Endocrine Abstracts

Objective: The weight lowering potential of glucagon-like peptide (GLP) 1 receptor agonists (RAs) is interindividually different and clinically unpredictable. The potential role of genetic variability of GLP1R on body weight response to GLP1 RA has not yet been evaluated. The aim of the study was to assess the effect of common non-synonymous GLP1R single nucleotide polymorphisms (SNPs) rs6923761 and rs10305420 on weight loss in response to long acting GLP1 RA liraglutide in obese women with PCOS.

Methods: 59 obese women with PCOS (aged 30.7±6.9, BMI 38.4±5.3 kg/m²) were assigned to liraglutide 1.2 mg QD sc. for 12 weeks. They were genotyped for GLP1R rs6923761 and rs10305420. Changes of body mass, BMI, waist circumference and visceral adipose tissue (VAT) area were measured before and at the end of the study.

Results: After treatment intervention women lost on average 3.96±3.24 kg (P<0.001), BMI was reduced for 1.44±1.22 kg/m² (P<0.001), waist circumference for 3.31±4.13 cm (P<0.001) and VAT for 7.05±18.55 cm² (P=0.002). Twenty (34%) out of 59 subjects were good responders and lost 5% or more of their initial body weight. Carriers of at least one polymorphic rs10305420 allele had worse treatment response compared to carriers of two WT alleles (OR=0.27, 95% CI=0.09–0.85, P=0.025). Carriers of at least one polymorphic rs6923761 allele tended to have better treatment response compared to carriers of two WT alleles, but the difference was not statistically significant (OR=3.06, 95% CI=0.96–9.74, P=0.058).

Conclusion: Polymorphism of GLP1R rs10305420 accounts for interindividual differences in response to liraglutide regarding weight loss in obese women with PCOS. Future studies will determine whether such genetic variation may be clinically useful in prediction of the weight lowering potential of GLP1 RAs in obese individuals.