Department of Phase I Clinical Trial Unit, The First Hospital of Jilin University, Changchun, Jilin, China.
Shenzhen Salubris Pharmaceuticals Co Ltd, Shenzhen, Guangdong China.
Expert Opin Drug Metab Toxicol. 2021 Jun;17(6):725-731. doi: 10.1080/17425255.2021.1915283. Epub 2021 Apr 26.
Dipeptidyl peptidase-4 (DPP-4) inhibitors have significant clinical efficacy for type 2 diabetes mellitus (T2DM). The combination of fotagliptin (FOT) with metformin (MET) is a promising therapeutic approach in MET-resistant patients. The aim of the present study was to evaluate the pharmacokinetic (PK) interaction between FOT and MET in healthy subjects after multiple-dose administration.
Eighteen participants received a randomized open-label, three period treatment that included MET 1000 mg alone, co-administration of FOT 24 mg and MET, followed by FOT 24 mg alone. Serial blood samples were collected for PK analysis, which included geometric mean ratios (GMRs) with 90% confidence intervals (CIs), area under the concentration-time curve (AUC), and maximum plasma concentration (C).
Analysis results showed that for FOT alone or combination therapy, the 90% CIs of the for AUC and C were 102.08% (98.9%, 105.36%) and 110.65% (102.19%, 119.82%), respectively. For MET, they were 113.41% (100.32%, 128.22%) and 97.11% (83.80%, 112.55%) for AUC and C, respectively. FOT or MET monotherapy and the combination therapy with both drugs were well tolerated.
No PK drug-drug interactions were found in the combination therapy with FOT and MET. Therefore, FOT can be co-administered with MET without dose adjustment.
The trial is registered at http://www.chinadrugtrials.org.cn/(Registration No. CTR20190221).
二肽基肽酶-4（DPP-4）抑制剂对 2 型糖尿病（T2DM）具有显著的临床疗效。在二甲双胍（MET）耐药患者中，将伏格列波糖（FOT）与 MET 联合使用是一种很有前途的治疗方法。本研究旨在评估健康受试者多次给药后 FOT 与 MET 之间的药代动力学（PK）相互作用。
18 名参与者接受了一项随机、开放标签、三周期治疗，包括单独服用 MET 1000mg、联合服用 FOT 24mg 和 MET，然后单独服用 FOT 24mg。连续采集血样进行 PK 分析，包括几何均数比值（GMR）及其 90%置信区间（CI）、药时曲线下面积（AUC）和最大血浆浓度（C）。
分析结果表明，对于 FOT 单独或联合治疗，AUC 和 C 的 90%CI 分别为 102.08%（98.9%，105.36%）和 110.65%（102.19%，119.82%）。对于 MET，AUC 和 C 的 90%CI 分别为 113.41%（100.32%，128.22%）和 97.11%（83.80%，112.55%）。FOT 或 MET 单药治疗和联合两种药物治疗均耐受良好。
FOT 与 MET 联合治疗未发现 PK 药物相互作用。因此，无需调整剂量即可联合使用 FOT 和 MET。
该试验在中国临床试验注册中心注册（注册号：CTR20190221）。
