Toomata Zanetta L L, Jiang Yannan, Yeu Rui Qian, Brandon Rebecca, Tweedie-Cullen Ry Yves, Nehren Norma, Doherty Glenn, Watson Huti, Macaskill-Smith Kerry A, Leask Megan, Merriman Tony R, Paul Ryan, Merry Troy L, Shepherd Peter R, Murphy Rinki
Department of Medicine, Faculty of Medical and Health Sciences, the University of Auckland, Auckland, New Zealand.
Maurice Wilkins Centre for Molecular Biodiscovery, the University of Auckland, Auckland, New Zealand.
Diabetes Metab Syndr Obes. 2025 Apr 23;18:1255-1262. doi: 10.2147/DMSO.S500336. eCollection 2025.
BACKGROUND/OBJECTIVES: This subgroup analysis of a randomised, open-label, two-period crossover trial in Aotearoa New Zealand (February 2019 to March 2020) assessed whether the glucose-lowering effects of vildagliptin, vs pioglitazone varied by the (p.Arg457Gln) rs373863828 genotype.
Adults with type 2 diabetes and HbA1c > 58 mmol/mol (>7.5%) received either pioglitazone (30 mg) or vildagliptin (50 mg) for 16 weeks, then switched medications for another 16 weeks. Differences in HbA1c between treatments (pioglitazone vs vildagliptin) were tested for an interaction with rs373863828 A-allele carrier status and controlling for baseline HbA1c using linear mixed models. Secondary endpoints included weight, systolic blood pressure, and diabetes treatment satisfaction.
Participants with the AA/AG genotype had a higher baseline weight than those with the GG genotype (121.4 kg vs 106.6 kg, respectively; <0.01). No significant difference in achieved HbA1c was found based on A-allele carrier status (0.43 mmol/mol; 95% CI -4.83, 5.69; =0.87). Among Māori and Pacific participants with the A-allele, a smaller weight difference was observed after pioglitazone vs vildagliptin compared to those with the GG genotype (interaction effect -1.66 kg; 95% CI -3.27, -0.05; =0.04).
rs373863828 A-allele carriers show a similar HbA1c-lowering response to pioglitazone vs vildagliptin compared to non-carriers but exhibit less weight gain with pioglitazone, despite having significantly higher baseline weights.
背景/目的：这项对新西兰（2019年2月至2020年3月）一项随机、开放标签、两期交叉试验的亚组分析评估了维格列汀与吡格列酮相比，其降糖效果是否因（p.Arg457Gln）rs373863828基因型而异。
2型糖尿病且糖化血红蛋白>58 mmol/mol（>7.5%）的成年人接受吡格列酮（30 mg）或维格列汀（50 mg）治疗16周，然后换药再治疗16周。使用线性混合模型测试治疗组（吡格列酮与维格列汀）之间糖化血红蛋白的差异与rs373863828 A等位基因携带者状态的相互作用，并控制基线糖化血红蛋白。次要终点包括体重、收缩压和糖尿病治疗满意度。
AA/AG基因型的参与者基线体重高于GG基因型的参与者（分别为121.4 kg和106.6 kg；<0.01）。基于A等位基因携带者状态，糖化血红蛋白的降低无显著差异（0.43 mmol/mol；95%CI -4.83，5.69；=0.87）。在携带A等位基因的毛利人和太平洋岛民参与者中，与GG基因型参与者相比，吡格列酮治疗后的体重差异小于维格列汀治疗后的体重差异（交互作用-1.66 kg；95%CI -3.27，-0.05；=0.04）。
与非携带者相比，rs373863828 A等位基因携带者对吡格列酮和维格列汀的糖化血红蛋白降低反应相似，但尽管基线体重显著较高，但服用吡格列酮后体重增加较少。
