Study to Evaluate the Efficacy of Acarbose,Metformin,Sitagliptin Combination Treatment in DM Patients

• Sponsor: The Catholic University of Korea (Other)
• Overall Status: Completed
• CT.gov ID: NCT01490918
• Collaborator: Bayer (Industry)
• Enrollment: 165
• Location: 1
• Arms: 3
• Duration (Months): 29
• Patients Per Site Per Month: 5.7

Study Details

Study Description

Brief Summary

Primary objective To evaluate the efficacy of Acarbose add-on therapy on glucose control in subjects with type 2 diabetes inadequately controlled with Metformin and Sitagliptin combination therapy.

The effect of acarbose, an alpha glucosidase inhibitor as a third-line therapeutic medication in subject who are inadequately controlled with metformin and DPP4 inhibitor will be evaluated with multicenter, randomized, 24-week, double blinded, placebo-controlled study in Korea.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: Acarbose; Drug: Placebo acarbose; Drug: placebo metformin	Phase 4

Detailed Description

Eligible subjects will be assigned among 3 groups randomly at a ration of 2:2:1 to the following groups and primary efficacy variable analyzed at week 16.

group 1 : acarbose placebo + metformin + sitagliptin (with switching placebo to acarbose qt week 16) group 2 : acarbose + metformin + sitagliptin group 3 : acarbose + metformin placebo

• sitagliptin (with switching placebo to metformin at week 16)

After 16 week of treatment, all subjects in 3 groups will be treated as triple combination of acarbose + metformin + sitagliptin, and diabetes related variables be collected and analyzed.

1. Primary Endpoint Changes in HbA1c (hemoglobin A1c) at 16 week from baseline between group1 vs grou2

2. Secondary Endpoints (1) Changes of HbA1c at 24 week between 3 groups (2) Changed of post-prandial blood glucose at 2 hour (ppg2h) at 16, 24 week

for exploratory purpose, following data will be collected and analyzed

1. continuous glucose monitoring system (CGMS) data among selected subjects in 3 groups

2. mixed meal tolerance test in only available institution. (glucose, insulin, GLP-1, GIP, glucagon ) among selected subjects in group 1 and group 2

3. oxidative stress markers (8-OHdG, nitrotyrosin, CML)

4. self monitoring of blood glucose

Study Design

• Study Type: Interventional
• Actual Enrollment: 165 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: placebo medication
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double Blind, Placebo-controlled Study to Evaluate the Efficacy of Acarbose Added on Top of Metformin and Sitagliptin Combination Treatment in Type 2 Diabetes Mellitus Patients
• Study Start Date: Apr 1, 2012
• Actual Primary Completion Date: Sep 1, 2014
• Actual Study Completion Date: Sep 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Acarbose placebo, Metformin, Sitagliptin The Acarbose placebo should be changed into real Acarbose from the 16th week.	Drug: Placebo acarbose; acarbose placebo; Other Names: dual combination (metformin+sitagliptin)
Experimental: Sitagliptin, Metformin, Acarbose Metformin, Sitagliptin, Acarbose group	Drug: Acarbose; Acarbose 50mg b.i.d at first, at the 2nd week 50mg t.i.d and the 4th week, 100mg tid.; Other Names: triple combination
Other: Metformin placebo, Sitagliptin, Acarbose The Metformin placebo should be changed into real Metformin from the 16th week.	Drug: placebo metformin; metformin placebo; Other Names: dual combination (acarbose + sitagliptin)

Outcome Measures

Primary Outcome Measures

1. The Change of Glycated Hemoglogin(HbA1c) From Baseline to 16 Weeks of Treatment [baseline, 16 weeks]

   The change of glycated hemoglogin(HbA1c) from baseline to 16 weeks of treatment between Placebo + Metformin+Sitagliptin and Metformin + Sitagliptin + Acarbose group

Secondary Outcome Measures

1. The Change of HbA1c From Baseline to 24 Weeks of Treatment [baseline, 24 weeks]

   The change of glycated hemoglogin(HbA1c) from baseline to 24 weeks of treatment between 3 groups

2. The Change of PPG2hr From Baseline to 24 Weeks of Treatment [baseline, 24 weeks]

   The change of PPG2hr (post prandia blood glucose 2hr from baseline to 24 weeks of treatment between 3 groups

3. Changes in Glucose During Meal Tolerance Test Between 2 Group(Group 1 vs Group 2), [Visit 2(baseline) and Visit 5(16W)]

   Change of AUC(area under the curve) of glucose at 16 week from baseline between 2 groups (placebo+metformin + sitagliptin vs acarbose + metformin + sitagliptin)

4. Changes in Insulin During Mixed Meal Tolerance Test Between 2 Group(Group 1 vs Group 2), [Visit 2(baseline) and Visit 5(16W)]

   Change of AUC(area under the curve) of insulin at 16 week from baseline between 2 groups (placebo+metformin + sitagliptin vs acarbose + metformin + sitagliptin)

5. Change in Active GLP-1 at 0 Minute During Mixed Meal Test Between 2 Groups (Group 1, group2) [baseline, 16 week]

   Change of active GLP-1 at 0 minute during mixed meal test at 16 week from baseline between 2 groups(group1, group2)

6. Change in Active GLP-1 at 120 Minute During Mixed Meal Test Between 2 Groups (Group 1, group2) [baseline, 16 week]

   Change of active GLP-1 at 120 minute during mixed meal test at 16 week from baseline between 2 groups(group1, group2)

7. Changes in Glucagon During Meal Tolerance Test Between 2 Group(Group 1 vs Group 2), [Visit 2(baseline) and Visit 5(16W)]

   Change of AUC(area under the curve) of glucagon at 16 week from baseline between 2 groups (placebo+metformin + sitagliptin vs acarbose + metformin + sitagliptin)

Other Outcome Measures

1. Changes in Mean Glucose During CGMS Between 3 Group [Visit 2(baseline) and Visit 5(16W)]

   Change of mean glucose of CGMS(continuous glucose monitoring system) data at 16 week from baseline between 3 groups

2. Changes in Variation of Glucose During CGMS Between 3 Group [Visit 2(baseline) and Visit 5(16W)]

   Change of standard deviation of CGMS(continuous glucose monitoring system) data at 16 week from baseline between 3 groups (placebo+metformin + sitagliptin vs acarbose + metformin + sitagliptin vs placebo + acarbose + sitagliptin)

3. Changes in MAGE of Glucose During CGMS Between 2 Group(Group 1 vs Group 2), [Visit 2(baseline) and Visit 5(16W)]

   Change of mean amplitude of glycemic excursion of CGMS(continuous glucose monitoring system) data at 16 week from baseline between 2 groups (placebo+metformin + sitagliptin vs acarbose + metformin + sitagliptin)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Subjects with type-II diabetes mellitus;

2. Subjects aged between 20 and 80;

3. Subjects whose HbA1c ratio is between 7.0% and 10.0%;

4. Subjects who took Metformin and Sitagliptin for at least 12 weeks;

5. Subjects who were given the explanation about this clinical study and signed the consent form.

Exclusion Criteria:

1. Subjects who have taken drugs that are likely to affect blood glucose or who need to take such drugs, e.g., glucocorticoid;

2. Subjects with severe renal diseases (men: Scr>1.5 / women: Scr>1.4);

3. Subjects with severe liver diseases or whose AST and ALT are at least 2.5 times higher than the upper limits of normal (ULN);

4. Subjects having the case history of lactic acidosis;

5. Subjects who have the case history of myocardial infarction or unstable angina or who underwent the coronary artery bypass graft 6 months before the screening test or who have arrhythmia to be treated;

6. Subjects with congestive heart failures to be treated;

7. Subjects who fall into New York Heart Association (NYHA) class III or IV;

8. Subjects having the case history of acute or chronic metabolic acidosis including ketoacidosis;

9. Subjects who have been pregnant or who are in the period of lactation;

10. Subjects diagnosed with malignant tumors within 5 years;

11. Subjects who are hypersensitive to Metformin, Sitagliptin and Acarbose or their ingredients;

12. Subjects with inflammatory bowel diseases or intestinal ulcers or enterostenosis (includes Subjects who are vulnerable to enterostenosis) or chronic enteric diseases related to digestion and absorption or whose symptoms are likely to worsen due to intestinal gas;

13. Subjects who participated in other clinical studies as Subjects within 60 days before this study (or before taking the investigational drugs);

14. Subjects judged unfit for this study by investigators.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	MedicalExcellence	Seoul		Korea, Republic of	137-701

Sponsors and Collaborators

• The Catholic University of Korea
• Bayer

Investigators

• Principal Investigator: Kun-HO Yoon, professor, Seoul St. Mary's Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Kun-Ho Yoon, Professor, Medical doctor, The Catholic University of Korea
• ClinicalTrials.gov Identifier: NCT01490918
• Other Study ID Numbers: ACADEMIC
• First Posted: Dec 13, 2011
• Last Update Posted: Aug 17, 2020
• Last Verified: Jul 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Kun-Ho Yoon, Professor, Medical doctor, The Catholic University of Korea: Acarbose; ACADEMIC
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Metformin; Sitagliptin Phosphate; Acarbose

Study Results

Participant Flow

Arm/Group Title	Acarbose Placebo, Metformin, Sitagliptin	Sitagliptin, Metformin, Acarbose	Metformin Placebo, Sitagliptin, Acarbose
Arm/Group Description	Metformin and sitagliptin and placebo treatment for 16 weeks. Placebo was changed to acarbose at 16 week and maintained for another 8 weeks.	Metformin and sitagliptin and acarbose treatment for 24 weeks.	Placebo and sitagliptin and acarbose treatment for 16 weeks. Placebo was changed to acarbose at 16 week and maintained for another 8 weeks. The Metformin placebo should be changed into real Metformin from the 16th week.
Period Title: Overall Study
STARTED	65	66	34
COMPLETED	52	52	22
NOT COMPLETED	13	14	12

Baseline Characteristics

Arm/Group Title	Acarbose Placebo, Metformin, Sitagliptin	Sitagliptin, Metformin, Acarbose	Metformin Placebo, Sitagliptin, Acarbose	Total
Arm/Group Description	The dose of Acarbose should be 50mg b.i.d, 50mg t.i.d and 100mg t.i.d at the 18th week, the 20th week and the 24th week respectively. The Acarbose placebo should be changed into real Acarbose from the 16th week. Acarbose: The dose of Acarbose or its placebo should be 50mg b.i.d at first. At the 2nd week and the 4th week, it should be 50mg t.i.d and 100mg t.i.d respectively	The group's drugs not include placebo. (Metformin, Sitagliptin, Acarbose) Acarbose: The dose of Acarbose or its placebo should be 50mg b.i.d at first. At the 2nd week and the 4th week, it should be 50mg t.i.d and 100mg t.i.d respectively	The Metformin placebo should be changed into real Metformin from the 16th week. Acarbose: The dose of Acarbose or its placebo should be 50mg b.i.d at first. At the 2nd week and the 4th week, it should be 50mg t.i.d and 100mg t.i.d respectively	Total of all reporting groups
Overall Participants	65	66	34	165
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.55 (10.51)	60.89 (8.8)	60.15 (9.92)	59.03 (9.88)
Sex: Female, Male (Count of Participants)
Female	30 46.2%	43 65.2%	14 41.2%	87 52.7%
Male	35 53.8%	23 34.8%	20 58.8%	78 47.3%
Region of Enrollment (participants) [Number]
South Korea	65 100%	66 100%	34 100%	165 100%

Outcome Measures

1. Primary Outcome

Title	The Change of Glycated Hemoglogin(HbA1c) From Baseline to 16 Weeks of Treatment
Description	The change of glycated hemoglogin(HbA1c) from baseline to 16 weeks of treatment between Placebo + Metformin+Sitagliptin and Metformin + Sitagliptin + Acarbose group
Time Frame	baseline, 16 weeks

Outcome Measure Data

Analysis Population Description

ITT: intention to treatment, All subject randomized to each treatment group

Arm/Group Title	Placebo+Metformin+Sitagliptin	Sitagliptin+Metformin+Acarbose	Placebo+Sitagliptin+Acarbose
Arm/Group Description	Metformin and sitagliptin and placebo treatment for 16 weeks. Placebo was changed to acarbose at 16 week and maintained for another 8 weeks as triple combination of acarbose + metformin + sitagliptin	Metformin and sitagliptin and acarbose treatment for 24 weeks.	Placebo and sitagliptin and acarbose treatment for 16 weeks. The placebo will be changed to Metformin from the 16th week and maintained another 8 week for triple combination of metformin + sitagliptin + acarbose.
Measure Participants	65	66	34
Mean (Standard Error) [% of HbA1c]	-0.09 (0.1)	-0.44 (0.08)	0.84 (0.21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo+Metformin+Sitagliptin, Sitagliptin+Metformin+Acarbose
	Comments	primary outcome efficacy will be evaluated between group 1(placebo + metfromin + sitagliptin) and 2 (sitagliptine + metformin + acarbose)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0036
	Comments	The threshold for statistical significance was p=0.05
	Method	ANCOVA
	Comments	Baselin HbA1c as covariate

2. Secondary Outcome

Title	The Change of HbA1c From Baseline to 24 Weeks of Treatment
Description	The change of glycated hemoglogin(HbA1c) from baseline to 24 weeks of treatment between 3 groups
Time Frame	baseline, 24 weeks

Outcome Measure Data

Analysis Population Description

ITT: intention to treatment, All subject randomized to each treatment group

Arm/Group Title	Placebo+Metformin+Sitagliptin	Sitagliptin+Metformin+Acarbose	Placebo+Sitagliptin+Acarbose
Arm/Group Description	Metformin and sitagliptin and placebo treatment for 16 weeks. Placebo was changed to acarbose at 16 week and maintained for another 8 weeks as triple combination of acarbose + metformin + sitagliptin	Metformin and sitagliptin and acarbose treatment for 24 weeks.	Placebo and sitagliptin and acarbose treatment for 16 weeks. The placebo will be changed to Metformin from the 16th week and maintained another 8 week for triple combination of metformin + sitagliptin + acarbose.
Measure Participants	65	66	34
Mean (Standard Deviation) [% of HbA1c]	-0.34 (0.82)	-0.47 (0.78)	0.23 (1.32)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo+Metformin+Sitagliptin, Sitagliptin+Metformin+Acarbose, Placebo+Sitagliptin+Acarbose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The threshold for statistical significance was p=0.05
	Method	ANCOVA
	Comments	Baseline HbA1c as covariate

3. Secondary Outcome

Title	The Change of PPG2hr From Baseline to 24 Weeks of Treatment
Description	The change of PPG2hr (post prandia blood glucose 2hr from baseline to 24 weeks of treatment between 3 groups
Time Frame	baseline, 24 weeks

Outcome Measure Data

Analysis Population Description

ITT: intention to treatment, All subject randomized to each treatment group

Arm/Group Title	Placebo+Metformin+Sitagliptin	Sitagliptin+Metformin+Acarbose	Placebo+Sitagliptin+Acarbose
Arm/Group Description	Metformin and sitagliptin and placebo treatment for 16 weeks. Placebo was changed to acarbose at 16 week and maintained for another 8 weeks.	Metformin and sitagliptin and acarbose treatment for 24 weeks.	Placebo and sitagliptin and acarbose treatment for 16 weeks. Placebo was changed to acarbose at 16 week and maintained for another 8 weeks. The Metformin placebo should be changed into real Metformin from the 16th week.
Measure Participants	63	66	34
Mean (Standard Deviation) [mmol/L]	-1.73 (3.38)	-1.76 (3.53)	0.06 (4.53)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo+Metformin+Sitagliptin, Sitagliptin+Metformin+Acarbose, Placebo+Sitagliptin+Acarbose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0185
	Comments	The threshold for statistical significance was p=0.05
	Method	ANCOVA
	Comments	baseline PPG2hr as covariate

4. Secondary Outcome

Title	Changes in Glucose During Meal Tolerance Test Between 2 Group(Group 1 vs Group 2),
Description	Change of AUC(area under the curve) of glucose at 16 week from baseline between 2 groups (placebo+metformin + sitagliptin vs acarbose + metformin + sitagliptin)
Time Frame	Visit 2(baseline) and Visit 5(16W)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo+Metformin+Sitagliptin	Sitagliptin+Metformin+Acarbose
Arm/Group Description	Metformin and sitagliptin and placebo treatment for 16 weeks. Placebo was changed to acarbose at 16 week and maintained for another 8 weeks.	Metformin and sitagliptin and acarbose treatment for 24 weeks.
Measure Participants	12	13
Mean (Standard Deviation) [mg min/dL]	28.85 (2168.64)	-743.08 (1278.28)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo+Metformin+Sitagliptin, Sitagliptin+Metformin+Acarbose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0356
	Comments	The threshold for statistical significance was p=0.05
	Method	ANCOVA
	Comments	baseline data as covariate

5. Secondary Outcome

Title	Changes in Insulin During Mixed Meal Tolerance Test Between 2 Group(Group 1 vs Group 2),
Description	Change of AUC(area under the curve) of insulin at 16 week from baseline between 2 groups (placebo+metformin + sitagliptin vs acarbose + metformin + sitagliptin)
Time Frame	Visit 2(baseline) and Visit 5(16W)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo+Metformin+Sitagliptin	Sitagliptin+Metformin+Acarbose
Arm/Group Description	Metformin and sitagliptin and placebo treatment for 16 weeks. Placebo was changed to acarbose at 16 week and maintained for another 8 weeks.	Metformin and sitagliptin and acarbose treatment for 24 weeks.
Measure Participants	13	12
Mean (Standard Deviation) [pg min/mL]	647.65 (3854.75)	221.42 (8339.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo+Metformin+Sitagliptin, Sitagliptin+Metformin+Acarbose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8258
	Comments	The threshold for statistical significance was p=0.05
	Method	ANCOVA
	Comments	baseline data as covariate

6. Secondary Outcome

Title	Change in Active GLP-1 at 0 Minute During Mixed Meal Test Between 2 Groups (Group 1, group2)
Description	Change of active GLP-1 at 0 minute during mixed meal test at 16 week from baseline between 2 groups(group1, group2)
Time Frame	baseline, 16 week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo+Metformin+Sitagliptin	Sitagliptin+Metformin+Acarbose
Arm/Group Description	Metformin and sitagliptin and placebo treatment for 16 weeks. Placebo was changed to acarbose at 16 week and maintained for another 8 weeks.	Metformin and sitagliptin and acarbose treatment for 24 weeks.
Measure Participants	12	13
Mean (Standard Deviation) [pg/ml]	-8.55 (19.01)	-9.33 (31.12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo+Metformin+Sitagliptin, Sitagliptin+Metformin+Acarbose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9217
	Comments	The threshold for statistical significance was p=0.05
	Method	ANCOVA
	Comments	baseline data as covariate

7. Secondary Outcome

Title	Change in Active GLP-1 at 120 Minute During Mixed Meal Test Between 2 Groups (Group 1, group2)
Description	Change of active GLP-1 at 120 minute during mixed meal test at 16 week from baseline between 2 groups(group1, group2)
Time Frame	baseline, 16 week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo+Metformin+Sitagliptin	Sitagliptin+Metformin+Acarbose
Arm/Group Description	Metformin and sitagliptin and placebo treatment for 16 weeks. Placebo was changed to acarbose at 16 week and maintained for another 8 weeks.	Metformin and sitagliptin and acarbose treatment for 24 weeks.
Measure Participants	12	13
Mean (Standard Deviation) [pg/ml]	-32.92 (21.78)	-23.36 (33.43)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo+Metformin+Sitagliptin, Sitagliptin+Metformin+Acarbose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.16
	Comments	The threshold for statistical significance was p=0.05
	Method	ANCOVA
	Comments	baseline data as covariate

8. Secondary Outcome

Title	Changes in Glucagon During Meal Tolerance Test Between 2 Group(Group 1 vs Group 2),
Description	Change of AUC(area under the curve) of glucagon at 16 week from baseline between 2 groups (placebo+metformin + sitagliptin vs acarbose + metformin + sitagliptin)
Time Frame	Visit 2(baseline) and Visit 5(16W)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo+Metformin+Sitagliptin	Sitagliptin+Metformin+Acarbose
Arm/Group Description	Metformin and sitagliptin and placebo treatment for 16 weeks. Placebo was changed to acarbose at 16 week and maintained for another 8 weeks.	Metformin and sitagliptin and acarbose treatment for 24 weeks.
Measure Participants	9	9
Mean (Standard Deviation) [min pg/mL]	-79.22 (833.59)	-1411.79 (1049.41)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo+Metformin+Sitagliptin, Sitagliptin+Metformin+Acarbose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments	The threshold for statistical significance was p=0.05
	Method	ANCOVA
	Comments	baseline data as covariate

9. Other Pre-specified Outcome

Title	Changes in Mean Glucose During CGMS Between 3 Group
Description	Change of mean glucose of CGMS(continuous glucose monitoring system) data at 16 week from baseline between 3 groups
Time Frame	Visit 2(baseline) and Visit 5(16W)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo+Metformin+Sitagliptin	Sitagliptin+Metformin+Acarbose	Placebo + Sitagliptin + Acarbose
Arm/Group Description	Metformin and sitagliptin and placebo treatment for 16 weeks. Placebo was changed to acarbose at 16 week and maintained for another 8 weeks as triple combination of acarbose + metformin + sitagliptin	Metformin and sitagliptin and acarbose treatment for 24 weeks.	Placebo and sitagliptin and acarbose treatment for 16 weeks. The placebo will be changed to Metformin from the 16th week and maintained another 8 week for triple combination of metformin + sitagliptin + acarbose.
Measure Participants	11	13	6
Mean (Standard Deviation) [mmol/L]	-0.91 (0.81)	-1.16 (0.49)	3.22 (1.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo+Metformin+Sitagliptin, Sitagliptin+Metformin+Acarbose, Placebo+Sitagliptin+Acarbose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.292
	Comments	The threshold for statistical significance was p=0.05
	Method	ANCOVA
	Comments	baseline data as covariate

10. Other Pre-specified Outcome

Title	Changes in Variation of Glucose During CGMS Between 3 Group
Description	Change of standard deviation of CGMS(continuous glucose monitoring system) data at 16 week from baseline between 3 groups (placebo+metformin + sitagliptin vs acarbose + metformin + sitagliptin vs placebo + acarbose + sitagliptin)
Time Frame	Visit 2(baseline) and Visit 5(16W)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo+Metformin+Sitagliptin	Sitagliptin+Metformin+Acarbose	Placebo + Acarbose + Sitagliptin
Arm/Group Description	Metformin and sitagliptin and placebo treatment for 16 weeks. Placebo was changed to acarbose at 16 week and maintained for another 8 weeks as triple combination of acarbose + metformin + sitagliptin	Metformin and sitagliptin and acarbose treatment for 24 weeks.	Placebo and sitagliptin and acarbose treatment for 16 weeks. The placebo will be changed to Metformin from the 16th week and maintained another 8 week for triple combination of metformin + sitagliptin + acarbose.
Measure Participants	11	13	6
Mean (Standard Deviation) [mmol/L]	-0.33 (1.0)	-0.65 (0.8)	0.03 (0.29)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo+Metformin+Sitagliptin, Sitagliptin+Metformin+Acarbose, Placebo+Sitagliptin+Acarbose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.314
	Comments	The threshold for statistical significance was p=0.05
	Method	ANCOVA
	Comments	baseline data as covariate

11. Other Pre-specified Outcome

Title	Changes in MAGE of Glucose During CGMS Between 2 Group(Group 1 vs Group 2),
Description	Change of mean amplitude of glycemic excursion of CGMS(continuous glucose monitoring system) data at 16 week from baseline between 2 groups (placebo+metformin + sitagliptin vs acarbose + metformin + sitagliptin)
Time Frame	Visit 2(baseline) and Visit 5(16W)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo+Metformin+Sitagliptin	Sitagliptin+Metformin+Acarbose	Placebo + Acarbose + Sitagliptin
Arm/Group Description	Metformin and sitagliptin and placebo treatment for 16 weeks. Placebo was changed to acarbose at 16 week and maintained for another 8 weeks as triple combination of acarbose + metformin + sitagliptin	Metformin and sitagliptin and acarbose treatment for 24 weeks.	Placebo and sitagliptin and acarbose treatment for 16 weeks. The placebo will be changed to Metformin from the 16th week and maintained another 8 week for triple combination of metformin + sitagliptin + acarbose.
Measure Participants	11	13	6
Mean (Standard Deviation) [mg/dL]	-8.79 (15.01)	-18.5 (13.23)	2.72 (2.72)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo+Metformin+Sitagliptin, Sitagliptin+Metformin+Acarbose, Placebo+Sitagliptin+Acarbose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7563
	Comments	The threshold for statistical significance was p=0.05
	Method	ANCOVA
	Comments	baseline data as covariate

Adverse Events

Time Frame	24 weeks
Adverse Event Reporting Description	total number afffected by any other adverse event : included SAEs
Arm/Group Title	Acarbose Placebo, Metformin, Sitagliptin		Sitagliptin, Metformin, Acarbose		Metformin Placebo, Sitagliptin, Acarbose
Arm/Group Description	The dose of Acarbose should be 50mg b.i.d, 50mg t.i.d and 100mg t.i.d at the 18th week, the 20th week and the 24th week respectively. The Acarbose placebo should be changed into real Acarbose from the 16th week. Acarbose: The dose of Acarbose or its placebo should be 50mg b.i.d at first. At the 2nd week and the 4th week, it should be 50mg t.i.d and 100mg t.i.d respectively		The group's drugs not include placebo. (Metformin, Sitagliptin, Acarbose) Acarbose: The dose of Acarbose or its placebo should be 50mg b.i.d at first. At the 2nd week and the 4th week, it should be 50mg t.i.d and 100mg t.i.d respectively		The Metformin placebo should be changed into real Metformin from the 16th week. Acarbose: The dose of Acarbose or its placebo should be 50mg b.i.d at first. At the 2nd week and the 4th week, it should be 50mg t.i.d and 100mg t.i.d respectively
All Cause Mortality
	Acarbose Placebo, Metformin, Sitagliptin		Sitagliptin, Metformin, Acarbose		Metformin Placebo, Sitagliptin, Acarbose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/65 (0%)		0/66 (0%)		0/34 (0%)
Serious Adverse Events
	Acarbose Placebo, Metformin, Sitagliptin		Sitagliptin, Metformin, Acarbose		Metformin Placebo, Sitagliptin, Acarbose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/65 (3.1%)		1/66 (1.5%)		0/34 (0%)
General disorders
chest pain	1/65 (1.5%)	1	0/66 (0%)	0	0/34 (0%)	0
Musculoskeletal and connective tissue disorders
lumbar spinal stenosis	1/65 (1.5%)	1	0/66 (0%)	0	0/34 (0%)	0
Spinal osteoarthritis	0/65 (0%)	0	1/66 (1.5%)	1	0/34 (0%)	0
Other (Not Including Serious) Adverse Events
	Acarbose Placebo, Metformin, Sitagliptin		Sitagliptin, Metformin, Acarbose		Metformin Placebo, Sitagliptin, Acarbose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/65 (21.5%)		19/66 (28.8%)		11/34 (32.4%)
Eye disorders
cataract	1/65 (1.5%)	1	0/66 (0%)	0	0/34 (0%)	0
visual acuity reduced	0/65 (0%)	0	0/66 (0%)	0	1/34 (2.9%)	1
Gastrointestinal disorders
abdominal discomfort	2/65 (3.1%)	2	2/66 (3%)	2	0/34 (0%)	0
abdominal distension	0/65 (0%)	0	1/66 (1.5%)	1	1/34 (2.9%)	1
abdominal pain	0/65 (0%)	0	1/66 (1.5%)	1	0/34 (0%)	0
chronic gastritis	0/65 (0%)	0	0/66 (0%)	0	1/34 (2.9%)	1
constipation	1/65 (1.5%)	1	1/66 (1.5%)	1	0/34 (0%)	0
dental caries	0/65 (0%)	0	1/66 (1.5%)	1	0/34 (0%)	0
diarrhea	1/65 (1.5%)	1	1/66 (1.5%)	1	0/34 (0%)	0
dyspepsia	2/65 (3.1%)	2	6/66 (9.1%)	6	0/34 (0%)	0
flatulence	1/65 (1.5%)	1	2/66 (3%)	2	0/34 (0%)	0
large intestinal polyp	0/65 (0%)	0	0/66 (0%)	0	1/34 (2.9%)	1
nausea	1/65 (1.5%)	1	1/66 (1.5%)	1	1/34 (2.9%)	1
toothcache	0/65 (0%)	0	1/66 (1.5%)	1	0/34 (0%)	0
vomiting	1/65 (1.5%)	1	1/66 (1.5%)	1	0/34 (0%)	0
General disorders
chest pain	1/65 (1.5%)	1	0/66 (0%)	0	0/34 (0%)	0
Infections and infestations
hordeolum	1/65 (1.5%)	1	0/66 (0%)	0	0/34 (0%)	0
nasopharyngitis	1/65 (1.5%)	1	2/66 (3%)	3	1/34 (2.9%)	1
urinary tract infection	0/65 (0%)	0	1/66 (1.5%)	1	0/34 (0%)	0
Injury, poisoning and procedural complications
laceration	0/65 (0%)	0	0/66 (0%)	0	1/34 (2.9%)	1
tooth fracture	1/65 (1.5%)	1	0/66 (0%)	0	0/34 (0%)	0
wrist fracture	1/65 (1.5%)	1	0/66 (0%)	0	0/34 (0%)	0
Investigations
ALT increased	1/65 (1.5%)	1	0/66 (0%)	0	0/34 (0%)	0
AST increased	1/65 (1.5%)	1	0/66 (0%)	0	0/34 (0%)	0
liver function test abnormal	1/65 (1.5%)	1	0/66 (0%)	0	0/34 (0%)	0
Metabolism and nutrition disorders
diabetes mellitus inadequate controll	1/65 (1.5%)	1	0/66 (0%)	0	0/34 (0%)	0
hyperglycemia	0/65 (0%)	0	0/66 (0%)	0	4/34 (11.8%)	4
hypoglycemia	0/65 (0%)	0	1/66 (1.5%)	1	1/34 (2.9%)	2
Musculoskeletal and connective tissue disorders
lumbar spinal stenosis	1/65 (1.5%)	1	0/66 (0%)	0	0/34 (0%)	0
musculoskeletal pain	0/65 (0%)	0	0/66 (0%)	0	1/34 (2.9%)	1
pain in extremity	0/65 (0%)	0	1/66 (1.5%)	1	0/34 (0%)	0
spinal osteoarthritis	0/65 (0%)	0	1/66 (1.5%)	1	0/34 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
uterine leimyoma	0/65 (0%)	0	1/66 (1.5%)	1	0/34 (0%)	0
Nervous system disorders
dizziness	0/65 (0%)	0	1/66 (1.5%)	1	1/34 (2.9%)	1
paresthesia	0/65 (0%)	0	0/66 (0%)	0	1/34 (2.9%)	1
tremor	0/65 (0%)	0	1/66 (1.5%)	1	0/34 (0%)	0
Renal and urinary disorders
prorteinuria	1/65 (1.5%)	1	0/66 (0%)	0	0/34 (0%)	0
Reproductive system and breast disorders
pelvic pain	0/65 (0%)	0	1/66 (1.5%)	1	0/34 (0%)	0
Skin and subcutaneous tissue disorders
pruritus	0/65 (0%)	0	2/66 (3%)	2	0/34 (0%)	0
skin exfoliation	0/65 (0%)	0	1/66 (1.5%)	1	0/34 (0%)	0
vitiligo	0/65 (0%)	0	1/66 (1.5%)	1	0/34 (0%)	0

Limitations/Caveats

Evaluation of GIP and oxidative stress markers (8-OHdG, Nitrotyrosin) were not analyzed due to limited number of sample and technical problems leading to uninterpretable data.

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.