1.
Pharmacokinetics and Pharmacodynamics of Henagliflozin, a Sodium Glucose Co-Transporter 2 Inhibitor, in Chinese Patients with Type 2 Diabetes Mellitus.
Yong, X, Wen, A, Liu, X, Liu, H, Liu, YP, Li, N, Hu, T, Chen, Y, Wang, M, Wang, L, et al
Clinical drug investigation. 2016;(3):195-202
Abstract
BACKGROUND AND OBJECTIVE Henagliflozin, a selective inhibitor of the renal sodium glucose cotransporter-2, was developed for type 2 diabetes mellitus (T2DM). This study characterized single- and multiple-dose pharmacokinetics and pharmacodynamics of henagliflozin in Chinese patients with T2DM. METHODS Thirty T2DM patients were randomized in a 4:1 ratio to orally receive either henagliflozin 5, 10, 20 mg/day or placebo for 10 days, except on day 2 and day 3. Pharmacokinetic and pharmacodynamic profiles were measured on day 1 and day 10. RESULTS Henagliflozin exhibited dose-proportional plasma concentrations with a half-life ranging from 9.1 to 14 h. Steady-state plasma henagliflozin concentration was reached by day 7 in all active treatment groups. Henagliflozin decreased the 24-h mean plasma glucose by -0.3, -1.0 and -1.0 mmol/L with doses of 5, 10 and 20 mg on day 1, respectively. The corresponding values on day 10 were -0.8, -0.9 and -1.2 mmol/L. Twenty-four-hour urinary glucose excretion increased by 11, 65 and 82 times with doses of 5, 10 and 20 mg on day 1, respectively, with a similar trend on day 10. No treatment-related serious adverse events or discontinuations due to adverse events occurred. CONCLUSIONS The observed pharmacokinetic and pharmacodynamic profiles of henagliflozin support a once-daily dosing regimen in Chinese T2DM patients.
2.
Exploring causal associations of alcohol with cardiovascular and metabolic risk factors in a Chinese population using Mendelian randomization analysis.
Taylor, AE, Lu, F, Carslake, D, Hu, Z, Qian, Y, Liu, S, Chen, J, Shen, H, Smith, GD
Scientific reports. 2015;:14005
Abstract
Observational studies suggest that moderate alcohol consumption may be protective for cardiovascular disease, but results may be biased by confounding and reverse causality. Mendelian randomization, which uses genetic variants as proxies for exposures, can minimise these biases and therefore strengthen causal inference. Using a genetic variant in the ALDH2 gene associated with alcohol consumption, rs671, we performed a Mendelian randomization analysis in 1,712 diabetes cases and 2,076 controls from Nantong, China. Analyses were performed using linear and logistic regression, stratified by sex and diabetes status. The A allele of rs671 was strongly associated with reduced odds of being an alcohol drinker in all groups, but prevalence of alcohol consumption amongst females was very low. The A allele was associated with reduced systolic and diastolic blood pressure and decreased total and HDL cholesterol in males. The A allele was also associated with decreased triglyceride levels, but only robustly in diabetic males. There was no strong evidence for associations between rs671 and any outcomes in females. Our results suggest that associations of alcohol consumption with blood pressure and HDL-cholesterol are causal. Alcohol also appeared to have adverse effects on triglyceride levels, although this may be restricted to diabetics.