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Role of Genetic Variation in the Cannabinoid Receptor Gene (CNR1) (G1359A Polymorphism) on Weight Loss and Cardiovascular Risk Factors After Liraglutide Treatment in Obese Patients With Diabetes Mellitus Type 2
  1. Daniel Antonio de Luis, MD,
  2. Hilda F. Ovalle, PhD,
  3. Gonzalo Diaz Soto, PhD,
  4. Olatz Izaola, PhD,
  5. Beatriz de la Fuente, PhD,
  6. Enrique Romero, MD
  1. From the Center of Investigation of endocrinology and Nutrition, Medicine School and Unit of Investigation, Hospital Rio Hortega, University of Valladolid, Valladolid, Spain.
  1. Received May 20, 2013, and in revised form October 4, 2013.
  2. Accepted for publication October 22, 2013.
  3. Reprints: Daniel Antonio de Luis, MD, Center of Investigation of Endocrinology and Nutrition, Medicine School, Valladolid University, C/Los perales 16, Simancas 47130, Valladolid, Spain. E-mail: dadluis{at}
  4. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
  5. The author report no conflicts of interest.
  6. Authors’ contributions: D.A.dL. and G.D.S.: designed the study and wrote the article; H.F.O.: laboratory determinations; O.I., E.R., and B.F.: anthropometric and dietetic works.


Background A polymorphism (1359 G/A) of the cannabinoid receptor 1 (CNR1) gene was reported as a common polymorphism (rs1049353) with potential implications in weight loss. We decide to investigate the role of this polymorphism on metabolic changes and weight loss secondary to treatment with liraglutide.

Methods A population of 86 patients with diabetes mellitus type 2 and obesity, unable to achieve glycemic control (hemoglobine glycate A1c >7%) with metformin alone or associated to sulfonylurea, who require initiation of liraglutide treatment in progressive dose to 1.8 mg/d subcutaneously, was analyzed.

Results Fifty-one patients (59.3%) had the genotype G1359G, and 35 patients (40.7%) had G1359A (28 patients, 32.6%) or A1359A (7 patients, 8.1%) (A allele carriers). In patients with both genotypes, basal glucose, HbA1c, body mass index, weight, fat mass, waist circumference, and systolic blood pressures decreased. In patients with G1359G genotype, total cholesterol and low-density lipoprotein cholesterol decreased, and in patients with A allele, homeostasis model assessment for insulin resistance decreased, too.

Conclusions There is an association of the A allele with an improvement of insulin resistance secondary to weight loss after liraglutide treatment in obese patients with diabetes mellitus type 2. Noncarriers of A allele showed an improvement in cholesterol levels after weight loss.

Key Words
  • cannabinoid receptor gene
  • liraglutide
  • metabolic parameters
  • obesity

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