Weight loss from glucagon-like peptide-1 receptor agonists by genetic factors in adults with type 2 diabetes

Le résumé fourni par la source

AIMS: To identify whether genetic predisposition to obesity influences the weight loss effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) among adults with type 2 diabetes (T2D). METHODS: This study evaluated 52-week weight loss trajectories. Genetic exposures comprised: 1) a BMI polygenic risk score (PRS) incorporating 935,416 single-nucleotide polymorphisms (SNPs) and stratified into low (bottom 20 %), intermediate (middle 60 %), and high (top 20 %) categories; and 2) five major genetic variants for BMI PRS. Linear mixed models were applied to assess the associations between genetic factors and weight loss percentage, and the interaction effect between genetic factors and follow-up time was further considered. RESULTS: Among the 1,055 included adults (mean age 59 ± 11 years, 55 % female), intermediate and high BMI PRS groups were modestly associated with less weight loss over 52 weeks (0.7 % and 1.5 %, P = 0.0017 and 0.0023, respectively) than the low BMI PRS group. Individual SNPs showed no significant association with weight loss. BMI PRS modified response over time-intermediate PRS showed less early weight loss, whereas high PRS showed less late weight loss; several genotypes also showed significant time-varying effects. CONCLUSIONS: BMI PRS could potentially be used to personalize obesity management with GLP-1RAs. Large-scale, multi-ancestry studies are needed to validate the application.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.