アメリカ糖尿病学会2020の発表です。遺伝子型は、the role of rs7202877 (T>G) polymorphism in CTRB1/2 gene という型です。
935-P — 2020 ADA Effect of CTRB1/2 RS7202877 (T>G) Polymorphism on Weight Loss Response to Liraglutide Treatment in Greek People with Type 2 Diabetes
Previous studies have demonstrated an association between gene polymorphisms and weight loss response to GLP-1 RA therapy. We aimed to evaluate the role of rs7202877 (T>G) polymorphism in CTRB1/2 gene in weight loss response to liraglutide among Greek people with T2D. 116 adults with T2D (51% female, mean BMI 35.4±6.4 kg/m2, mean age 68.3±10.9 years), who had been on treatment with liraglutide for at least 6 months were genotyped for the rs7202877 polymorphism, using real-time PCR. Responders were defined as subjects who lost 3% or more of their baseline weight, whereas non-responders those who lost less than 3% of their initial weight after 3 or 6 months of liraglutide administration. 77 (66%) individuals were classified as responders and 39 (34%) as non-responders. 97 (84%) patients were homozygous for the wild type rs7202877 T allele (TT) and 19 (16%) patients carried one polymorphic G allele (TG). The probability of being weight loss responder was increased by 12%, when carrying the G allele; however, the result did not achieve significance (OR:1.12, 95% 0.4, 3.2, P=0.84). In the response group, weight was reduced by 5.9 kg (95% CI: -6.9, -4.9, P<0.0001) and by 6.4 kg (95% CI: -8, -4.9, P<0.0001) from baseline to 3 and 6 months, respectively. More non-responders were treated with a combination of oral agents and insulin at baseline, compared to responders (OR: 0.25, 95% CI: 0.07, 0.84, P=0.008). Both responders and non-responders exhibited a reduction in HbA1c during the study (-0.9%, P<0.0001 and -0.5%, P=0.008, respectively). The probability of being a weight loss responder was decreased by 26% for every 10 kg increase in baseline weight (adjusted for baseline HbA1c OR: 0.97, 95% CI: 0.95, 0.99, P=0.027). Our findings do not suggest a role of CTRB1/2rs7202877 polymorphism in affecting weight loss response to liraglutide in Greek people with T2D. In contrast, lower baseline body weight might be related to better weight control following treatment with liraglutide.