Efficacy and Safety of Voglibose Compared With Acarbose in Participants With Type 2 Diabetes

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02049814
• Collaborator: (none)
• Enrollment: 494
• Locations: 18
• Arms: 2
• Actual Duration (Months): 25.7
• Patients Per Site: 27.4
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

The primary purpose of this study is to evaluate the efficacy of voglibose versus acarbose combined with metformin in participants with type 2 diabetes mellitus (T2DM) by evaluating levels of glycosylated hemoglobin.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: Metformin; Drug: Voglibose; Drug: Acarbose	Phase 4

Detailed Description

The drug being tested in this study is called voglibose. Voglibose is being tested to treat type 2 diabetes in people who have diabetes that is inadequately controlled on metformin alone. This study will look at glycemic control in people who take voglibose.

The study will enroll 494 patients. All participants will be enrolled in a 2-week screening phase and a metformin run-in phase. Eligible participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups:

• Metformin and Voglibose 0.2 mg

• Metformin and Acarbose 50 mg

All participants will be asked to take their current dose of metformin tablets and either voglibose or acarbose tablets three times a day throughout the study.

This multi-center trial will be conducted in China. The overall time to participate in this study is up to 20 weeks and participants will make 8 visits to the clinic.

Study Design

• Study Type: Interventional
• Actual Enrollment: 494 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open-label, Non-inferiority Study to Compare the Efficacy and Safety of Voglibose and Acarbose in Patients With Type 2 Diabetes Mellitus With Poor Control of Metformin
• Actual Study Start Date: May 9, 2014
• Actual Primary Completion Date: Jun 1, 2016
• Actual Study Completion Date: Jun 28, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Metformin + Voglibose 0.2 mg Metformin tablets, at the maximum tolerated dose ≥1000 mg/day, orally, for 12 weeks, in addition to voglibose 0.2 mg, tablets, orally, three times daily, for Weeks 1 and 2, followed by voglibose 0.3 mg, tablets, orally, three times daily, Weeks 3 through 12.	Drug: Metformin; Metformin tablets; Other Names: Glucophage ; Drug: Voglibose; Voglibose tablets; Other Names: Basen
Active Comparator: Metformin + Acarbose 50 mg Metformin tablets, at the maximum tolerated dose ≥1000 mg/day, orally, for 12 weeks, in addition to acarbose 50 mg, tablets, orally, three times daily, Weeks 1 and 2, then acarbose 100 mg, tablets, orally, three times daily, Weeks 3 through 12.	Drug: Metformin; Metformin tablets; Other Names: Glucophage ; Drug: Acarbose; Acarbose tablets; Other Names: Glucobay, Precose, Prandase

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 12 [Baseline, Week 12]

   The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 12 or final visit relative to baseline.

Secondary Outcome Measures

1. Change From Baseline in HbA1c at Week 6 [Baseline and Week 6]

   The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 6 relative to baseline.

2. Change From Baseline in Fasting Blood Glucose Over Time [Baseline, Weeks 6 and 12]

   The change between the fasting blood glucose value collected at weeks 6 and 12 or final visit relative to baseline.

3. Change From Baseline in Postprandial Plasma Glucose (PPG) Over Time [1 and 2 hours after meal at Baseline, Weeks 6 and 12]

   The change between the value of glucose after 1 and 2 hours of meal, measured by the meal tolerance test collected at Weeks 6 and 12 or relative to baseline.

4. Change From Baseline in Fasting Insulin at Week 12 [Baseline, Week 12]

   The change between the fasting insulin value collected at week 12 or final visit relative to baseline.

5. Change From Baseline in Postprandial Serum Insulin at Week 12 [1 and 2 hours after meal at Baseline and Week 12]

   The change from Baseline in postprandial serum insulin, after 1 and 2 hours of meal collected at Week 12 relative to baseline.

6. Change From Baseline in Fasting Glucagon at Week 12 [Baseline, Week 12]

   The change between the fasting glucagon value collected at week 12 or final visit relative to baseline.

7. Change From Baseline in Postprandial Serum Glucagon at Week 12 [1 and 2 hours after meal at Baseline and Week 12]

   The change from Baseline in postprandial serum glucagon, after 1 and 2 hours of meal collected at Week 12 relative to baseline.

8. Change From Baseline in Calculated Homeostatic Model Assessment Insulin Resistance (HOMA IR) at Week 12 [Baseline, Week 12]

   The change between the value of HOMA-IR collected at Week 12 and HOMA-IR collected at Baseline. HOMA IR measures insulin resistance based on fasting glucose and insulin measurements: HOMA IR = fasting plasma insulin (µIU/mL) * fasting plasma glucose (mmol/L) / 22.5. A higher number indicates a greater insulin resistance.

9. Change From Baseline in Insulin Homeostatic Model Assessment Beta Cell Function (HOMA β) at Week 12 [Baseline, Week 12]

   The change between the value of HOMA-beta cell function collected at Week 12 and HOMA-beta cell function collected at Baseline. The homeostatic model assessment estimates steady state beta cell function as a percentage of a normal reference population (%B). HOMA %B = 20 * insulin (µIU/mL) / fasting plasma glucose (mmol/L) - 3.5.

10. Change From Baseline in Body Weight Over Time [Baseline, Weeks 2, 6 and 12]

    The change between body weight at weeks 2, 6 and 12 or relative to baseline.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Has a historical diagnosis of type 2 diabetes mellitus (T2DM) for at least 6 months prior to the screening visit (V1).

2. Is male or female and aged from 18 to 75 years, inclusively.

3. Has a body mass index (BMI) between 20 and 45 kg/m^2, inclusively.

4. Is experiencing inadequate glycemic control with a glycosylated hemoglobin (HbA1c) concentration between 7.0% and 10.0%, inclusively.

5. Has been treated with Metformin for at least 3 months and at a stable dose (≥1000 mg/day) for at least 8 weeks prior to Screening, unless there is documentation that the participant's current dose is his or her maximum tolerated dose (MTD) and MTD is ≤1000 mg/day.

6. Keeps constant body weight with fluctuation range no more than 10% over for at least 3 months before screening.

7. Hemoglobin levels of the participant are ≥12 g/dL (≥120 g/L) in male and≥ 10 g/dL (≥100 g/L) in female at screening visit.

8. Male serum creatinine <1.5 mg/dL and female serum creatinine <1.4 mg/dL, or estimated glomerular filtration rate (eGFR) >60 ml/min/1.73m^2 based on calculation using the Modification of Diet in Renal Disease (MDRD) approximation at Screening.

9. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.

10. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written informed consent form and any required privacy authorization prior to the initiation of any study procedures.

Exclusion Criteria:

1. Type 1 diabetes mellitus.

2. Has received insulin, voglibose, acarbose or other oral hypoglycemic drugs (except Metformin) for accumulative total of more than 7 days within the latest 3 months prior to Visit 1.

3. Has a history of cardiovascular disease: acute myocardial infarction, class III or IV heart failure, or cerebrovascular accident (stroke) within the latest 3 months prior to Visit 1.

4. The participant's liver function is damaged and has a significant clinical sign or symptom of hepatopathy, acute or chronic hepatitis, or the value of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) is 3 times more than the upper limit of normal level at Visit 1.

5. Has an active proliferative retinopathy or macular degeneration that need to have an urgent treatment in the opinion of investigators.

6. Has a frequent attack of hypoglycemia or loses consciousness due to hypoglycemia in the opinion of investigators.

7. Has one or more times ketoacidosis or hyperosmotic status/coma.

8. Is receiving long-term (>14days) systemic glucocorticoid treatment (except the medicine: local, intraocular, inhalation or via the nose) or has received such treatment for 4 weeks at Visit 1.

9. Has a hematopathy (e.g. hemolytic anemia, drepanocytosis) that may interfere with the HbA1c test.

10. Has other liabilities (e.g. drug abuse, alcoholism or mental disorder) that may hinder the participant to follow and complete the study.

11. Has participated in another clinical study within the past 90 days or has received any investigational compound within 30 days prior to randomization.

12. Is unsuitable for this study in the opinion of investigators.

13. Has a disease need to use other taboo or caution drugs that is not listed in this study.

14. If female, is pregnant or lactating or intending to become pregnant before, during, or within 30 days after participating in this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Hefei	Anhui	China
2		Maanshan	Anhui	China
3		Beijing	Beijing	China
4		Guangzhou	Guangdong	China
5		Shenzhen	Guangdong	China
6		Taishan	Guangdong	China
7		Zhuzhou	Hunan	China
8		Nanjing	Jiangsu	China
9		Xuzhou	Jiangsu	China
10		Changchun	Jilin	China
11		Jilin	Jilin	China
12		Shenyang	Liaoning	China
13		Qingdao	Shandong	China
14		Shanghai	Shanghai	China
15		Yan An	Shanxi	China
16		Yanan	Shanxi	China
17		Tianjin	Tianjin	China
18		Wenzhou	Zhejiang	China

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Medical Director, Clinical Science, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT02049814
• Other Study ID Numbers: BASCN1201; U1111-1147-3393; VOG-P4-001
• First Posted: Jan 30, 2014
• Last Update Posted: Mar 13, 2019
• Last Verified: Feb 1, 2019

• Keywords provided by Takeda: Drug therapy
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Metformin; Acarbose; Voglibose

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 22 investigative sites in China from 09 May 2014 to 28 June 2016.
Pre-assignment Detail	Participants with a diagnosis of type 2 diabetes mellitus (T2DM) were enrolled in 1:1 to receive voglibose combined with metformin or acarbose combined with metformin.

Arm/Group Title	Metformin + Voglibose 0.2 mg	Metformin + Acarbose 50 mg
Arm/Group Description	Metformin tablets, at the maximum tolerated dose ≥1000 mg/day, orally, for 12 weeks, in addition to voglibose 0.2 mg, tablets, orally, three times daily, for Weeks 1 and 2, followed by voglibose 0.3 mg, tablets, orally, three times daily, Weeks 3 through 12.	Metformin tablets, at the maximum tolerated dose ≥1000 mg/day, orally, for 12 weeks, in addition to acarbose 50 mg, tablets, orally, three times daily, Weeks 1 and 2, then acarbose 100 mg, tablets, orally, three times daily, Weeks 3 through 12.
Period Title: Overall Study
STARTED	248	246
Safety Set	248	245
COMPLETED	219	219
NOT COMPLETED	29	27

Baseline Characteristics

Arm/Group Title	Metformin + Voglibose 0.2 mg	Metformin + Acarbose 50 mg	Total
Arm/Group Description	Metformin tablets, at the maximum tolerated dose ≥1000 mg/day, orally, for 12 weeks, in addition to voglibose 0.2 mg, tablets, orally, three times daily, for Weeks 1 and 2, followed by voglibose 0.3 mg, tablets, orally, three times daily, Weeks 3 through 12.	Metformin tablets, at the maximum tolerated dose ≥1000 mg/day, orally, for 12 weeks, in addition to acarbose 50 mg, tablets, orally, three times daily, Weeks 1 and 2, then acarbose 100 mg, tablets, orally, three times daily, Weeks 3 through 12.	Total of all reporting groups
Overall Participants	236	233	469
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.41 (9.239)	54.82 (9.386)	54.62 (9.305)
Sex: Female, Male (Count of Participants)
Female	114 48.3%	108 46.4%	222 47.3%
Male	122 51.7%	125 53.6%	247 52.7%
Race/Ethnicity, Customized (participants) [Number]
Ethnic Chinese	236 100%	233 100%	469 100%
Region of Enrollment (participants) [Number]
China	236 100%	233 100%	469 100%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	164.8 (8.05)	165.2 (8.07)	165.0 (8.05)
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	26.4 (3.27)	26.4 (3.63)	26.4 (3.45)
Baseline Systolic Blood Pressure (SBP) (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	126.2 (12.22)	127.5 (12.69)	126.8 (12.46)
Baseline Diastolic Blood Pressure (DBP) (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	76.5 (7.69)	77.7 (8.28)	77.1 (8.00)
Baseline Pulse (bpm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [bpm]	74.3 (7.73)	75.4 (8.47)	74.9 (8.12)
Baseline Temperature (°C) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [°C]	36.3 (0.27)	36.4 (0.25)	36.3 (0.26)
Baseline Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	71.6 (11.68)	72.0 (12.09)	71.8 (11.87)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 12
Description	The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 12 or final visit relative to baseline.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Per Protocol Set (PPS) is a subset of FAS, including participants who completed treatment as was prescribed in protocol and had no important protocol deviation.

Arm/Group Title	Metformin + Voglibose 0.2 mg	Metformin + Acarbose 50 mg
Arm/Group Description	Metformin tablets, at the maximum tolerated dose ≥1000 mg/day, orally, for 12 weeks, in addition to voglibose 0.2 mg, tablets, orally, three times daily, for Weeks 1 and 2, followed by voglibose 0.3 mg, tablets, orally, three times daily, Weeks 3 through 12.	Metformin tablets, at the maximum tolerated dose ≥1000 mg/day, orally, for 12 weeks, in addition to acarbose 50 mg, tablets, orally, three times daily, Weeks 1 and 2, then acarbose 100 mg, tablets, orally, three times daily, Weeks 3 through 12.
Measure Participants	156	156
Least Squares Mean (Standard Error) [percentage of glycated hemoglobin]	-0.6982 (0.0742)	-0.9335 (0.0764)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Metformin + Voglibose 0.2 mg, Metformin + Acarbose 50 mg
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	If the upper limit of 95% CI of Least Square Mean (LS mean) of HbA1C Changes was less than 0.4%, it was considered that the non-inferiority was established.
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Paired t-test
	Comments

2. Secondary Outcome

Title	Change From Baseline in HbA1c at Week 6
Description	The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 6 relative to baseline.
Time Frame	Baseline and Week 6

Outcome Measure Data

Analysis Population Description

PPS is a subset of FAS, including participants who completed treatment as was prescribed in protocol and had no important protocol deviation.

Arm/Group Title	Metformin + Voglibose 0.2 mg	Metformin + Acarbose 50 mg
Arm/Group Description	Metformin tablets, at the maximum tolerated dose ≥1000 mg/day, orally, for 12 weeks, in addition to voglibose 0.2 mg, tablets, orally, three times daily, for Weeks 1 and 2, followed by voglibose 0.3 mg, tablets, orally, three times daily, Weeks 3 through 12.	Metformin tablets, at the maximum tolerated dose ≥1000 mg/day, orally, for 12 weeks, in addition to acarbose 50 mg, tablets, orally, three times daily, Weeks 1 and 2, then acarbose 100 mg, tablets, orally, three times daily, Weeks 3 through 12.
Measure Participants	156	156
Least Squares Mean (Standard Error) [percentage of glycated hemoglobin]	-0.4765 (0.0605)	-0.631 (0.0623)

3. Secondary Outcome

Title	Change From Baseline in Fasting Blood Glucose Over Time
Description	The change between the fasting blood glucose value collected at weeks 6 and 12 or final visit relative to baseline.
Time Frame	Baseline, Weeks 6 and 12

Outcome Measure Data

Analysis Population Description

PPS is a subset of FAS, including participants who completed treatment as was prescribed in protocol and had no important protocol deviation.

Arm/Group Title	Metformin + Voglibose 0.2 mg	Metformin + Acarbose 50 mg
Arm/Group Description	Metformin tablets, at the maximum tolerated dose ≥1000 mg/day, orally, for 12 weeks, in addition to voglibose 0.2 mg, tablets, orally, three times daily, for Weeks 1 and 2, followed by voglibose 0.3 mg, tablets, orally, three times daily, Weeks 3 through 12.	Metformin tablets, at the maximum tolerated dose ≥1000 mg/day, orally, for 12 weeks, in addition to acarbose 50 mg, tablets, orally, three times daily, Weeks 1 and 2, then acarbose 100 mg, tablets, orally, three times daily, Weeks 3 through 12.
Measure Participants	156	156
Change at Week 6	-0.4234 (0.1397)	-0.8851 (0.1438)
Change at Week 12	-0.5041 (0.1398)	-0.8029 (0.1439)

4. Secondary Outcome

Title	Change From Baseline in Postprandial Plasma Glucose (PPG) Over Time
Description	The change between the value of glucose after 1 and 2 hours of meal, measured by the meal tolerance test collected at Weeks 6 and 12 or relative to baseline.
Time Frame	1 and 2 hours after meal at Baseline, Weeks 6 and 12

Outcome Measure Data

Analysis Population Description

PPS is a subset of FAS, including participants who completed treatment as was prescribed in protocol and had no important protocol deviation.

Arm/Group Title	Metformin + Voglibose 0.2 mg	Metformin + Acarbose 50 mg
Arm/Group Description	Metformin tablets, at the maximum tolerated dose ≥1000 mg/day, orally, for 12 weeks, in addition to voglibose 0.2 mg, tablets, orally, three times daily, for Weeks 1 and 2, followed by voglibose 0.3 mg, tablets, orally, three times daily, Weeks 3 through 12.	Metformin tablets, at the maximum tolerated dose ≥1000 mg/day, orally, for 12 weeks, in addition to acarbose 50 mg, tablets, orally, three times daily, Weeks 1 and 2, then acarbose 100 mg, tablets, orally, three times daily, Weeks 3 through 12.
Measure Participants	156	156
Change at Week 6 (1 hour PPG)	-2.5149 (0.2308)	-3.8557 (0.2377)
Change at Week 12 (1 hour PPG)	-2.1187 (0.2376)	-2.1187 (0.2376)
Change at Week 6 (2 hour PPG)	-2.7461 (0.2553)	-4.0015 (0.2624)
Change at Week 12 (2 hour PPG)	-2.6099 (0.2632)	-3.2347 (0.2705)

5. Secondary Outcome

Title	Change From Baseline in Fasting Insulin at Week 12
Description	The change between the fasting insulin value collected at week 12 or final visit relative to baseline.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

PPS is a subset of FAS, including participants who completed treatment as was prescribed in protocol and had no important protocol deviation.

Arm/Group Title	Metformin + Voglibose 0.2 mg	Metformin + Acarbose 50 mg
Arm/Group Description	Metformin tablets, at the maximum tolerated dose ≥1000 mg/day, orally, for 12 weeks, in addition to voglibose 0.2 mg, tablets, orally, three times daily, for Weeks 1 and 2, followed by voglibose 0.3 mg, tablets, orally, three times daily, Weeks 3 through 12.	Metformin tablets, at the maximum tolerated dose ≥1000 mg/day, orally, for 12 weeks, in addition to acarbose 50 mg, tablets, orally, three times daily, Weeks 1 and 2, then acarbose 100 mg, tablets, orally, three times daily, Weeks 3 through 12.
Measure Participants	156	156
Least Squares Mean (Standard Error) [μU/dL]	0.0319 (1.1481)	2.4169 (1.1959)

6. Secondary Outcome

Title	Change From Baseline in Postprandial Serum Insulin at Week 12
Description	The change from Baseline in postprandial serum insulin, after 1 and 2 hours of meal collected at Week 12 relative to baseline.
Time Frame	1 and 2 hours after meal at Baseline and Week 12

Outcome Measure Data

Analysis Population Description

PPS is a subset of FAS, including participants who completed treatment as was prescribed in protocol and had no important protocol deviation.

Arm/Group Title	Metformin + Voglibose 0.2 mg	Metformin + Acarbose 50 mg
Arm/Group Description	Metformin tablets, at the maximum tolerated dose ≥1000 mg/day, orally, for 12 weeks, in addition to voglibose 0.2 mg, tablets, orally, three times daily, for Weeks 1 and 2, followed by voglibose 0.3 mg, tablets, orally, three times daily, Weeks 3 through 12.	Metformin tablets, at the maximum tolerated dose ≥1000 mg/day, orally, for 12 weeks, in addition to acarbose 50 mg, tablets, orally, three times daily, Weeks 1 and 2, then acarbose 100 mg, tablets, orally, three times daily, Weeks 3 through 12.
Measure Participants	156	156
Change at Week 12 (1 hour)	-0.3435 (2.2504)	-1.44 (2.341)
Change at Week 12 (2 hours)	3.2972 (3.0059)	-0.1526 (3.1145)

7. Secondary Outcome

Title	Change From Baseline in Fasting Glucagon at Week 12
Description	The change between the fasting glucagon value collected at week 12 or final visit relative to baseline.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

PPS is a subset of FAS, including participants who completed treatment as was prescribed in protocol and had no important protocol deviation.

Arm/Group Title	Metformin + Voglibose 0.2 mg	Metformin + Acarbose 50 mg
Arm/Group Description	Metformin tablets, at the maximum tolerated dose ≥1000 mg/day, orally, for 12 weeks, in addition to voglibose 0.2 mg, tablets, orally, three times daily, for Weeks 1 and 2, followed by voglibose 0.3 mg, tablets, orally, three times daily, Weeks 3 through 12.	Metformin tablets, at the maximum tolerated dose ≥1000 mg/day, orally, for 12 weeks, in addition to acarbose 50 mg, tablets, orally, three times daily, Weeks 1 and 2, then acarbose 100 mg, tablets, orally, three times daily, Weeks 3 through 12.
Measure Participants	156	156
Least Squares Mean (Standard Error) [pg/mL]	5.7543 (6.0009)	11.4541 (6.2524)

8. Secondary Outcome

Title	Change From Baseline in Postprandial Serum Glucagon at Week 12
Description	The change from Baseline in postprandial serum glucagon, after 1 and 2 hours of meal collected at Week 12 relative to baseline.
Time Frame	1 and 2 hours after meal at Baseline and Week 12

Outcome Measure Data

Analysis Population Description

PPS is a subset of FAS, including participants who completed treatment as was prescribed in protocol and had no important protocol deviation.

Arm/Group Title	Metformin + Voglibose 0.2 mg	Metformin + Acarbose 50 mg
Arm/Group Description	Metformin tablets, at the maximum tolerated dose ≥1000 mg/day, orally, for 12 weeks, in addition to voglibose 0.2 mg, tablets, orally, three times daily, for Weeks 1 and 2, followed by voglibose 0.3 mg, tablets, orally, three times daily, Weeks 3 through 12.	Metformin tablets, at the maximum tolerated dose ≥1000 mg/day, orally, for 12 weeks, in addition to acarbose 50 mg, tablets, orally, three times daily, Weeks 1 and 2, then acarbose 100 mg, tablets, orally, three times daily, Weeks 3 through 12.
Measure Participants	156	156
Change at Week 12 (1 hour)	20.4409 (5.683)	15.69 (5.9068)
Change at Week 12 (2 hours)	34.8518 (6.41)	13.0188 (6.6143)

9. Secondary Outcome

Title	Change From Baseline in Calculated Homeostatic Model Assessment Insulin Resistance (HOMA IR) at Week 12
Description	The change between the value of HOMA-IR collected at Week 12 and HOMA-IR collected at Baseline. HOMA IR measures insulin resistance based on fasting glucose and insulin measurements: HOMA IR = fasting plasma insulin (µIU/mL) * fasting plasma glucose (mmol/L) / 22.5. A higher number indicates a greater insulin resistance.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

PPS is a subset of FAS, including participants who completed treatment as was prescribed in protocol and had no important protocol deviation.

Arm/Group Title	Metformin + Voglibose 0.2 mg	Metformin + Acarbose 50 mg
Arm/Group Description	Metformin tablets, at the maximum tolerated dose ≥1000 mg/day, orally, for 12 weeks, in addition to voglibose 0.2 mg, tablets, orally, three times daily, for Weeks 1 and 2, followed by voglibose 0.3 mg, tablets, orally, three times daily, Weeks 3 through 12.	Metformin tablets, at the maximum tolerated dose ≥1000 mg/day, orally, for 12 weeks, in addition to acarbose 50 mg, tablets, orally, three times daily, Weeks 1 and 2, then acarbose 100 mg, tablets, orally, three times daily, Weeks 3 through 12.
Measure Participants	156	156
Least Squares Mean (Standard Error) [Insulin resistance]	-0.366 (0.5389)	0.4983 (0.5596)

10. Secondary Outcome

Title	Change From Baseline in Insulin Homeostatic Model Assessment Beta Cell Function (HOMA β) at Week 12
Description	The change between the value of HOMA-beta cell function collected at Week 12 and HOMA-beta cell function collected at Baseline. The homeostatic model assessment estimates steady state beta cell function as a percentage of a normal reference population (%B). HOMA %B = 20 * insulin (µIU/mL) / fasting plasma glucose (mmol/L) - 3.5.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

PPS is a subset of FAS, including participants who completed treatment as was prescribed in protocol and had no important protocol deviation.

Arm/Group Title	Metformin + Voglibose 0.2 mg	Metformin + Acarbose 50 mg
Arm/Group Description	Metformin tablets, at the maximum tolerated dose ≥1000 mg/day, orally, for 12 weeks, in addition to voglibose 0.2 mg, tablets, orally, three times daily, for Weeks 1 and 2, followed by voglibose 0.3 mg, tablets, orally, three times daily, Weeks 3 through 12.	Metformin tablets, at the maximum tolerated dose ≥1000 mg/day, orally, for 12 weeks, in addition to acarbose 50 mg, tablets, orally, three times daily, Weeks 1 and 2, then acarbose 100 mg, tablets, orally, three times daily, Weeks 3 through 12.
Measure Participants	156	156
Least Squares Mean (Standard Error) [Percentage beta cell function]	15.3149 (5.4717)	28.1739 (5.7253)

11. Secondary Outcome

Title	Change From Baseline in Body Weight Over Time
Description	The change between body weight at weeks 2, 6 and 12 or relative to baseline.
Time Frame	Baseline, Weeks 2, 6 and 12

Outcome Measure Data

Analysis Population Description

PPS is a subset of FAS, including participants who completed treatment as was prescribed in protocol and had no important protocol deviation.

Arm/Group Title	Metformin + Voglibose 0.2 mg	Metformin + Acarbose 50 mg
Arm/Group Description	Metformin tablets, at the maximum tolerated dose ≥1000 mg/day, orally, for 12 weeks, in addition to voglibose 0.2 mg, tablets, orally, three times daily, for Weeks 1 and 2, followed by voglibose 0.3 mg, tablets, orally, three times daily, Weeks 3 through 12.	Metformin tablets, at the maximum tolerated dose ≥1000 mg/day, orally, for 12 weeks, in addition to acarbose 50 mg, tablets, orally, three times daily, Weeks 1 and 2, then acarbose 100 mg, tablets, orally, three times daily, Weeks 3 through 12.
Measure Participants	156	156
Change at Week 2	-0.016 (0.1661)	-0.1731 (0.1725)
Change at Week 6	-0.6315 (0.1412)	-0.7975 (0.1466)
Change at Week 12	-1.1563 (0.1878)	-1.4394 (0.1951)

Adverse Events

Time Frame	Up to Week 14
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety set included all randomized participants who received at least one dose of study treatment and had at least one subsequent safety assessment.
Arm/Group Title	Metformin + Voglibose 0.2 mg		Metformin + Acarbose 50 mg
Arm/Group Description	Metformin tablets, at the maximum tolerated dose ≥1000 mg/day, orally, for 12 weeks, in addition to voglibose 0.2 mg, tablets, orally, three times daily, for Weeks 1 and 2, followed by voglibose 0.3 mg, tablets, orally, three times daily, Weeks 3 through 12.		Metformin tablets, at the maximum tolerated dose ≥1000 mg/day, orally, for 12 weeks, in addition to acarbose 50 mg, tablets, orally, three times daily, Weeks 1 and 2, then acarbose 100 mg, tablets, orally, three times daily, Weeks 3 through 12.
All Cause Mortality
	Metformin + Voglibose 0.2 mg		Metformin + Acarbose 50 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Metformin + Voglibose 0.2 mg		Metformin + Acarbose 50 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/248 (1.2%)		5/245 (2%)
Cardiac disorders
Acute coronary syndrome	0/248 (0%)		1/245 (0.4%)
Ear and labyrinth disorders
Sudden hearing loss	1/248 (0.4%)		0/245 (0%)
General disorders
Local swelling	0/248 (0%)		1/245 (0.4%)
Investigations
ALT increased	0/248 (0%)		1/245 (0.4%)
Abnormal liver function test	1/248 (0.4%)		0/245 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cerebral hemangioma	0/248 (0%)		1/245 (0.4%)
Hepatic tumor	0/248 (0%)		1/245 (0.4%)
Nervous system disorders
Cerebral ischemia	1/248 (0.4%)		0/245 (0%)
Other (Not Including Serious) Adverse Events
	Metformin + Voglibose 0.2 mg		Metformin + Acarbose 50 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/248 (15.3%)		41/245 (16.7%)
Gastrointestinal disorders
Flatulence	23/248 (9.3%)		41/245 (16.7%)
Infections and infestations
Urinary tract infection	15/248 (6%)		9/245 (3.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.