AUTHOR=Wang Dong-Dong , Zhang Cun , Hu Ke , He Su-Mei , Zhu Ping , Chen Xiao 

TITLE=Therapeutic effect and rebound evaluation of dapagliflozin on glycated hemoglobin (HbA1c) in type 1 diabetes mellitus patients

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 13 - 2022

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.972878

DOI=10.3389/fphar.2022.972878

ISSN=1663-9812

ABSTRACT=Dapagliflozin has been used to treat patients with type 1 diabetes mellitus (T1DM), however the actual drug efficacy of dapagliflozin on glycated hemoglobin (HbA1c) and whether there is a rebound from dapagliflozin efficacy on HbA1c remain unknown. The present study aimed to explore the actual therapeutic effect and rebound situation of dapagliflozin on HbA1c in T1DM patients. Two 5 mg/day dapagliflozin dosage groups and three 10 mg/day dapagliflozin dosage groups, a total 1594 T1DM patients were collected for analysis with a non-linear mixed effect model. The change rate of HbA1c from baseline value was chosen as dapagliflozin pharmacodynamic evaluation index. After deducting control group effects, 5 and 10 mg/day dapagliflozin on HbA1c in T1DM were no significant difference. In addition, the actual maximal efficacy (AEmax) of dapagliflozin on HbA1c was -6.24% at week 9. When it reached the AEmax, the dapagliflozin pharmacodynamic rebound on HbA1c occurred, and continuing treatment for 0.5 and 1 years, the actual efficacies were -4.70% (75% AEmax) and -3.27% (52% AEmax), respectively. It was the first time to clarify the actual therapeutic effect and rebound situation of dapagliflozin on HbA1c in T1DM patients, providing reference value for clinical practice.