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Efficacy and safety of voglibose in comparison with acarbose in type 2 diabetic patients

Efficacy and safety of voglibose in comparison with acarbose in type 2 diabetic patients
Efficacy and safety of voglibose in comparison with acarbose in type 2 diabetic patients

Diabetes Research and Clinical Practice 55(2002)99–103

Ef?cacy and safety of voglibose in comparison with

acarbose in type 2diabetic patients

Apichati Vichayanrat *,Sirirat Ploybutr,Monchaya Tunlakit,

Praneet Watanakejorn

Di 6ision of Endocrinology and Metabolism ,Department of Medicine ,Faculty of Medicine &Siriraj Hospital ,Mahidol Uni 6ersity ,

Bangkok 10700,Thailand

Accepted 18June 2001

Abstract

We performed a randomized crossover open comparative study to evaluate the ef?cacy and safety of voglibose and acarbose in 30patients with type 2diabetes who were not well controlled with diet therapy.There was no signi?cant reduction of FBG with either voglibose or acarbose at 4and 8weeks after treatment.The 1h postprandial blood glucose (PPBG)level was signi?cantly decreased from 224.9942.8to 204.1937.6(P =0.005)and 206.1938.9mg /dl (P =0.038)after voglibose therapy at 4and 8weeks,respectively.Signi?cant decrease was also obtained after acarbose treatment from 228.3937.4to 182.7935.5(P B 0.001)and 186.6936.1mg /dl (P B 0.001).The decrease of 1h PPBG was associated with a signi?cant fall of serum insulin concentration.HbA 1c levels were also signi?cantly decreased from 7.0791.21to 6.8391.11(P =0.017)and 6.7991.33%(P =0.036)after voglibose and 6.9890.98to 6.7091.04(P B 0.001)and 6.5991.04%(P B 0.001)after acarbose at 4and 8weeks.In contrast to voglibose,treatment with acarbose signi?cantly decreased the 2h PPBG at 4and 8weeks and the 2h postprandial serum insulin concentration at 8weeks.Adverse drug events were more commonly reported in acarbose-treated patients (P B 0.05).Increased ?atulency was observed in 56.7and 90%of the patients taking voglibose and acarbose,respectively,while abdominal distention was noted in 10and 16.7%.Signi?cantly decreased body weights of 0.9and 0.8kg were recorded at 8weeks after voglibose and acarbose therapy,respectively.We conclude that both voglibose (0.2mg)and acarbose (100mg)thrice daily signi?cantly decreased HbA 1c ,PPBG and postprandial insulin levels.At these dose levels,voglibose was associated with less gastrointestinal side effects and slightly less ef?cacy for postprandial glucose reduction.?2002Elsevier Science Ireland Ltd.All rights reserved.

Keywords :a -Glucosidase inhibitor;Voglibose;Acarbose;Postprandial hyperglycemia;Treatment of type 2diabetes

https://www.sodocs.net/doc/a613252247.html, /locate /diabres

1.Introduction

The importance of good blood glucose control in preventing chronic vascular complications in type 2diabetic patients has evidence-based sup-port [1].It is generally accepted that the ability to

*Corresponding author.Tel.:+66-2-419-7797;fax:+66-2-419-7792.

E -mail address :apichativ@https://www.sodocs.net/doc/a613252247.html, (A.Vichayanrat).

0168-8227/02/$-see front matter ?2002Elsevier Science Ireland Ltd.All rights reserved.PII:S 0168-8227(01)00286-8

A.Vichayanrat et al./Diabetes Research and Clinical Practice55(2002)99–103 100

achieve the best possible glycemic control both in

the fasting and postprandial states is the primary

goal in the treatment of diabetic patients.Until

recently,the signi?cance and consequences of

postprandial metabolic regulation have been ig-

nored.Ceriello reviewed the role of postprandial

hyperglycemic spikes in the pathogenesis of dia-

betic complications[2].Temelkova-Kurktschiev et

al.reported that postchallenge plasma glucose

and glycemic spikes were more strongly associated

with atherosclerosis than fasting glucose or HbA1c

[3].Several new pharmacological agents have been

developed to focus on postprandial glucose con-

trol.These include rapid-acting insulin analogues

[4],nonsulphonylurea rapid-acting insulin secreta-

gogues[5,6]and digestive enzyme inhibitors[7,8]. a-Glucosidase inhibitors which act as competitive inhibitors of intestinal a-glucosidases can delay

the digestion and subsequent absorption of carbo-

hydrate leading to attenuation of postprandial

blood glucose rises.Acarbose is the?rst a-glucosi-

dase inhibitor available for treatment.

There has been no previous direct comparative

study with voglibose,a newer a-glucosidase in-

hibitor.In this study,we evaluated the ef?cacy

and safety of voglibose in comparison with acar-

bose in type2diabetic patients whose blood

glucose levels were not well controlled by medical

and nutritional therapy.

2.Materials and methods

2.1.Patient population

The study population consisted of male and

female patients aged26–76years with an estab-

lished diagnosis of type2diabetes.They were not

taking insulin or other oral hypoglycemic agents

and had no other major medical problems.Their

blood glucose levels were not well controlled by

diet therapy,showing a1or2h postprandial

blood glucose(PPBG)level of200mg/dl or more

at the end of a4week observation period.The

stability of blood glucose was documented by a

difference of30mg/dl or less in the fasting blood

glucose(FBG)levels at the beginning and end of

the observation period.The study was carried out

in an outpatient setting.

Patients with the following conditions were ex-cluded:alcohol abuse,pregnant women or pa-tients with a desire of child bearing,patients with severe cardiac,hepatic,renal or pancreatic dis-eases,patients with chronic gastrointestinal dis-eases,patients with severe infections or severe injuries,and all patients judged by the investiga-tors to be unsuitable for the study.

Informed consent from all subjects and ap-proval from the ethnic committee of the Faculty of Medicine Siriraj Hospital,Mahidol University were obtained prior to the study.

2.2.Study design

This was a randomized crossover open compar-ative study to evaluate the ef?cacy and safety of voglibose and acarbose in type2diabetic patients whose blood glucose levels were not well con-trolled with dietary treatment.The study con-sisted of a4week observation period followed by an8week treatment period.After the observation period,patients were randomized alternately to receive either voglibose(0.2mg)or acarbose(100 mg)thrice daily with meals for8weeks.This was followed by a4week washout,a4week observa-tion and an8week treatment with the alternate drug.

Patients on oral hypoglycemic agents stopped their medications at least4weeks before the observation period.During observation,washout, and treatment periods,patients were instructed to follow medical and nutritional therapy for dia-betes mellitus.Patients who were on pharmaco-logical treatment for concomitant chronic illnesses,e.g.hypertension,dyslipidemia,etc.con-tinued to use the drugs without changing the https://www.sodocs.net/doc/a613252247.html,mencement of any new drugs or changing the dosage of drugs that may interfere with the result of the study was avoided.

After an overnight fast,FBG levels were deter-mined at the beginning and the end of the obser-vation period.If the difference was30mg/dl or less,patients were given a breakfast which con-sisted of350–400cal(carbohydrate50–55%,fat 25–30%and protein20%).PPBG levels at1and 2h and the corresponding serum insulin levels (IRI)were measured.If the results met inclusion

A.Vichayanrat et al./Diabetes Research and Clinical Practice55(2002)99–103101

criteria,patients were given the study drugs and were scheduled to be seen by the investigators every4weeks.At4and8weeks after treatment, FBG,1and2h PPBG(after breakfast with a tablet of study drug),and corresponding IRI lev-els were determined.HbA1c and lipid pro?les were determined at the end of the observation period and at the end of8weeks of treatment.Addi-tional HbA1c levels were also measured at4weeks after treatment and4weeks after stopping https://www.sodocs.net/doc/a613252247.html,plete blood count,urine analysis and blood chemistry including serum total protein, albumin,SGOT,SGPT,alkaline phosphatase, LDH,bilirubin,amylase,BUN,creatinine,cal-cium,phosphate and electrolytes were determined prior to and at8weeks after drugs treatment. Clinical data including body weight,vital signs, symptoms and signs particularly those related to the abdominal system were obtained at each study visit.All adverse drug events during the study were also recorded.

HbA1c concentration was assayed using DCA 2000analyser,based on latex immunoagglutina-tion inhibition method(Bayer corporation,nor-mal mean9SD, 5.090.35%).Serum insulin concentration was determined by radioim-munoassay using commercial kits(Diagnostics Products Corporation,USA).Lipid pro?les was performed by an enzymatic method.Blood glu-cose concentration was measured by a glucose oxidase method.Blood chemistry and urine analy-sis were performed by the central laboratory.

Compliance to drug treatment was ascertained by tablet counting at each visit.Data are ex-pressed as mean9SD.Statistical analyses was by Student’s t-test and chi-square test where appro-priate.Differences were considered statistically signi?cant at P50.05.

3.Results

3.1.Ef?cacy

Study participants included three men and27 women,with a mean age of55.0911.6years (9SD;range28–76years)and a mean body mass index(BMI)of21.193.6kg/m2(9SD; range17.8–33.3kg/m2).They had been diagnosed type2diabetes for1.792.6years(mean9SD, range0.3–13.0years).Fourteen patients had a history of taking either sulphonylurea or met-formin or both before enrollment.The mean FBG,HbA1c and IRI levels at study baseline prior to voglibose and acarbose treatment were not signi?cantly different.The effects of drugs on FBG and PPBG at4and8weeks after treatment are shown in Table1.There was no signi?cant reduction of FBG with voglibose and acarbose at 4and8weeks after treatment.The1h PPBG was signi?cantly decreased after4and8weeks of treatment for both drugs.However,2h PPBG was signi?cantly decreased only after acarbose therapy at4and8weeks.

Table1

The effects of voglibose and acarbose treatment for8weeks on FBG and PPBG levels in30patients with type2diabetes

Voglibose Acarbose

mean9SD P vs.0week mean9SD P vs.0week

157.2933.5

?4weeks FBG(mg/dl)151.9928.5

147.9935.0

145.1930.0

0weeks FBG(mg/dl)

224.9942.8

1h PPBG228.3937.4

197.5942.4

2h PPBG199.9945.6

142.7937.0ns

4weeks FBG(mg/dl)143.0926.8ns

182.7935.5B0.001

1h PPBG204.1937.60.005

166.5932.4B0.001

2h PPBG189.9950.4ns

ns

140.6935.6

ns

8weeks FBG(mg/dl)141.1937.5

0.038

206.1938.9186.6936.1B0.001

1h PPBG

B0.001

173.9944.8

ns

2h PPBG192.4951.4

A.Vichayanrat et al./Diabetes Research and Clinical Practice55(2002)99–103

102

Table2

The effects of voglibose and acarbose treatment for8weeks on HbA1c and serum insulin(IRI)levels in30patients with type2 diabetes

P vs.0week Acarbose

Voglibose P vs.0week

HbA1c(mean9SD,%)

7.0791.21

0week 6.9890.98

0.017 6.7091.04B0.001

4weeks 6.8391.11

0.036 6.5991.04B0.001

6.7991.33

8weeks

6.7291.32

4weeks off treatment0.035 6.6891.16B0.005

IRI(mean9SD,v U/ml)

14.97911.29

13.5197.52

0week fasting

48.38926.56

1h47.54931.39

46.46929.10

2h45.40926.41

ns14.46911.27

8week fasting ns

12.8898.66

1h33.14919.02B0.00131.07919.700.002

0.0631.53919.85B0.001

2h38.61923.29

Table2shows the effects of drugs therapy on HbA1c and serum IRI levels.There was a signi?-cant decrease of HbA1c concentration at4and8 weeks after both voglibose and acarbose treat-ment.A mean reduction of0.24and0.28%was observed at4and8weeks,respectively,after voglibose therapy.The corresponding?gures for acarbose treatment were0.28and0.39%.After stopping drug therapy for4weeks,HbA1c levels were still signi?cantly decreased compared with baseline,an absolute reduction of0.35and0.30% after voglibose and acarbose,respectively.

At8weeks after drugs therapy,there was no signi?cant change of fasting serum IRI levels (P\0.05).However,1and2h postprandial serum IRI levels were signi?cantly decreased after both voglibose and acarbose treatment except for the effects of voglibose at2h(P=0.06).

3.2.Safety and ad6erse drug reactions

Adverse drug events were signi?cantly more common in acarbose-treated patients(P B0.05). One or more adverse drug reactions were reported in56.7%(17/30)and90%(27/30)of patients who took voglibose and acarbose,respectively.How-ever,problematic symptoms were observed in3.3 versus43.4%of the patients who took the respec-tive drugs.Increased?atulence was reported in 56.7and90%of patients who took voglibose and acarbose,respectively,while abdominal distention was noted in10and16.7%.

The body weight was signi?cantly decreased from60.098.4to59.198.4kg and from59.99 8.4to59.198.4kg at8weeks in patients who were given voglibose and acarbose,respectively (P B0.05).However,there was no signi?cant change of body weight at4weeks.

There were no signi?cant changes of complete blood count,urine analysis,lipid pro?les and blood chemistry values over time.

4.Discussion

This study demonstrated that voglibose,an a-glucosidase inhibitor,at a dose of0.2mg3times daily,can signi?cantly lower1h PPBG levels in type2diabetic patients who were not adequately controlled with diet alone.The effects were seen both at4and8weeks after treatment.More importantly,HbA1c levels decreased.In animal models,voglibose or AO-128suppressed elevation of the blood glucose concentration after oral su-crose,maltose and starch,but not after oral glu-cose,fructose and lactose[9].In contrast to acarbose,voglibose leaves the a-amylase activity nearly unaffected.It is190–3900-fold and23–33-fold more potent than acarbose in inhibiting rat and porcine intestinal disaccharases,respectively.

A.Vichayanrat et al./Diabetes Research and Clinical Practice55(2002)99–103103

At a dose of1mg three times daily in healthy volunteers,voglibose enhanced release of glucagon-like peptide-1(GLP-1)which is an in-sulinotropic hormone[10].The rate of gastric emptying affects the ef?cacy of voglibose therapy in type2diabetic patients.However,voglibose does not alter the rate of gastric emptying[11]. Similar to our study,this paper also showed that FBG and fasting serum IRI concentrations did not change signi?cantly after voglibose therapy. Voglibose lowered daily glycemic excursion and inhibited the b-cell function,but had little effect on insulin sensitivity in NIDDM patients[12]. Compared with voglibose,acarbose treatment also lowered1h PPBG at4and8weeks,HbA1c at4and8weeks and1h postprandial serum IRI at8weeks.Acarbose,at a dosage of100mg3 times daily,seemed to be more potent and have a more prolonged action than voglibose at a dose of 0.2mg3times daily because2h PPBG at4and 8weeks and2h postprandial serum IRI concen-tration showed signi?cant decrease only after acarbose treatment.However,both drugs signi?-cantly lowered HbA1c at4and8weeks.

With regard to adverse drug events,our study demonstrated that voglibose had less drug reac-tions compared with acarbose.This might be due to the relatively lower dosage of voglibose used in this study and the less digestive enzyme inhibition of voglibose.

In conclusion,both voglibose and acarbose sig-ni?cantly decreased PPBG,HbA1c,and postpran-dial serum IRI levels without affecting FBG and fasting serum IRI concentrations in type2dia-betic patients who did not achieve adequate con-trol with diet therapy.Voglibose therapy was associated with less adverse drug reactions and slightly less postprandial glucose lowering effects. Acknowledgements

We thank the staff and fellows of the Division of Endocrinology and Metabolism,Department of Medicine,Faculty of Medicine&Siriraj Hospi-tal for referring patients for the study.The study was supported by a grant from Takeda(Thai-land),Ltd.

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英语中的比较级与最高级 详解

比较级与最高级 1.as...as 与(not) as(so)...as as...as...句型中,as的词性 第一个as是副词,用在形容词和副词的原级前,常译为“同样地”。第二个as是连词,连接与前面句子结构相同的一个句子(相同部分常省略),可译为“同..... He is as tall as his brother is (tall) . (后面的as 为连词) 只有在否定句中,第一个as才可换为so 改错: He is so tall as his brother.(X) 2.在比较状语从句中,主句和从句的句式结构一般是相同的 与as...as 句式中第二个as一样,than 也是连词。as和than这两个连词后面的从句的结构与前面的句子大部分情况下结构是相同的,相同部分可以省略。 He picked more apples than she did. 完整的表达为: He picked more apples than she picked apples. 后而的picked apples和前面相同,用did 替代。 He walked as slowly as she did.完整表达为: He walked as slowly as she walked slowly. she后面walked slowly与前面相同,用did替代。

3.谓语的替代 在as和than 引导的比较状语从句中,由于句式同前面 主句相同,为避免重复,常把主句中出现而从句中又出现的动词用do的适当形式来代替。 John speaks German as fluently as Mary does. 4.前后的比较对象应一致 不管后面连词是than 还是as,前后的比较对象应一致。The weather of Beijing is colder than Guangzhou. x than前面比较对象是“天气”,than 后面比较对象是“广州”,不能相比较。应改为: The weather of Bejing is colder than that of Guangzhou. 再如: His handwriting is as good as me. 应改为: His handwriting is as good as mine. 5.可以修饰比较级的词 常用来修饰比较级的词或短语有: Much,even,far,a little,a lot,a bit,by far,rather,any,still,a great deal等。 by far的用法: 用于强调,意为“...得多”“最最...”“显然”等,可修饰形容词或副词的比较级和最高级,通常置于其后,但是若比较级或最高级前有冠词,则可置于其前或其后。

常用兽药原粉汇总

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感官动词的用法

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的地得的用法和区分

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多媒体课件、录屏软件 八、教学设计与过程 开场白: 同学们好!今天我们一起来学习“的、地、得”的正确用法。首先我们来了解一下它们的区别。 1、相同之处:原来它们都是念轻声“de”,都是结构助词,起连接作用。 2、不同之处:在书面语中要写成三个不同的字,而且它们的搭配及用法也各不相同。 (1)怎么样的什么 (2)怎样样地干什么 (3)干得怎么样 下面我们就来学习一下它们的正确用法。 白勺“的”的结构是用“形容词或名词或代词+的+名词”来表示,而我们最常见,用得最多的还是“形容词+的+名词”的结构。 而土也“地”的用法可以用“形容词+地+动词”的结构来表示。 双人“得”是用“动词+得+形容词”的结构来表示 3、练习巩固 (1)形近区分 静静(的)河面静静(地)写字欢乐(的)山谷

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英语比较级和最高级的用法

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