Search

Aims/Introduction: The prevalence and pathophysiological background of type 2 diabetes mellitus vary across ethnicities, and can affect treatment responses. Adding lixisenatide to basal insulin (BI) in type 2 diabetes mellitus patients has shown improvements in glycated hemoglobin (HbA1c) and postprandial glycemic (PPG) excursions, without increasing hypoglycemic events. We aim to compare the efficacy of lixisenatide in Asian and white patients inadequately controlled with basal insulin. Materials and Methods: An individual‐level pooled analysis of two multi‐national phase III studies, GetGoal‐L and GetGoal‐L‐C, was carried out to assess the efficacy of lixisenatide versus placebo as an add‐on treatment to BI ± metformin in Asian and white patients with type 2 diabetes mellitus. Change in HbA1c, 2‐h PPG and PPG excursion were analyzed, along with possible predictors of glycemic control. Results: Pooled data showed that baseline characteristics were similar between Asian and white patients with the exception of bodyweight, body mass index and BI dose being higher in white patients. After 24 weeks, lixisenatide reduced HbA1c in both ethnic groups, with no statistically significant difference between the two groups (Asian patients least squares mean difference −0.49, 95% confidence interval −0.68 to − 0.30 and white patients least squares mean difference −0.45, 95% confidence interval −0.63 to − 0.26; P = 0.6287). Similarly, no significant difference was found in 2‐h PPG reduction between both groups (least squares mean difference for Asian vs white patients: −3.37 vs −3.93; P = 0.3203). Treatment with lixisenatide contributed to HbA1c reduction of −0.56% after adjustment of baseline HbA1c level in Asian patients, and −0.41% in white patients. Conclusions: Adding lixisenatide to BI significantly reduced HbA1c and 2‐h PPG levels in both Asian and white participants with type 2 diabetes mellitus. No differences in treatment effect were observed between the two populations. [ABSTRACT FROM AUTHOR]

Introduction: China has the world's largest diabetes epidemic and has been facing a serious shortage of primary care providers for chronic diseases including diabetes. To help primary care physicians follow guidelines and mitigate the workload in primary care communities in China, we developed a guideline-based decision tree. This study aimed to validate it at 3 months with real-world data. Methods: The decision tree was developed based on the 2017 Chinese Type 2 Diabetes (T2DM) guideline and 2018 guideline for primary care. It was validated with the data from two registry studies: the NEW2D and ORBIT studies. Patients' data were divided into two groups: the compliance and non-compliance group, depending on whether the physician's prescription was consistent with the decision tree or not. The primary outcome was the difference of change in HbA1c from baseline to 3 months between the two groups. The secondary outcomes included the difference in the proportion of patients achieving HbA1c < 7% at 3 months between the two groups, the incidence of self-reported hypoglycemia at 3 months, and the proportion of patients (baseline HbA1c ≥ 7%) with a HbA1c reduction ≥ 0.3%. The statistical analysis was performed using linear or logistic regression with inverse probability of treatment weighting with adjustments of confounding factors. Results: There was a 0.9% reduction of HbA1c in the compliance group and a 0.8% reduction in the non-compliance group (P < 0.001); 61.1% of the participants in the compliance group and 44.3% of the participants in the non-compliance group achieved a HbA1c level < 7% at 3 months (P < 0.001). The hypoglycemic events occurred in 7.1% of patients in the compliance group vs. 9.4% in the non-compliance group (P < 0.001). Conclusion: The decision tree can help physicians to treat their patients so that they achieve their glycemic targets with fewer hypoglycemic risks. (http://www.clinicaltrials.gov NCT01525693 & NCT01859598). [ABSTRACT FROM AUTHOR]

Introduction: Simultaneous administration of acetylsalicylic acid (ASA) and clopidogrel has demonstrated efficacy in the treatment of acute coronary syndrome. Clopidogrel + ASA in a fixed-dose combination (FDC) provides a pharmaceutical option to enhance adherence to the coadministration of dual antiplatelet therapy (DAPT). Herein, we evaluate the bioequivalence of enteric ASA and clopidogrel in an FDC compared with simultaneous administration of the individual formulations. Methods: This study is a randomized, single-center, open-label, three-sequence, three-period, two-treatment, crossover study conducted in healthy Chinese male and female subjects under fed conditions. Subjects were randomized to receive, in each period, a single dose of (1) a combination tablet containing 75-mg clopidogrel and 100-mg enteric ASA (test formulation) or (2) coadministration of one 75-mg clopidogrel tablet and one 100-mg enteric-coated ASA tablet (reference formulations) under fed conditions. Plasma samples were analyzed for ASA, salicylic acid, clopidogrel, and the clopidogrel metabolite SR26334. For ASA, the reference-scaled average bioequivalence (RSABE) analysis was conducted for Cmax of ASA because within-subject standard deviation (SDW) was ≥ 0.294 for log-transformed Cmax. Results: The point estimate (test/reference geometric mean ratio) was between 0.80 and 1.25, and the upper one-sided 95% confidence interval (CI) for the scaled average bioequivalence metric was ≤ 0 (-0.08). AUC of ASA as SDW was < 0.294 for log-transformed AUClast and AUC. Estimates of 90% CIs for log-transformed AUClast and AUC ratios were within the bioequivalence range of 0.80 to 1.25 (0.98–1.08 and 1.00–1.10, respectively). For clopidogrel, the 90% CIs for the ratios comparing log-transformed Cmax, AUClast, and AUC ratios of clopidogrel following administration of test versus reference formulation were calculated using the ABE method and were well within the acceptable range of 0.80 to 1.25 (1.02–1.12, 0.92–0.99, and 0.92–0.98, respectively). Conclusion: FDC of ASA and clopidogrel was bioequivalent to the simultaneous administration of the individual formulations in healthy Chinese subjects under fed conditions. Trial registration: CTR20190376. [ABSTRACT FROM AUTHOR]

Introduction: Dual antiplatelet therapy, aspirin and a P2Y12 inhibitor, is recommended to prevent thrombotic complications of acute coronary syndrome. Clopidogrel plus acetylsalicylic acid combination is the most commonly used dual antiplatelet therapy recommended by international guidelines and in Chinese clinical practice. Poor adherence to dual antiplatelet therapy or premature interruption of dual antiplatelet therapy is an important contributor to cardiovascular mortality and lethal cardiovascular events. Clopidogrel + acetylsalicylic acid fixed-dose combination enhances adherence to dual antiplatelet therapy. Herein, we aimed to evaluate bioequivalence of acetylsalicylic acid and clopidogrel in fixed-dose combination compared with simultaneous administration of their individual formulations in healthy Chinese subjects under fasting conditions.Methods: This was a randomized, single-center, open-label, three-sequence, three-period, two-treatment, crossover study with a washout period of 10 days conducted in healthy Chinese volunteers. Subjects were randomized to receive Co-Plavix® (test formulation- fixed-dose combination of 100 mg acetylsalicylic acid and 75 mg clopidogrel) once and reference formulations (coadministration of individual formulations of 100 mg acetylsalicylic acid and 75 mg clopidogrel) twice during the study period. Pharmacokinetic parameters were analyzed for acetylsalicylic acid, its metabolite salicylic acid, clopidogrel, and its metabolite SR26334. As acetylsalicylic acid shows high intrasubject variability, the reference-scaled average bioequivalence (RSABE) approach was implemented for acetylsalicylic acid analysis, while bioequivalence of clopidogrel was assessed using the average bioequivalence method. Point ratios and confidence intervals (CIs) for AUC, AUClast, and Cmax for acetylsalicylic acid and clopidogrel were calculated.Results: In total, 171 healthy subjects were enrolled in this study. Subjects were randomized and 170 subjects were treated with test or reference formulation; 164 subjects completed the study. Regarding acetylsalicylic acid exposure, as reference within-subject standard deviation (SDW) was at least 0.294 for acetylsalicylic acid Cmax, AUClast, and AUC, the RSABE analysis method was used to assess bioequivalence for all three parameters. The point estimates were within the 0.80-1.25 range (1.19, 1.09, and 1.04, respectively), and upper one-sided 95% CIs of scaled average bioequivalence metric were at most 0 (- 0.30, - 0.14, and - 0.10, respectively). Thus, bioequivalence was demonstrated with acetylsalicylic acid. Bioequivalence was also achieved with clopidogrel as the 90% CIs for geometric mean ratios of clopidogrel Cmax, AUClast, and AUC were within the bioequivalence range (0.80-1.25).Conclusion: Application of the reference-scaled average bioequivalence approach to evaluate bioequivalence of acetylsalicylic acid in Chinese male and female healthy volunteers under fasting conditions demonstrated bioequivalence of test and reference formulations.Trial Registration: CTR20181695. [ABSTRACT FROM AUTHOR]

Ischemic heart disease is one of the leading causes of morbidity and mortality worldwide. Shu-mai-tang (SMT) is a traditional Chinese medicine for the treatment of ischemic heart disease. To better understand the underlying cardioprotection mechanisms of SMT on myocardial ischemia (MI), the effect of SMT on angiogenesis, arteriogenesis and cardiac function was investigated in a rat model of MI, as well as the potential mechanism. Rats with a ligated left anterior descending coronary artery (MI model) were randomized (24 rats/group) to receive SMT/LY294002 [phosphatidylinositol 3-kinase (PI3K) inhibitor], SMT or no treatment. A sham-operation group was included. It was demonstrated that 2 and 4 weeks after treatment the oral administration of SMT significantly increased capillaries and arterioles, suppressed myocardial fibrosis, as well as significantly increased cardiac phosphorylation of Akt, vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF-BB) levels and functional improvement. PI3K inhibitor down-regulated SMT-induced angiogenesis and arteriogenesis. These novel therapeutic properties of SMT to induce the reconstitution of stable blood supply networks, reverse LV remodeling may offer an alternative therapy for the treatment of ischemic heart disease. The potential mechanism may be that SMT promotes VEGF and PDGF-BB-mediated angiogenesis and arteriogenesis through the PI3K/Akt signaling pathway. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Ginkgo biloba extract (GBE) has been widely used to treat cardiovascular and cerebrovascular disorders. Hyperhomocysteinemia (Hhcy) is associated with the risk of atherosclerosis and restenosis after angioplasty. The objective of this study was to investigate whether GBE could attenuate the Hhcy-induced intimal thickening after balloon injury in rabbit abdominal aorta. It was observed in this study that GBE could decrease the neointima area (NA) and the ratio of the neointima area to the media area (NA/MA), down-regulate the mRNA expression of matrix metalloproteinase-9 (MMP-9) and up-regulate the protein expression of p21 WAF1/CIP1 (p21). It suggests that GBE can reverse the Hhcy-induced neointima formation in rabbits following balloon injury, and the suppressive effect of GBE on the migration and proliferation of vascular smooth muscle cells (VSMCs) may contribute to its actions. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Premixed insulin is the most commonly used insulin in China. This trial compared the efficacy and safety of once-daily insulin glargine 100 U/mL (Gla-100) + oral antihyperglycemic drugs (OADs) and twice-daily insulin aspart 70/30 (Asp 30) + OAD in T2D patients. Chinese adults with T2D receiving stable doses of metformin and 1-2 OADs with HbA1c 7.5%-11.0% were enrolled and entered a 7-10 day SIT period in which they were treated with basal-bolus to achieve a fasting blood glucose (FBG) <7 mmol/L and 2-hour postprandial glucose (2hPG) <10 mmol/L. Patients were then randomized 1:1 to receive Gla-100 + OADs (n=192) or Asp 30 + OAD (n=192) for 24 weeks. Baseline characteristics were balanced across groups. Mean (SD) age was 54.2 (8.8) years, BMI was 26.0 (3.1) kg/m2, and duration of diabetes was 6.8 (3.0) years. At week 24, the least square mean (SE) change from baseline in HbA1c was -1.72% (0.07) and -1.70% (0.07) in the Gla-100 and Asp 30 groups, respectively (Table); group difference (-0.01%; 95% CI -0.20, 0.17) met the pre-specified non-inferiority criteria (upper bound 95% CI <0.4%). All hypoglycemia events were significantly lower in the Gla-100 group. In conclusion, compared with Asp 30 + OAD, Gla-100 + OAD showed similar efficacy but lower hypoglycemia risk in Chinese T2D patients. Disclosure: Y. Mu: Speaker's Bureau; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk Inc., Sanofi-Aventis. J. Liu: Employee; Self; Sanofi China. X. Zhang: None. N. Cui: Employee; Self; Sanofi China. H. Yin: None. L. Guo: Consultant; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., BD, Eli Lilly and Company, Merck & Co., Inc., Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk, Sanofi China. H. Wan: None. J. Wang: None. B. Xu: None. G. Wang: None. C. Jiang: None. L. Liang: None. W. Feng: Employee; Self; Sanofi China. Funding: Sanofi China (NCT03359837) [ABSTRACT FROM AUTHOR]

To titrate basal and bolus insulin sequentially or simultaneously during SIT remains controversial. Here we report an easy titration order verified in a 7-10 day SIT period. Insulin naïve Chinese T2D adults receiving stable doses of metformin and 1-2 oral antihyperglycemic drugs with HbA1c 7.5%-11.0% were treated with once-daily insulin glargine 100 U/mL (Gla-100) and thrice-daily insulin glulisine (Glu) for 7-10 days titrated to achieve a fasting blood glucose (FBG) <7 mmol/L and 2-hour postprandial glucose (2hPG) <10 mmol/L. Gla-100 was titrated first until FBG achieved 4.4-6.1 mmol/L, then Glu was titrated to achieve pre-meal blood glucose 4.4-6.1 mmol/L. Of 466 patients screened, 397 entered the SIT period; 391 (98.5%) completed. Baseline mean (SD) age was 54.2 (8.8) years, duration of disease was 6.8 (3.0) years, BMI was 26.0 (3.2) kg/m2, HbA1c was 9.1% (1.1), and FBG was 10.7 (2.5) mmol/L; 59.2% were male. Overall, 94.4% of patients achieved the predefined target at the end of the SIT period (Table). The mean time to first achieving 2hPG target was less than the time to first achieving FBG target, implying that titrating basal insulin first could minimize Glu dose increases and potential hypoglycemia risk. In conclusion, when starting basal-bolus regimen in SIT, basal-first titration order was effective, fast to target and well tolerated in Chinese T2D patients. Disclosure: L. Guo: Consultant; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., BD, Eli Lilly and Company, Merck & Co., Inc., Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk, Sanofi China. J. Liu: Employee; Self; Sanofi China. X. Zhang: None. N. Cui: Employee; Self; Sanofi China. H. Yin: None. Y. Mu: Speaker's Bureau; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk Inc., Sanofi-Aventis. H. Wan: None. J. Wang: None. B. Xu: None. G. Wang: None. C. Jiang: None. L. Liang: None. W. Feng: Employee; Self; Sanofi China. Funding: Sanofi China (NCT03359837) [ABSTRACT FROM AUTHOR]

The article announces the retraction of the article "Ginsenoside-Rg1 enhances angiogenesis and ameliorates ventricular remodeling in a rat model of myocardial infarction," by Huiqiu Yin and colleagues that was published in the 2011 issue.