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

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

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.

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

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.