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=13

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=<p>Dapagliflozin has been used to treat patients with type 1 diabetes mellitus; 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 type 1 diabetes mellitus patients. A total of 1,594 type 1 diabetes mellitus patients were enrolled for analysis using a non-linear mixed effect model from randomized controlled trials from published literature works including two 5 mg/day dapagliflozin dosage groups and three 10 mg/day dapagliflozin dosage groups. The change rate of HbA1c from a baseline value was chosen as a dapagliflozin pharmacodynamic evaluation index. After deducting control group effects, the therapeutic effect of 5 and 10 mg/day dapagliflozin on HbA1c in type 1 diabetes mellitus patients had no significant difference. In addition, the actual maximal efficacy (AE<sub>max</sub>) of dapagliflozin on HbA1c was -6.24% at week 9. When it reached the AE<sub>max</sub>, the dapagliflozin pharmacodynamic rebound on HbA1c occurred, and when the treatment was continued for 0.5 and 1 year, the actual efficacies were -4.70% (75% AE<sub>max</sub>) and -3.27% (52% AE<sub>max</sub>), respectively. This was the first time to clarify the actual therapeutic effect and rebound situation of dapagliflozin on HbA1c in type 1 diabetes mellitus patients, providing a reference value for clinical practices.</p>