Trial Outcomes & Findings for Efficacy and Safety of Voglibose Compared With Acarbose in Participants With Type 2 Diabetes (NCT NCT02049814)

NCT ID: NCT02049814

Last Updated: 2019-03-13

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 494 participants
• Primary outcome timeframe: Baseline, Week 12
• Results posted on: 2019-03-13

Participant Flow

Participants took part in the study at 22 investigative sites in China from 09 May 2014 to 28 June 2016.

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.

Participant milestones

Measure	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.	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.
Overall Study STARTED	248	246
Overall Study Safety Set	248	245
Overall Study COMPLETED	219	219
Overall Study NOT COMPLETED	29	27

Reasons for withdrawal

Measure	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.	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.
Overall Study Reason not Specified	4	3
Overall Study Pregnancy	1	0
Overall Study Lost to Follow-up	2	3
Overall Study Serious Protocol Violation	5	7
Overall Study Study Termination	0	1
Overall Study Pretreatment event/Adverse Event (AE)	8	5
Overall Study Voluntary withdrawal	9	8

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Metformin + Voglibose 0.2 mg n=236 Participants 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 + Acarbose 50 mg n=233 Participants 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 n=469 Participants Total of all reporting groups
Age, Continuous	54.41 years STANDARD_DEVIATION 9.239 • n=5 Participants	54.82 years STANDARD_DEVIATION 9.386 • n=7 Participants	54.62 years STANDARD_DEVIATION 9.305 • n=5 Participants
Sex: Female, Male Female	114 Participants n=5 Participants	108 Participants n=7 Participants	222 Participants n=5 Participants
Sex: Female, Male Male	122 Participants n=5 Participants	125 Participants n=7 Participants	247 Participants n=5 Participants
Race/Ethnicity, Customized Ethnic Chinese	236 participants n=5 Participants	233 participants n=7 Participants	469 participants n=5 Participants
Region of Enrollment China	236 participants n=5 Participants	233 participants n=7 Participants	469 participants n=5 Participants
Height	164.8 cm STANDARD_DEVIATION 8.05 • n=5 Participants	165.2 cm STANDARD_DEVIATION 8.07 • n=7 Participants	165.0 cm STANDARD_DEVIATION 8.05 • n=5 Participants
Body Mass Index	26.4 kg/m^2 STANDARD_DEVIATION 3.27 • n=5 Participants	26.4 kg/m^2 STANDARD_DEVIATION 3.63 • n=7 Participants	26.4 kg/m^2 STANDARD_DEVIATION 3.45 • n=5 Participants
Baseline Systolic Blood Pressure (SBP)	126.2 mmHg STANDARD_DEVIATION 12.22 • n=5 Participants	127.5 mmHg STANDARD_DEVIATION 12.69 • n=7 Participants	126.8 mmHg STANDARD_DEVIATION 12.46 • n=5 Participants
Baseline Diastolic Blood Pressure (DBP)	76.5 mmHg STANDARD_DEVIATION 7.69 • n=5 Participants	77.7 mmHg STANDARD_DEVIATION 8.28 • n=7 Participants	77.1 mmHg STANDARD_DEVIATION 8.00 • n=5 Participants
Baseline Pulse	74.3 bpm STANDARD_DEVIATION 7.73 • n=5 Participants	75.4 bpm STANDARD_DEVIATION 8.47 • n=7 Participants	74.9 bpm STANDARD_DEVIATION 8.12 • n=5 Participants
Baseline Temperature	36.3 °C STANDARD_DEVIATION 0.27 • n=5 Participants	36.4 °C STANDARD_DEVIATION 0.25 • n=7 Participants	36.3 °C STANDARD_DEVIATION 0.26 • n=5 Participants
Baseline Weight	71.6 kg STANDARD_DEVIATION 11.68 • n=5 Participants	72.0 kg STANDARD_DEVIATION 12.09 • n=7 Participants	71.8 kg STANDARD_DEVIATION 11.87 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: 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.

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.

Outcome measures

Measure	Metformin + Voglibose 0.2 mg n=156 Participants 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 + Acarbose 50 mg n=156 Participants 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.
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 12	-0.6982 percentage of glycated hemoglobin Standard Error 0.0742	-0.9335 percentage of glycated hemoglobin Standard Error 0.0764

SECONDARY outcome

Timeframe: Baseline and Week 6

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

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.

Outcome measures

Measure	Metformin + Voglibose 0.2 mg n=156 Participants 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 + Acarbose 50 mg n=156 Participants 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.
Change From Baseline in HbA1c at Week 6	-0.4765 percentage of glycated hemoglobin Standard Error 0.0605	-0.631 percentage of glycated hemoglobin Standard Error 0.0623

SECONDARY outcome

Timeframe: Baseline, Weeks 6 and 12

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

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

Outcome measures

Measure	Metformin + Voglibose 0.2 mg n=156 Participants 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 + Acarbose 50 mg n=156 Participants 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.
Change From Baseline in Fasting Blood Glucose Over Time Change at Week 6	-0.4234 mmol/L Standard Error 0.1397	-0.8851 mmol/L Standard Error 0.1438
Change From Baseline in Fasting Blood Glucose Over Time Change at Week 12	-0.5041 mmol/L Standard Error 0.1398	-0.8029 mmol/L Standard Error 0.1439

SECONDARY outcome

Timeframe: 1 and 2 hours after meal at Baseline, Weeks 6 and 12

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

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.

Outcome measures

Measure	Metformin + Voglibose 0.2 mg n=156 Participants 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 + Acarbose 50 mg n=156 Participants 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.
Change From Baseline in Postprandial Plasma Glucose (PPG) Over Time Change at Week 6 (1 hour PPG)	-2.5149 mmol/L Standard Error 0.2308	-3.8557 mmol/L Standard Error 0.2377
Change From Baseline in Postprandial Plasma Glucose (PPG) Over Time Change at Week 12 (1 hour PPG)	-2.1187 mmol/L Standard Error 0.2376	-2.1187 mmol/L Standard Error 0.2376
Change From Baseline in Postprandial Plasma Glucose (PPG) Over Time Change at Week 6 (2 hour PPG)	-2.7461 mmol/L Standard Error 0.2553	-4.0015 mmol/L Standard Error 0.2624
Change From Baseline in Postprandial Plasma Glucose (PPG) Over Time Change at Week 12 (2 hour PPG)	-2.6099 mmol/L Standard Error 0.2632	-3.2347 mmol/L Standard Error 0.2705

SECONDARY outcome

Timeframe: Baseline, Week 12

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

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

Outcome measures

Measure	Metformin + Voglibose 0.2 mg n=156 Participants 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 + Acarbose 50 mg n=156 Participants 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.
Change From Baseline in Fasting Insulin at Week 12	0.0319 μU/dL Standard Error 1.1481	2.4169 μU/dL Standard Error 1.1959

SECONDARY outcome

Timeframe: 1 and 2 hours after meal at Baseline and Week 12

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

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

Outcome measures

Measure	Metformin + Voglibose 0.2 mg n=156 Participants 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 + Acarbose 50 mg n=156 Participants 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.
Change From Baseline in Postprandial Serum Insulin at Week 12 Change at Week 12 (1 hour)	-0.3435 μU/dL Standard Error 2.2504	-1.44 μU/dL Standard Error 2.341
Change From Baseline in Postprandial Serum Insulin at Week 12 Change at Week 12 (2 hours)	3.2972 μU/dL Standard Error 3.0059	-0.1526 μU/dL Standard Error 3.1145

SECONDARY outcome

Timeframe: Baseline, Week 12

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

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

Outcome measures

Measure	Metformin + Voglibose 0.2 mg n=156 Participants 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 + Acarbose 50 mg n=156 Participants 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.
Change From Baseline in Fasting Glucagon at Week 12	5.7543 pg/mL Standard Error 6.0009	11.4541 pg/mL Standard Error 6.2524

SECONDARY outcome

Timeframe: 1 and 2 hours after meal at Baseline and Week 12

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

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

Outcome measures

Measure	Metformin + Voglibose 0.2 mg n=156 Participants 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 + Acarbose 50 mg n=156 Participants 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.
Change From Baseline in Postprandial Serum Glucagon at Week 12 Change at Week 12 (1 hour)	20.4409 pg/mL Standard Error 5.683	15.69 pg/mL Standard Error 5.9068
Change From Baseline in Postprandial Serum Glucagon at Week 12 Change at Week 12 (2 hours)	34.8518 pg/mL Standard Error 6.41	13.0188 pg/mL Standard Error 6.6143

SECONDARY outcome

Timeframe: Baseline, Week 12

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

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.

Outcome measures

Measure	Metformin + Voglibose 0.2 mg n=156 Participants 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 + Acarbose 50 mg n=156 Participants 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.
Change From Baseline in Calculated Homeostatic Model Assessment Insulin Resistance (HOMA IR) at Week 12	-0.366 Insulin resistance Standard Error 0.5389	0.4983 Insulin resistance Standard Error 0.5596

SECONDARY outcome

Timeframe: Baseline, Week 12

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

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.

Outcome measures

Measure	Metformin + Voglibose 0.2 mg n=156 Participants 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 + Acarbose 50 mg n=156 Participants 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.
Change From Baseline in Insulin Homeostatic Model Assessment Beta Cell Function (HOMA β) at Week 12	15.3149 Percentage beta cell function Standard Error 5.4717	28.1739 Percentage beta cell function Standard Error 5.7253

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 6 and 12

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

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

Outcome measures

Measure	Metformin + Voglibose 0.2 mg n=156 Participants 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 + Acarbose 50 mg n=156 Participants 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.
Change From Baseline in Body Weight Over Time Change at Week 2	-0.016 kg Standard Error 0.1661	-0.1731 kg Standard Error 0.1725
Change From Baseline in Body Weight Over Time Change at Week 6	-0.6315 kg Standard Error 0.1412	-0.7975 kg Standard Error 0.1466
Change From Baseline in Body Weight Over Time Change at Week 12	-1.1563 kg Standard Error 0.1878	-1.4394 kg Standard Error 0.1951

Adverse Events

Metformin + Voglibose 0.2 mg

Serious events: 3 serious events

Other events: 38 other events

Deaths: 0 deaths

Metformin + Acarbose 50 mg

Serious events: 5 serious events

Other events: 41 other events

Deaths: 0 deaths

Serious adverse events

Measure	Metformin + Voglibose 0.2 mg n=248 participants at risk 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 + Acarbose 50 mg n=245 participants at risk 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.
Ear and labyrinth disorders Sudden hearing loss	0.40% 1/248 • Up to Week 14 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.	0.00% 0/245 • Up to Week 14 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.
Investigations ALT increased	0.00% 0/248 • Up to Week 14 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.	0.41% 1/245 • Up to Week 14 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.
Investigations Abnormal liver function test	0.40% 1/248 • Up to Week 14 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.	0.00% 0/245 • Up to Week 14 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.
Nervous system disorders Cerebral ischemia	0.40% 1/248 • Up to Week 14 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.	0.00% 0/245 • Up to Week 14 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cerebral hemangioma	0.00% 0/248 • Up to Week 14 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.	0.41% 1/245 • Up to Week 14 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic tumor	0.00% 0/248 • Up to Week 14 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.	0.41% 1/245 • Up to Week 14 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.
General disorders Local swelling	0.00% 0/248 • Up to Week 14 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.	0.41% 1/245 • Up to Week 14 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.
Cardiac disorders Acute coronary syndrome	0.00% 0/248 • Up to Week 14 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.	0.41% 1/245 • Up to Week 14 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.

Other adverse events

Measure	Metformin + Voglibose 0.2 mg n=248 participants at risk 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 + Acarbose 50 mg n=245 participants at risk 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.
Infections and infestations Urinary tract infection	6.0% 15/248 • Up to Week 14 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.	3.7% 9/245 • Up to Week 14 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.
Gastrointestinal disorders Flatulence	9.3% 23/248 • Up to Week 14 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.	16.7% 41/245 • Up to Week 14 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.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: trialdisclosures@takeda.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER