Effects of acarbose on cardiovascular and diabetes outcomes in patients with coronary heart disease and impaired glucose tolerance (ACE): a randomised, double-blind, placebo-controlled trial

Holman, Rury R.; Coleman, Ruth L.; Chan, Juliana C.N.; Chiasson, Jean‐Louis; Feng, Huimei; Ge, Junbo; Gerstein, Hertzel C.; Gray, Richard; Huo, Yong; Lang, Zhihui; McMurray, John J.V.; Rydén, Lars; Schröder, Stefan; Sun, Yihong; Theodorakis, Michael J.; Tendera, Michał; Tucker, Lynne; Tuomilehto, Jaakko; Wei, Yidong; Yang, Wenying; Wang, Duolao; Hu, Dayi; Pan, Changyu; Keenan, Joanne F.; Milton, Joanne; Doran, Zoë; Bray, Chris; Rouleau, Jean L.; Collier, Jane; Pocock, Stuart; Standl, Eberhard; Swedberg, Karl; Weng, Jianping; Zhao, Dong; Petrie, Mark C.; Connolly, Eugene; Jhund, Pardeep S.; MacDonald, Michael R.; Myles, Rachel C.; Bai, Rong; Li, Jing; Liu, Zhaoping; Liu, Zhenyu; Peng, Dantao; Qiguang, Tong; Wang, Chunxue; Yan, Xiaowei; Zhang, Yuqing; Zhou, Jingmin; Sattar, Naveed; Fisher, Miles; Petrie, John R.; Bethel, M. Angelyn; Xu, Wen; Hearn, Sarah; Kappai, Anurag; Su, Shu-Yi; Liyanage, Winitha; Paul, Sanjoy K.; Pozzi, Emanuela; Ring, Arne; Athwal, Rajbir; Batra, Priyanka; Ferch, Andrea; Groves, N. D.; Kennedy, Irene; Nawalaniec, Olga; Patel, Yash; Roberts, Rachel; Rush, Victoria; Starrett, Jayne; Tang, Jennifer; Bi, Jing; Jiang, Zhe; Hua, Wei; Wei, Xiaoshuai; Zhang, Xuan; Yin, Jun; Sun, Yu; Hu, Rong; Liu, Yang; Long, Jianjing; Long, Yuefeng; Qiao, Guofang; Qiao, Haoyi; Sun, Xiaochun; Zhang, Yucheng; Zhou, Jing; Wang, Bangning; Chen, Bin; Deng, Lili; Han, Xiaoning; Hu, Taohong; Hua, Qi; Huo, Yanming; Li, Hongmei; Li, Hongwei; Liu, Lihua; Lu, Juming; Ma, Changsheng; Peng, Jianjun; Pi, Lin; Wang, Bin; Wei, Guanglin; Yang, Ming; Zhang, Shuyang; Zhang, Likun; Zhao, Xiaobin; Zhou, Yujie; Shi, Lei; Wang, Mingsheng; Wu, Lirong; Liu, Han; Liao, Ronghong; Ran, Boli; Qiang, Sheng; Tan, Jiancong; Mao, Xia; Yang, Chengming; Chen, Lianglong; Xiong, Shang-Quan; Yu, Ling; Pu, Xiaodong; Wang, Yan; Xie, Qiang; Ci-bin, Chen; Chen, Jiyan; Dong, Yugang; Wu, Zhaohui; Yuan, Yong; Zhou, Wan-xing; Zhou, Shuxian; Chen, Xiao-Chao; Wu, Chun Yi; Zhang, Aidong; Li, Zicheng; Lai, Sha-Yi; Yang, Jin; Wei, Jinru; Kuang, Riyu; Zhao, Zilin; Zhong, Guoqiang; Cao, Xufen; Hao, Yuming; Liu, Gang; Wang, Dongmei; Fang, Hui; Kong, Lingjun; Li, Haitao; Wang, Changqing; Wang, Lina; Li, Xueqi; Dong, Pingshuan; Zhang, Shouyan; Liu, Xincan; Zhao, Yang; Liu, Hengliang; Gu, Ye; Liao, Yuhua; Su, Xi; Wang, Daowen; Wang, Hairong; Yang, Bo; Guo, Ying; Ouyang, Ding-an; Yang, Tianlun; Zhang, Yumin; Han, Yajun; Lin, Xuefeng; Zhao, Ruiping; Man, Ronghai; Bian, Rongwen; Xu, Baojun; Hasimu, Buaijiaer; Jin, Hui; Liu, Ping; Yu, Jiangyi; Zhang, Hang; Xu, Chongli; Yan, Guo; Lv, Ke; Tao, Yijia; Xu, Xin; Yang, Zhenyu; Li, Dongye; Qi, Chunjian; Zhang, Guohui; Gu, Xianglin; Liu, Hong; Hu, Ling; Li, Juxiang; Yang, Ping; Liu, Bin; Wang, Gang; Lin, Hailong; Li, Jun; Zhang, Shuying; Ping, Han; Jin, Yuanzhe; Li, Ling; Li, Zhanquan; Luan, Hong; Song, Meijuan; Li, Xue; Yu, Hanjie; Liu, Dongwu; Yuan, Zuyi; Ye, Jixian; Gao, Feng; Feng, Jinhua; Wang, Ali; Ye, Shengming; Li, Xiaoyan; Su, Guohai; Zhang, Shufang; Hou, Zi-Shan; Jiang, Wenbin; Zhou, Chunxiao; Wang, Yanping; Qi, Wenbo; Bao, Xiaomei; Feng, Bo; Gong, Hui; Gu, Song; Gu, Min; Guo, Xiaoyun; He, Ben; Huang, Ying; Jiang, Jinfa; Jiang, Yifeng; Jin, Huigen; Li, Yuehua; Liu, Qiliang; Li, Guoping; Miao, Ping; Qin, Yong-wen; Yuan-ming, Wang; Wu, Shiyao; Xu, Yawei; Ma, Jianping; Chen, Xiaoping; Liu, Xiumin; Jia-ning, Tang; Wang, Jingping; Jian-hong, Tao; Zhang, Jun; Zhang, Tingjie; Li, Decai; Du, Xinping; Jiang, Tiemin; Lin, Jingna; Lu, Chengzhi; Ma, Hongjun; Gao, Bo; Xukun, Guo; Li, Tong; Shao-xiong, Zheng; Li, Zhongcheng; Zhao, Shuwu; Qiu, Qiang; Li, Kaili; Liu, Junming; Tang, Baopeng; Yuan, Zhanjun; Zhou, Jingbo; Bai, Wenwei; Guo, Tao; Zhang, Ge; Zhang, Hong; Hao, Yinglu; Fu, Guosheng; Tang, Lijiang; Chen, Jialun

doi:10.1016/s2213-8587(17)30309-1

Cited by 275 publications

(197 citation statements)

References 24 publications

(23 reference statements)

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“…This is consistent with evidence that a reduction in postprandial glucose excusions reduces CV risk and may refect an effect of acarbose to increase glucagon‐like peptide‐1 (GLP‐1) secretion . However, the recently completed 5‐year double‐blinded placebo‐controlled Acarbose Cardiovascular Evaluation (ACE) trial in 6522 Chinese patients with coronary heart disease and impaired glucose tolerance found no effect of acarbose on a five‐point composite MACE outcome of CV death, non‐fatal MI, non‐fatal stroke, hospital admission for unstable angina, and hospitalization for heart failure …”

Section: Antidiabetic Drugs and CV Effectssupporting

confidence: 73%

Cardiovascular protection in type 2 diabetes: Insights from recent outcome trials

Bailey

2018

Diabetes Obesity Metabolism

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This review examines recent randomized controlled cardiovascular (CV) outcome trials of glucose-lowering therapies in type 2 diabetes and their impact on the treatment of patients with type 2 diabetes. The trials were designed to comply with regulatory requirements to confirm that major adverse cardiac events (MACE) are not detrimentally affected by such therapies. Trials involving dipeptidyl peptidase-4 (DPP-4) inhibitors did not alter a composite MACE outcome comprising CV deaths, non-fatal myocardial infarction and non-fatal stroke; however, the possibility that some members of this class might incur a small increased risk or worsening of heart failure cannot be excluded. Some studies on glucagon-like peptide-1 receptor agonists (liraglutide: LEADER trial; semaglutide: SUSTAIN-6 trial) found significant benefits for MACE, while treatment with sodium-glucose co-transporter-2 inhibitors (empagliflozin: EMPA-REG OUTCOME trial; canagliflozin: CANVAS trial) also significantly reduced MACE and reduced hospitalization for heart failure. Comparisons among trials are complicated by variance in the populations recruited, particularly CV status at randomization, and differences in trial design, data collection and analyses. A large proportion of patients recruited into these trials have previously experienced adverse CV events; thus, the therapies are mostly assessing secondary prevention of a further event. This contrasts with the overall type 2 diabetes population receiving glucose-lowering therapies, of whom the majority will not have had MACE and will be regarded as primary prevention. Overall, the trials provide reassuring evidence that new glucose-lowering medications do not adversely affect CV events and some of these agents may offer CV protection.

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Section: Antidiabetic Drugs and CV Effectssupporting

confidence: 73%

Cardiovascular protection in type 2 diabetes: Insights from recent outcome trials

Bailey

2018

Diabetes Obesity Metabolism

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“…To date, 17 randomized CVOTs have been completed, and all have confirmed non-inferiority for the therapies assessed in terms of CV safety when compared with placebo. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] In addition, five of the 17 completed CVOTs have also confirmed significant reductions in the primary MACE composite endpoint for the sodium-glucose cotransporter-2 (SGLT2) inhibitors empagliflozin and canagliflozin, 8,14 and for the glucagon-like peptide-1 receptor agonists (GLP-1RAs) liraglutide, albiglutide and dulaglutide, 16,18,19 suggesting that these agents have direct cardioprotective properties. A sixth study, the SUS-TAIN 6 trial, reported CV superiority compared to placebo for the GLP-1RA semaglutide in a post hoc analysis.…”

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confidence: 99%

Real‐world prevalence of the inclusion criteria for the LEADER trial: Data from a national general practice network

Hinton

Feher

Munro

et al. 2019

Diabetes Obesity Metabolism

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Aims To explore the prevalence and describe the clinical characteristics of people with type 2 diabetes with a similar cardiovascular (CV) profile to that of the LEADER trial participants in a primary care setting in England. Materials and methods In this cross‐sectional analysis, using the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) network database, we identified people with type 2 diabetes meeting the LEADER inclusion criteria. We identified people's CV risk factors using computerized medical records. Additionally, we assessed the prescription pattern of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) in this cohort. Results Of 1 275 461 adults, we identified 84 394 with type 2 diabetes, of whom 14 000 (16.6%) met the LEADER inclusion criteria for established or high‐risk CV disease (RCGP RSC‐CVD group). The LEADER cohort was younger than the RCGP RSC‐CVD group (64.2 vs 73.2 years), had higher mean glycated haemoglobin (71.6 vs 67.1 mmol/mol) and blood pressure (BP) values (systolic BP: 135.9 vs 132.9 mmHg; diastolic BP: 77.2 vs 72.7 mmHg), and a higher mean body mass index (32.5 vs 30.9 kg/m 2 ). In the RCGP RSC‐CVD group, only 1215 people (8.7%) had ever been prescribed a GLP‐1RA and 760 (5.4%) had ever received liraglutide. Conclusions In a cohort of English general practice patients, one in six people with type 2 diabetes met the LEADER inclusion criteria, and less than one in 10 of these received liraglutide, a drug which has demonstrated CV benefits amongst others. There is scope to improve the outlook in people with type 2 diabetes and high CV risk through evidence‐based use of specific GLP‐1RAs.

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“…Currently, several compounds are used medically to suppress hyperglycemia, including acarbose, miglitol, and voglibose (Holman et al., ; Ismail & Deshmukh, ). Acarbose inhibits α‐amylase and α‐glucosidase activity, and is used in research as well as clinically (Puls, Keup, Krause, Thomas, & Hoffmeister, ; Schmidt et al., ).…”

Section: Introductionmentioning

confidence: 99%

Isolation and Characterization of Antihyperglycemic Compounds from Vigna angularis Extracts

Kuriya

Nishio

Ono

et al. 2019

Journal of Food Science

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Functional foods that inhibit α‐amylase and α‐glucosidase activity are effective for regulating the blood glucose level and preventing hyperglycemia. Extracts of adzuki beans (ABs, Vigna angularis), widely eaten in East Asia, can inhibit α‐amylase and α‐glucosidase activity. In this study, we identified and evaluated the components in an AB water extract (ABWE) after boiling, which is an essential process for cooking ABs. The ABWE before boiling inhibited α‐amylase and α‐glucosidase activity and the boiled ABWE showed slightly stronger inhibitory effects. High‐performance liquid chromatography, liquid chromatography‐mass spectrometry, and nuclear magnetic resonance analyses identified (+)‐catechin 7‐O‐β‐d‐glucopyranoside (C7G), (+)‐epicatechin 7‐O‐β‐d‐glucopyranoside (E7G), and (+)‐catechin as the bioactive components in boiled ABWE. Interestingly, the quantity of E7G significantly increased after boiling (from 0% to 17.1 ± 1.3%). E7G showed stronger inhibition of α‐amylase and α‐glucosidase than C7G; the IC50 values for α‐amylase were 0.74 ± 0.04 mg/mL (C7G) and 0.40 ± 0.09 mg/mL (E7G), and for α‐glucosidase the IC50 values were 0.085 ± 0.032 mg/mL (C7G) and 0.051 ± 0.007 mg/mL (E7G). Our findings suggest that C7G and E7G are the main active components in ABWE as they inhibit α‐amylase and α‐glucosidase and their inhibitory effect is not lost after boiling. These results support the effectiveness of boiled ABs in the promotion of health. Practical Application We identified (+)‐catechin 7‐O‐β‐d‐glucopyranoside (C7G), (+)‐epicatechin 7‐O‐β‐d‐glucopyranoside (E7G), and (+)‐catechin in adzuki bean extracts and commercially available boiled adzuki bean products. Interestingly, the E7G content was increased by boiling, and this compound showed strong inhibitory activity toward α‐amylase and α‐glucosidase. These results support the consumption of boiled adzuki beans to prevent acute rises in blood glucose level.

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Effects of acarbose on cardiovascular and diabetes outcomes in patients with coronary heart disease and impaired glucose tolerance (ACE): a randomised, double-blind, placebo-controlled trial

Abstract: Bayer AG.

Cited by 275 publications

References 24 publications

Cardiovascular protection in type 2 diabetes: Insights from recent outcome trials

Cardiovascular protection in type 2 diabetes: Insights from recent outcome trials

Real‐world prevalence of the inclusion criteria for the LEADER trial: Data from a national general practice network

Isolation and Characterization of Antihyperglycemic Compounds from Vigna angularis Extracts

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