受体（MC4R）突变而导致肥胖的个体可以用胰高血糖素样肽-1受体激动剂（GLP-1RA）利拉鲁肽有效治疗。这里,我们报告了利拉鲁肽3mg/天治疗16周的效果,该患者因纯合致病性MC4R突变而患有病态肥胖和2型糖尿病(T2D).体重减轻了9.7公斤，与杂合MC4R突变携带者和常见肥胖的体重减轻相似。此外,治疗导致临床相关的空腹血糖下降，甘油三酯，收缩压,和葡萄糖耐量正常化。我们得出的结论是，利拉鲁肽可降低杂合和纯合MC4R突变携带者的体重和血糖水平。这作为概念证明,MC4R对于GLP-1RA的体重和葡萄糖降低作用不是必需的,并且利拉鲁肽可以用作由于MC4R突变而治疗肥胖症和T2D的一部分。
Individuals with obesity due to pathogenic heterozygous melanocortin 4 receptor (MC4R) mutations can be treated efficiently with the glucagon-like peptide-1 receptor agonist (GLP-1 RA) liraglutide. Here, we report the effect of 16 weeks of liraglutide 3 mg/day treatment in a woman with morbid obesity and type 2 diabetes (T2D) due to homozygous pathogenic MC4R mutation. The body weight loss was 9.7 kg, similar to weight loss in heterozygous MC4R mutation carriers and common obesity. In addition, the treatment led to clinically relevant decreases in fasting glucose, triglycerides, systolic blood pressure, and normalization of glucose tolerance. We conclude that liraglutide reduces body weight and blood glucose levels in hetero- and homozygous MC4R mutation carriers. This serves as proof-of-concept that MC4Rs are not required for the body weight and glucose lowering effects of GLP-1 RAs and that liraglutide may be used as part of the treatment of obesity and T2D due to MC4R mutations.
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