The glucagon-like peptide-1 analog liraglutide suppresses ghrelin and controls diabetes in a patient with Prader-Willi syndrome

Abstract

Prader-Willi syndrome (PWS) is a genetic disease characterized by severe morbid obesity in association with hyperphagia and type 2 diabetes mellitus. Liraglutide is a glucagon-like peptide (GLP)-1 analog that controls appetite, decreases body weight and improves glycemic control. However, it is unclear if PWS patients with diabetes experience similar benefits of liraglutide therapy. In a 25 year-old female hyperglycemic PWS patient, liraglutide monotherapy improved her Hemoglobin A1c remarkably (12.6% to 6.1%) while steadily decreasing her body mass index (BMI: 39.1 kg/m² to 35.7 kg/m²). We offered this patient continued liraglutide therapy for one year to determine the effect on various metabolic parameters. Her hyperphagia was controlled soon after liraglutide treatment commenced and remained so throughout the treatment. The metabolic parameters changed as follows: visceral fat area fell from 150.1 to 113.2 (cm²); plasma insulin rose from 108.1 to 277.0 (pmol/L); plasma active GLP-1 dropped from 2.1 to 1.2 (fmol/L); plasma active ghrelin diminished from 137.0 to 27.7 (pmol/L). While plasma active ghrelin before treatment was abnormally high, even though her GLP-1 was normal, both decreased following liraglutide therapy. These results suggest that in addition to its insulinotropic effects, other potential mechanisms activated by liraglutide therapy may reduce the plasma ghrelin levels elevated in PWS, leading to an improvement in overeating, BMI and visceral fat, as well as glycemic control.