1.
Dorzagliatin monotherapy in Chinese patients with type 2 diabetes: a dose-ranging, randomised, double-blind, placebo-controlled, phase 2 study.
Zhu, D, Gan, S, Liu, Y, Ma, J, Dong, X, Song, W, Zeng, J, Wang, G, Zhao, W, Zhang, Q, et al
The lancet. Diabetes & endocrinology. 2018;(8):627-636
Abstract
BACKGROUND Glucokinase acts as a glucose sensor in the pancreas and a glucose processor in the liver, and has a central role in glucose homoeostasis. Dorzagliatin is a new, dual-acting, allosteric glucokinase activator that targets both pancreatic and hepatic glucokinases. Dorzagliatin has good pharmacokinetic and pharmacodynamic properties in humans, and provides effective 24-h glycaemic control and improves glucose sensitivity in patients with type 2 diabetes. We aimed to assess the efficacy and safety of dorzagliatin monotherapy at different doses in Chinese patients with type 2 diabetes. METHODS In this multicentre, randomised, double-blind, placebo-controlled, phase 2 study, we randomly assigned (1:1:1:1:1) patients to receive oral placebo or one of four doses of oral dorzagliatin (75 mg once a day, 100 mg once a day, 50 mg twice a day, or 75 mg twice a day) using permuted-block randomisation, with a block size of ten and without stratification. Eligible patients were men or non-fertile women (aged 40-75 years) with type 2 diabetes who had a BMI of 19·0-30·0 kg/m2, were on a diet and exercise regimen, and were previously untreated or treated with metformin or α-glucosidase inhibitor monotherapy. The study started with a 4-week placebo run-in period followed by a 12-week treatment period. The primary endpoint was the change in HbA1c from baseline to week 12, which was assessed in all patients who received at least one dose of study drug and had both baseline and at least one post-baseline HbA1c value. Safety was assessed in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT02561338. FINDINGS Between Sept 29, 2015, and Aug 17, 2016, we randomly assigned 258 patients to one of the five study groups. At the end of 12 weeks, the least squares mean change in HbA1c from baseline was -0·35% (95% CI -0·60 to -0·10) in the placebo group, -0·39% (-0·64 to -0·14) in the 75 mg once daily group, -0·65% (-0·92 to -0·38) in the 100 mg once daily group, -0·79% (-1·06 to -0·52) in the 50 mg twice daily group, and -1·12% (-1·39 to -0·86) in the 75 mg twice daily group. Compared with the placebo group, the change in HbA1c between baseline and 12 weeks was significant in the 50 mg twice daily (p=0·0104) and the 75 mg twice daily (p<0·0001) groups. The number of adverse events was similar between the treatment groups and the placebo group. There were no reports of drug-related serious adverse events or severe hypoglycaemia. INTERPRETATION Dorzagliatin had a beneficial effect on glycaemic control and was safe and well tolerated over 12 weeks in Chinese patients with type 2 diabetes. FUNDING Hua Medicine, National Major Scientific and Technological Special Project for Significant New Drugs Development, Shanghai Science and Technology Innovation Action Project, Shanghai Pudong District Science and Technology Innovation Action Project, and Shanghai Municipal Commission of Economy and Informatisation Innovation Action Project.
2.
Arterial Effects of Canakinumab in Patients With Atherosclerosis and Type 2 Diabetes or Glucose Intolerance.
Choudhury, RP, Birks, JS, Mani, V, Biasiolli, L, Robson, MD, L'Allier, PL, Gingras, MA, Alie, N, McLaughlin, MA, Basson, CT, et al
Journal of the American College of Cardiology. 2016;(16):1769-1780
Abstract
BACKGROUND Evidence suggests that interleukin (IL)-1β is important in the pathogenesis of atherosclerosis and its complications and that inhibiting IL-1β may favorably affect vascular disease progression. OBJECTIVES The goal of this study was to evaluate the effects of IL-1β inhibition with canakinumab versus placebo on arterial structure and function, determined by magnetic resonance imaging. METHODS Patients (N = 189) with atherosclerotic disease and either type 2 diabetes mellitus or impaired glucose tolerance were randomized to receive placebo (n = 94) or canakinumab 150 mg monthly (n = 95) for 12 months. They underwent magnetic resonance imaging of the carotid arteries and aorta. RESULTS There were no statistically significant differences between canakinumab compared with placebo in the primary efficacy and safety endpoints. There was no statistically significant change in mean carotid wall area and no effect on aortic distensibility, measured at 3 separate anatomic sites. The change in mean carotid artery wall area was -3.37 mm2 after 12 months with canakinumab versus placebo. High-sensitivity C-reactive protein was significantly reduced by canakinumab compared with placebo at 3 months (geometric mean ratio [GMR]: 0.568; 95% confidence interval [CI]: 0.436 to 0.740; p < 0.0001) and 12 months (GMR: 0.56; 95% CI: 0.414 to 0.758; p = 0.0002). Lipoprotein(a) levels were reduced by canakinumab compared with placebo (-4.30 mg/dl [range: -8.5 to -0.55 mg/dl]; p = 0.025] at 12 months), but triglyceride levels increased (GMR: 1.20; 95% CI: 1.046 to 1.380; p = 0.01). In these patients with type 2 diabetes mellitus or impaired glucose tolerance, canakinumab had no effect compared with placebo on any of the measures assessed by using a standard oral glucose tolerance test. CONCLUSIONS There were no statistically significant effects of canakinumab on measures of vascular structure or function. Canakinumab reduced markers of inflammation (high-sensitivity C-reactive protein and interleukin-6), and there were modest increases in levels of total cholesterol and triglycerides. (Safety & Effectiveness on Vascular Structure and Function of ACZ885 in Atherosclerosis and Either T2DM or IGT Patients; NCT00995930).
4.
[Puerarin combined with avandia for diabetic nephropathy].
Hou, Q, Ao, X, Li, G, Zhang, Y
Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences. 2012;(1):73-7
Abstract
OBJECTIVE To observe the effect and mechanism of avandia and puerarin used in combination for diabetic nephropathy. METHODS A total of 180 patients with diabetic nephropathy were randomly divided into 3 groups. The control group (58 patients, group A) were treated with routine therapy including controlling the blood glucose and blood pressure, while 60 patients in group B were treated by avandia besides routine treatment of the control group. Anoter 62 cases in group C were administered with puerarin combined with avandia for 12 weeks. The indexes such as urea nitrogen, serum creatinine, triglyceride, cholesterol, low density lipoprotein, high density lipoprotein, mean arterial pressure, fasting blood glucose, 2h plasma glucose, glycosylated hemoglobin, and 24 h urinary albumin excretion rate were tested before and after the treatment . RESULTS No significant differences were found in the indexes such as triglyceride, serum cholesterol, low density lipoprotein, high density lipoprotein, glycosylated hemoglobin, malonaldehyde, erythrocuprein, blood urea nitrogen, serum creatinine and 24 h urinary albumin excretion rate among the 3 groups (P>0.05). There were no significant differences in all indexes before and after the treatment in group A (P>0.05) . After the treatment, 24 h urinary albumin excretion, urea nitrogen, serum creatinine, mean arterial pressure, fasting blood glucose, 2 h plasma glucose, glycosylated hemoglobin, triglyceride, serum cholesterol, low density lipoprotein decreased significant (P<0 05) while high density lipoprotein increased significant (P<0.05). CONCLUSION Avandia has better effect on adjusting the blood lipid and decreasing the urinary albumin excretion rate. Puerarin combined with avandia is more effective for improving the renal function and remission of islet function than using avandia alone. Puerarin and avandia have significant synergism.