A <scp><i>GLP1R</i></scp> gene variant and sex influence the response to semaglutide treatment in patients with severe obesity
Aurélie Phan, Claire Carette, Céline Narjoz, Claire Rives‐Lange, Nathalie Rassy, Sébastien Czernichow, Nicolas Pallet
Abstract
OBJECTIVE: The objective of this study is to identify whether the glucagon-like peptide-1 receptor (GLP1R) gene variant rs6923761G→A has an influence on semaglutide response in individuals with severe obesity. METHODS: ). RESULTS: The frequency of the rs6923761 AA variant was 9 out of 112 patients (8%), GA was 42 out of 112 (37.5%), and GG was 61 out of 112 (54.5%). The mean weight loss kinetics was 1.64% (SD 0.78%) per month in homozygotes of variant A in comparison with a mean weight loss of 1.04% (SD 0.79%) per month in carriers of at least one G variant (p = 0.03). Multivariate analysis demonstrated that rs6923761G→A and sex were independent predictors of weight loss. The rate of weight loss in women homozygous for the A allele was more than double that observed in men carrying the G allele: mean (SD) 1.89% (0.75%) per month versus 0.7% (0.7%) per month (p = 0.0009). No woman homozygous for the A allele was a nonresponder, compared with 56% (21 out of 37) of the men carrying the G allele. CONCLUSIONS: The rs6923761G→A gene variant and sex profoundly affect weight loss in response to semaglutide in patients with severe obesity.