Improvement of insulin sensitivity in T2DM patients by glucagon-like peptide fusion protein
10.12092/j.issn.1009-2501.2024.08.005
- VernacularTitle:促胰岛素分泌肽融合蛋白对T2DM患者胰岛素敏感性改善研究
- Author:
Huan LIU
1
;
Yang LIU
;
Dan LUO
;
Lixin GUO
;
Dongyang LIU
Author Information
1. 北京大学第三医院药物临床试验机构,北京 100191
- Keywords:
E4F4;
population oral glucose mini-mal model;
insulin sensitivity
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2024;29(8):879-886
- CountryChina
- Language:Chinese
-
Abstract:
AIM:In order to quantitatively exam-ine the improvement of insulin sensitivity(IS)in pa-tients with type 2 diabetes mellitus(T2DM)when exendin-4-lgG4-Fc(E4F4)was given for 12 weeks,the present study was conducted to establish E4F4 population oral glucose minimal models based on the meal tolerance test(MTT)data of E4F4 pre-and post-dosing,and to analyze whether low-dose(2.7 mg)administration for 12 weeks significantly improved insulin sensitivity in patients with T2DM.METHODS:Blood glucose and insulin concentra-tions were collected among 16 subjects in the study who completed MTT before or after dosing.Nonlinear mixed-effects model construction for the population oral glucose minimal models was per-formed using NONMEN 7.2 software using pre-and post-dosing data,respectively.The insulin sensitivi-ty parameters obtained from the models before and after the administration of the drug were sta-tistically analyzed using GraphPad Prism 8.0.RE-SULTS:Nonparametric test of IS before and after dosing showed statistical difference(P=0.02),and insulin sensitivity after dosing was significantly higher than the baseline value before dosing.CON-CLUSION:12 weeks of low-dose E4F4 treatment in patients with type 2 diabetes mellitus resulted in an improvement in insulin sensitivity.This study provides a pharmacodynamic basis for the efficacy of this novel biologic.
