1.
Patients with Obesity Caused by Melanocortin-4 Receptor Mutations Can Be Treated with a Glucagon-like Peptide-1 Receptor Agonist.
Iepsen, EW, Zhang, J, Thomsen, HS, Hansen, EL, Hollensted, M, Madsbad, S, Hansen, T, Holst, JJ, Holm, JC, Torekov, SS
Cell metabolism. 2018;(1):23-32.e3
Abstract
Pathogenic mutations in the appetite-regulating melanocortin-4 receptor (MC4R) represent the most common cause of monogenic obesity with limited treatment options. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) cause weight loss by reducing appetite. We assessed the effect of the GLP-1 RA liraglutide 3.0 mg for 16 weeks in 14 obese individuals with pathogenic MC4R mutations (BMI 37.5 ± 6.8) and 28 matched control participants without MC4R mutation (BMI 36.8 ± 4.8). Liraglutide decreased body weight by 6.8 kg ± 1.8 kg in individuals with pathogenic MC4R mutations and by 6.1 kg ± 1.2 kg in control participants. Total body fat, waist circumference, and fasting and postprandial glucose concentrations similarly decreased in both groups. Thus, liraglutide induced an equal, clinically significant weight loss of 6% in both groups, indicating that the appetite-reducing effect of liraglutide is preserved in MC4R causal obesity and that liraglutide acts independently of the MC4R pathway. Thus, liraglutide could be an effective treatment of the most common form of monogenic obesity.
2.
Evaluation of weight loss and metabolic changes in diabetic patients treated with liraglutide, effect of RS 6923761 gene variant of glucagon-like peptide 1 receptor.
de Luis, DA, Diaz Soto, G, Izaola, O, Romero, E
Journal of diabetes and its complications. 2015;(4):595-8
Abstract
BACKGROUND A polymorphism of GLP-1 R (rs6923761) has potential implications in weight loss and metabolic control. We decide to investigate the role of this polymorphism on metabolic changes and weight loss secondary to treatment with liraglutide. MATERIAL AND METHODS A population of 90 patients with diabetes mellitus type 2 and overweight, unable to achieve glycemic control (HbA1c>7%) with metformin alone that require initiation of liraglutide treatment in progressive dose to 1.8mg/day subcutaneously, was analyzed. RESULTS Fifty one patients (56.7%) had the genotype GG and 39 (43.3%) patients; GA (30 patients, 33.3%) or AA (9 patients, 10%) (A allele carriers). In patients with both genotypes, body mass index (BMI), weight and fat decreased. The proportion of the mentioned reductions was higher in the variant allele carriers; BMI (-0.59±2.5kg/m(2) vs. -1.69±3.9kg/m(2); P<0.05), weight (-2.78±2.8kg vs. -4.52±4.6kg; P<0.05) and fat mass (-0.59±2.5kg vs. -1.69±3.9kg; P<0.05). Weight reduction after liraglutide treatment was greater in the A-allele carriers by 2.9kg (95% CI: 0.27-5.64). The decrease of basal glucose, HOMA-R and HbA1c was similar in both genotypes. CONCLUSION Our data showed better anthropometric parameters in overweight diabetic subjects with the variant allele (A) of rs6923761 GLP-1 R polymorphism. A allele carriers had a greater decrease in weight and fat mass after treatment with liraglutide. The present study is a preliminary observation, and its results need to be replicated with a higher number of patients in different populations.