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

J Diabetes Complications. 2015 May-Jun;29(4):595-8. doi: 10.1016/j.jdiacomp.2015.02.010. Epub 2015 Feb 25.

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.

Keywords: Glucagon-like peptide 1 receptor; Liraglutide; Metabolic parameters; Obesity; rs6923761.

Publication types

  • Controlled Clinical Trial

MeSH terms

  • Aged
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism
  • Female
  • Glucagon-Like Peptide-1 Receptor / genetics*
  • Glycated Hemoglobin / metabolism
  • Humans
  • Liraglutide / administration & dosage
  • Liraglutide / therapeutic use*
  • Male
  • Metformin / administration & dosage
  • Middle Aged
  • Obesity / complications
  • Obesity / drug therapy
  • Obesity / genetics
  • Obesity / metabolism
  • Overweight / complications
  • Overweight / drug therapy*
  • Overweight / genetics
  • Overweight / metabolism
  • Polymorphism, Single Nucleotide*
  • Weight Loss / drug effects*
  • Weight Loss / genetics

Substances

  • Blood Glucose
  • Glucagon-Like Peptide-1 Receptor
  • Glycated Hemoglobin A
  • hemoglobin A1c protein, human
  • Liraglutide
  • Metformin