Genetic variation in GLP1 receptor is associated with interindividual differences in weight lowering potential of liraglutide in obese women with PCOS

Pharmacogenomics of GLP-1 receptor agonists: a genome-wide analysis of observational data and large randomised controlled trials

“…36 In a pilot study involving women with obesity with polycystic ovary syndrome, the Pro7Leu has also been associated with weight lowering potential of liraglutide. 8 The frequency of the minor allele in rs140226575G→A (Thr370Met), a variant that largely drives the ARRB1 signal, varies by ethnicity with a frequency of 0•05% in White Europeans, 6% in Hispanics, and 11% in American Indians or Alaska Natives, and is almost monomorphic in populations of African and Asian descent. However, the effect size for associations between rs140226575 and GLP1 receptor agonists response was similar across ethnicities, which will result in greater population effect of this variant on GLP1 receptor agonists response among Hispanics and American Indians or Alaska Natives.…”

“…Given the role of the GLP1R as the target for GLP1 receptor agonists, we examined two nonsynonymous variants in the GLP1R gene, rs6923761G→A (Gly168Ser) and rs10305420C→T (Pro7Leu), which have previously been reported to potentially alter response to GLP1 receptor agonists. [7][8][9][10] The two GLP1R singlenucleotide polymorphisms (SNPs) were extracted from the respective GWAS data of contributing cohorts from DIRECT, PRIBA, PROMASTER, HARMONY phase 3 and AWARD. Both SNPs were either directly genotyped or imputed with imputation score of more than 0•95 and HardyWeinberg Equilibrium p>0•05.…”

Combining SGLT2 inhibitor and GLP-1 agonist: exaggerated weight loss in a morbidly obese patient with type 2 diabetes

“…11 Our patient's heightened weight loss may be partly due to individual variation in response to either of the medications as a 'hyperresponder'. However, this patient's weight loss was maximised by the discontinuation of insulin.…”