Retrospective analysis of the effect of SGLT-2 inhibitors on renal function in patients with type 2 diabetes in the real world.

Introduction: The protective effect of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on the kidneys has been widely recognized. However, limited research has reported the changes in estimated glomerular filtration rate (eGFR) of real-world patients with type 2 diabetes mellitus (T2DM) over time after administration of SGLT-2 inhibitors. This study aimed to reflect the trend of eGFR changes over time in T2DM patients having different baseline eGFR after SGLT-2 inhibitors administration in the real world. Methods: A single-center retrospective study was performed in a tertiary public hospital in Beijing, China. In total, 998 outpatients with T2DM who initiated SGLT-2 inhibitors treatment were included in the study. The changes in eGFR, urinary albumin/creatinine ratio (UACR), and glycolipid metabolism indicators were analyzed during the 18-month follow-up period. Results: The eGFR levels significantly decreased to their lowest point (-3.04 mL/min/1.73 m2) in the first 3 months after initiation of SGLT-2 inhibitors treatment, however, gradually returned to the baseline level after 1 year. Compared to the subgroup with eGFR >90 mL/min/1.73 m2, improvements in renal function were more significant in patients with T2DM from the 60 < eGFR ≤90 mL/min/1.73 m2 and eGFR ≤60 mL/min/1.73 m2 subgroups after treatment with SGLT-2 inhibitors. Similarly, SGLT-2 inhibitors reduced the UACR in patients with diabetic nephropathy. Conclusion: This study further confirmed the real-world long-term protective effect of SGLT-2 inhibitors on the kidneys of patients with T2DM, which is not related to baseline renal function and blood glucose.

Effects of ginkgo leaf tablet on the pharmacokinetics of rosiglitazone in rats and its potential mechanism.

CONTEXT: Ginkgo leaf tablet (GLT), a traditional Chinese herbal formula, is often combined with rosiglitazone (ROS) for type 2 diabetes mellitus treatment. However, the drug-drug interaction between GLT and ROS remains unknown. OBJECTIVE: To investigate the effects of GLT on the pharmacokinetics of ROS and its potential mechanism. MATERIALS AND METHODS: The pharmacokinetics of 10 mg/kg ROS with 100/200 mg/kg GLT as single-dose and 10-day multiple-dose administration were investigated in Sprague-Dawley rats. In vitro, the effects of GLT on the activity of CYP2C8 and CYP2C9 were determined in recombinant human yeast microsomes and rat liver microsomes with probe substrates. RESULTS: The t1/2 of ROS increased from 2.14 ± 0.38 (control) to 2.79 ± 0.37 (100 mg/kg) and 3.26 ± 1.08 h (200 mg/kg) in the single-dose GLT administration. The AUC0-t (139.69 ± 45.46 vs. 84.58 ± 39.87 vs. 66.60 ± 15.90 h·µg/mL) and t1/2 (2.75 ± 0.70 vs. 1.99 ± 0.44 vs. 1.68 ± 0.35 h) decreased significantly after multiple-dose GLT treatment. The IC50 values of quercetin, kaempferol, and isorhamnetin, GLT main constituents, were 9.32, 7.67, and 11.90 µmol/L for CYP2C8, and 27.31, 7.57, and 4.59 µmol/L for CYP2C9. The multiple-dose GLT increased rat CYP2C8 activity by 44% and 88%, respectively. DISCUSSION AND CONCLUSIONS: The metabolism of ROS is attenuated in the single dose of GLT by inhibiting CYP2C8 and CYP2C9 activity, and accelerated after the multiple-dose GLT treatment via inducing CYP2C8 activity in rats, indicating that the clinical dose of ROS should be adjusted when co-administrated with GLT.

Effects of the total flavonoid extracts and the monomers of Daphne genkwa on CYP2C8 activity.

This study aimed to assess the effects of total flavonoid extracts (TFDG) and the monomers of Daphne genkwa on the CYP2C8 activity in vitro and in vivo.The 50% inhibitory concentration (IC50) values were used to determine the inhibitory effect of TFDG and its four monomers for the CYP2C8 activity by recombinant human CYP2C8 (RHCYP2C8) yeast microsome system in vitro, and the volume per dose index (VDI) was predicted the potential inhibition in vivo. The effects of multiple-dose administration of TFDG on the pharmacokinetic parameters of rosiglitazone in rats were evaluated.The IC50 values of apigenin, luteolin, hydroxy-genkwanin, genkwanin, and TFDG were 7.27 µmol/L, 11.9 µmol/L, 28.1 µmol/L, 127 µmol/L, and 13.4 µg/mL, respectively. The VDI values of apigenin and TFDG were 2.15 L and 6.60 L. In vivo study, compared with the control group, the elimination phase half-life and mean residence time in the TFDG treatment group were significantly increased by 96.9% and 106.8% (p <.05), respectively.Apigenin showed a moderate inhibitory effect on the CYP2C8 activity in vitro, while the other three monomers were weak inhibitors. TFDG had a strong inhibitory effect on CYP2C8 in vitro and in vivo, and also inhibited the metabolism of rosiglitazone in rats.