Efficacy and Safety of Mulberry Twig Alkaloids Tablet for Treatment of Type 2 Diabetes: A Randomized, Double-Blind,Placebo-Controlled Multicenter Clinical Study

Ling QU; Xiao-chun LIANG; Guo-qing TIAN; Gai-li ZHANG; Qun-li WU; Xiu-mei HUANG; Ya-zhong CUI; Yu-ling LIU; Zhu-fang SHEN; Guo-qing MA; Hao LU; Yi LI; Hong JIANG; Xi-yan YANG; Guang-de ZHANG; Chen-hua YANG

doi:10.1007/s11655-021-2885-9

Your Location：

Home >

Browse articles >

Efficacy and Safety of Mulberry Twig Alkaloids Tablet for Treatment of Type 2 Diabetes: A Randomized, Double-Blind,Placebo-Controlled Multicenter Clinical Study

Original Article | Updated：2022-03-29

- Efficacy and Safety of Mulberry Twig Alkaloids Tablet for Treatment of Type 2 Diabetes: A Randomized, Double-Blind,Placebo-Controlled Multicenter Clinical Study
- Chinese Journal of Integrative Medicine Vol. 28, Issue 4, Pages: 304-311(2022)
- Affiliations：
  
  1.Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (100730) China
  2.Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing (100050), China
  3.Department of Endocrinology,the Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Haerbin (150001), China
  4.Department of Endocrinology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai (201203), China
  5.Department of Traditional Chinese Medicine, Beijing Hospital,Beijing (10005), China
  6.Department of Endocrinology, the Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang (110034), China
  7.Department of Geriatrics, the First Affiliated Hospital of Tianjin University of Chinese Medicine, Tianjin (300073), China
  8.Department of Endocrinology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing (100091), China
  9.Department of Endocrinology, Affiliated Hospital of Henan Academy of Traditional Chinese Medicine, Zhengzhou (450003), China
- Author bio：
  
  Prof. LIANG Xiao-chun, E-mail: Xiaochun_Liang@yeah.net
- Funds：
- DOI：10.1007/s11655-021-2885-9
  CLC：
- Published：2022-04，
  
  Published Online：19 January 2022，
  
  Accepted：06 September 2021
Scan for full text
Ling QU, Xiao-chun LIANG, Guo-qing TIAN, et al. Efficacy and Safety of Mulberry Twig Alkaloids Tablet for Treatment of Type 2 Diabetes: A Randomized, Double-Blind,Placebo-Controlled Multicenter Clinical Study. [J]. Chinese Journal of Integrative Medicine 28(4):304-311(2022)
DOI：

Ling QU, Xiao-chun LIANG, Guo-qing TIAN, et al. Efficacy and Safety of Mulberry Twig Alkaloids Tablet for Treatment of Type 2 Diabetes: A Randomized, Double-Blind,Placebo-Controlled Multicenter Clinical Study. [J]. Chinese Journal of Integrative Medicine 28(4):304-311(2022) DOI： 10.1007/s11655-021-2885-9.

摘要

目的

通过多中心随机双盲安慰剂对照试验评价桑枝总生物碱片 (Sangzhi alkaloids

SZ-A) 治疗2型糖尿病患者的有效性和安全性.

方法

200例受试者被随机分成桑枝总生物碱片组 (

=100) 和安慰剂对照组 (

=100) 组

干预时间16周. 采用DAS临床试验中央随机系统申请随机号和配发药物. 主要疗效指标包括治疗后的HbA1c水平较基线的变化

次要疗效指标包括治疗后HbA1c

7%和

6.5%的比例

空腹血糖 (静脉血浆

FBG) 、餐后1h血糖 (静脉血浆

1h-PBG) 、餐后2h血糖 (静脉血浆

2h-PBG) 、餐后血糖曲线下面积 (AUC

0-2h

) 、体重及体重指数 (BMI) 较基线变化值及实测值. 安全性指标包括不良事件 (AEs) 、严重不良事件 (SAEs) 、治疗相关不良事件 (TAEs) 及胃肠道症状 (GDs) 的发生率

两组间治疗后血压、血常规、肝肾功能较本组基线变化值的差异.

结果

治疗16周后SZ-A组HbA1c较基线变化值-0.80% (95% CI-0.98%~-0.62%)

安慰剂组-0.09% (95% CI-0.27%~0.09%)

协方差分析组间比较差异具有统计学意义 (

0.001) . SZ-A组HbA1c

7%和6.5%达标率分别为46.8%和29.9%

均高于安慰剂组 (21.6%和10.8%)

两组间比较差异均具有统计学意义 (

=0.001

=0.003) . 治疗16周时FPG、1h-PBG、2h-PBG及AUC

0-2h

实测值和较基线变化值于SZ-A组与安慰剂比较

差异均具有统计学意义 (

0.001) . 两组间体重和BMI比较无统计学差异 (

0.05) . AEs、TAEs及GDs发生率两组间比较差异有统计学意义 (

=0.010

=0.005

=0.006) . SAEs发生率两组间比较差异均无统计学意义(

=1.000).

结论

SZ-A是一种有效的治疗2型糖尿病的药物

安全性良好. 项目注册http://www.chictr.org.cn/showproj.aspx?proj=60117 (ChiCTR2000038550).

Abstract

Objective:

To assess the efficacy and safety of mulberry twig alkaloids (Sangzhi alkaloids

SZ-A) for treatment of type 2 diabetes in a randomized

double-blind

placebo-controlled multicenter clinical trial.

Methods:

A total of 200 patients were randomized to receive SZ-A (

=100) or placebo (

=100) for 16 weeks. The data analysis system for electronic data capture clinical trial central randomization system was used for randomization and dispensing of drugs. The primary outcome was the change in glycosylated hemoglobin (HbA1c) level. The secondary outcome included the proportions of cases with HbA1c

7.0% and HbA1c

6.5%

fasting blood glucose (FBG)

postprandial blood glucose (PBG)

area under curve for the PBG (AUC

0-2h

)

body weight

and body mass index (BMI). Adverse events (AEs)

severe adverse events (SAEs)

treatment-related adverse events (TAEs)

gastrointestinal disorders (GDs)

blood pressure

routine blood tests

and liver and kidney function were monitored.

Results:

Compared with baseline

the change of HbA1c at week 16 was –0.80% (95% CI: –0.98% to –0.62%) and –0.09% (95% CI: –0.27% to 0.09%) in SZ-A group and placebo group

respectively. The proportion of patients with HbA1c

7% and

6.5% was higher in the SZ-A group than in the placebo group (46.8% vs. 21.6% and 29.9% vs. 10.8%). The observed values and changes in FBG

1 h-PBG

2 h-PBG

and AUC

0-2h

differed significantly between groups (

0.001)

but differences were not significant in body weight and BMI (

0.05). The incidence rates of AEs

TAEs

and GDs differed significantly between groups (

=0.010

=0.005

and

=0.006

respectively)

whereas the incidence rates of SAEs showed no significant differences between groups (

=1.000).

Conclusion:

SZ-A are effective and safe for treatment of type 2 diabetes. [The protocol was registered in http://www.chictr.org.cn/showproj. aspx?proj=60117 (ChiCTR2000038550)]

关键词

Keywords

type 2 diabetes mellitusmulberry twig alkaloids tablets (Sangzhi alkaloids)efficacysafetyplacebo

references

Diabetes Atlas E.E.C., IDF Diabetes Atlas. 9th edition 2019. 2019.

World Health Organization. Global report on diabetes. WHO, 2016. https://apps.who.int/iris/handle/10665/204874https://apps.who.int/iris/handle/10665/204874.

Mahboubi M. Morus alba (mulberry), a natural potent compound in management of obesity. Pharmacol Res 2019;146:104341.

Thaipitakwong T, Supasyndh O, Rasmi Y, Aramwit P. A randomized controlled study of dose-finding, efficacy, and safety of mulberry leaves on glycemic profiles in obese persons with borderline diabetes. Complement Ther Med 2020;49:102292.

Ye F, Shen ZF, Xie MZ. Alpha-glucosidase inhibition from a Chinese medical herb (Ramulus mori) in normal and diabetic rats and mice. Phytomedicine 2002;9:161-166.

Ye F, Shen ZF, Qiao FX, Zhao DY, Xie MZ, et al.Experimental treatment of complications in alloxan diabetic rats with alpha-glucosidase inhibitor from the Chinese medicinal herb Ramulus mori. Acta Pharmaceut Sin 2002;37:108-112.

Liu SN, Liu Q, Sun SJ, Li CN, Huan Y, Chen YT, et al. Anti-diabetic effects of the fraction of alkaloids from Ramulus Mori, an innovative Sangzhi alkaloids as an α-glucosidase inhibitor. Acta Pharmaceut Sin 2019;7:1225-1233.

Qu L, Liang XC, Tian GQ, Zhang GL, Wu QL, Huang XM, et al. Efficacy and safety of Mulberry Twig Alkaloids Tablet for the treatment of type 2 diabetes: A multicenter,randomized, double-blind, double-dummy, and parallel controlled clinical trial. Diabetes Care 2021;44:1324–1333.

Rodrigues EL, Marcelino G, Silva GT, Figueiredo PS,Garcez WS, Corsino J, et al. Nutraceutical and medicinal potential of the morus species in metabolic dysfunctions. Int J Mol Sci 2019;14;20:301.

Chan EW, Lye PY and Wong SK. Phytochemistry,pharmacology, and clinical trials of Morus alba. Chin J Nat Med 2016;14:17-30.

Zhang L, Tao GJ, Chen J, Zheng ZP. Characterization of a new flavone and tyrosinase inhibition constituents from the Twigs of Morus alba L. Molecules 2016;21:1130.

Yang S, Mi JQ , Liu ZH, Wang BL, Xia XJ, Wang RY, et al.Pharmacokinetics, tissue distribution, and elimination of three active alkaloids in rats after oral administration of the effective fraction of alkaloids from ramulus mori, an innovative hypoglycemic agent. Molecules 2017;22:1616.

American Diabetes Association. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2019. Diabetes Care 2019;42(Suppl 1):S90-S102.

Ko SH, Hur KY, Rhee SY, Kim NH, Moon MK, Park SO,et al. Antihyperglycemic agent therapy for adult patients with type 2 diabetes mellitus 2017: a position statement of the Korean diabetes association. Diabetes Metab J 2017;41:337-348.

Garber AJ, Abrahamson MJ, Barzilay JI, Blonde L,Bloomgarden ZT, Bush MA, et al. Consensus statement by the american association of clinical endocrinologists and american college of endocrinology on the comprehensive type 2 diabetes management algorithm–2019 executive summary. Endocr Pract 2019;25:69-100.

Liu ZH, Yang Y, Dong WJ, Liu Q, Wang RY, Pang JM, et al.Investigation on the enzymatic profile of mulberry alkaloids by enzymatic study and molecular docking. Molecules 2019;24i:E1776.

Yang S, Wang BL, Xia XJ, Li X, Wang RY, Sheng L, et al.Simultaneous quantification of three active alkaloids from a traditional Chinese medicine Ramulus mori (sangzhi)in rat plasma using liquid chromatography-tandem mass spectrometry. J Pharm Biomed Anal 2015;109:177-183.

Gao K, Zheng CL, Wang T, Zhao HH, Wang J, Wang ZY,et al. 1-Deoxynojirimycin: occurrence, extraction, chemistry,oral pharmacokinetics, biological activities and in silico target fishing. Molecules 2021;21:1600.

More>

Views

Downloads

CSCD

Alert me when the article has been cited

Submit

Tools

Publicity Resources

Efficacy and Safety of Jianpi Jieyu Decoction for Patients with Mild-to-Moderate Depression of Xin (Heart)-Pi (Spleen) Deficiency Syndrome: A Multi-centre Randomized Controlled Study

Clean-DM1, a Korean Polyherbal Formula, Improves High Fat Diet-Induced Diabetic Symptoms in Mice by Regulating IRS/PI3K/AKT and AMPK Expressions in Pancreas and Liver Tissues

Indian Traditional Treatments for Psoriasis: A Critical Appraisal of Available Evidence Supporting Efficacy

Effect and Safety of Acupuncture for Type 2 Diabetes Mellitus:A Systematic Review and Meta-analysis of 21 Randomised Controlled Trials

Modified Linggui Zhugan Decoction Ameliorates Glycolipid Metabolism and Inflammation via PI3K-Akt/mTOR-S6K1/AMPK-PGC-1α Signaling Pathways in Obese Type 2 Diabetic Rats

Related Author

No data

Related Institution

Department of Nephrology, Pinggu Hospital, Beijing Hospital of Traditional Chinese Medicine

Institute of Basic Medicine, Xiyuan Hospital, China Academy of Chinese Medical Sciences

Department of Encephalopathy, Botou Traditional Chinese Medicine Hospital of Hebei Province

Institute of Clinical Pharmacology, Xiyuan Hospital, China Academy of Chinese Medical Sciences

First College of Clinical Medicine, Shandong University of Traditional Chinese Medicine

Address：1 Caochang, xiyuan, Beijing, People's Republic of China Postal code：100091
Tel：010-62886827, 62877592 Fax：010-62874291
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备05067934号-1 京公网安备11010802024621
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰