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

Study Overview
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Brief Summary
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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.

Detailed Description
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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. Primary Endpoint Changes in HbA1c (hemoglobin A1c) at 16 week from baseline between group1 vs grou2 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 continuous glucose monitoring system (CGMS) data among selected subjects in 3 groups mixed meal tolerance test in only available institution. (glucose, insulin, GLP-1, GIP, glucagon ) among selected subjects in group 1 and group 2 oxidative stress markers (8-OHdG, nitrotyrosin, CML) self monitoring of blood glucose

Official Title
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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

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Acarbose
* Drug: Placebo acarbose
* Drug: placebo metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with type-II diabetes mellitus; Subjects aged between 20 and 80; Subjects whose HbA1c ratio is between 7.0% and 10.0%; Subjects who took Metformin and Sitagliptin for at least 12 weeks; Subjects who were given the explanation about this clinical study and signed the consent form. Exclusion Criteria: Subjects who have taken drugs that are likely to affect blood glucose or who need to take such drugs, e.g., glucocorticoid; Subjects with severe renal diseases (men: Scr>1.5 / women: Scr>1.4); Subjects with severe liver diseases or whose AST and ALT are at least 2.5 times higher than the upper limits of normal (ULN); Subjects having the case history of lactic acidosis; 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; Subjects with congestive heart failures to be treated; Subjects who fall into New York Heart Association (NYHA) class III or IV; Subjects having the case history of acute or chronic metabolic acidosis including ketoacidosis; Subjects who have been pregnant or who are in the period of lactation; Subjects diagnosed with malignant tumors within 5 years; Subjects who are hypersensitive to Metformin, Sitagliptin and Acarbose or their ingredients; 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; Subjects who participated in other clinical studies as Subjects within 60 days before this study (or before taking the investigational drugs); Subjects judged unfit for this study by investigators.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Change of HbA1c From Baseline to 24 Weeks of Treatment | The change of glycated hemoglogin(HbA1c) from baseline to 24 weeks of treatment between 3 groups | baseline, 24 weeks | 
| The Change of PPG2hr From Baseline to 24 Weeks of Treatment | The change of PPG2hr (post prandia blood glucose 2hr from baseline to 24 weeks of treatment between 3 groups | baseline, 24 weeks | 
| Changes in Glucose During Meal Tolerance Test Between 2 Group(Group 1 vs Group 2), | Change of AUC(area under the curve) of glucose at 16 week from baseline between 2 groups (placebo+metformin + sitagliptin vs acarbose + metformin + sitagliptin) | Visit 2(baseline) and Visit 5(16W) | 
| Changes in Insulin During Mixed Meal Tolerance Test Between 2 Group(Group 1 vs Group 2), | Change of AUC(area under the curve) of insulin at 16 week from baseline between 2 groups (placebo+metformin + sitagliptin vs acarbose + metformin + sitagliptin) | Visit 2(baseline) and Visit 5(16W) | 
| Change in Active GLP-1 at 0 Minute During Mixed Meal Test Between 2 Groups (Group 1, group2) | Change of active GLP-1 at 0 minute during mixed meal test at 16 week from baseline between 2 groups(group1, group2) | baseline, 16 week | 
| Change in Active GLP-1 at 120 Minute During Mixed Meal Test Between 2 Groups (Group 1, group2) | Change of active GLP-1 at 120 minute during mixed meal test at 16 week from baseline between 2 groups(group1, group2) | baseline, 16 week | 
| Changes in Glucagon During Meal Tolerance Test Between 2 Group(Group 1 vs Group 2), | Change of AUC(area under the curve) of glucagon at 16 week from baseline between 2 groups (placebo+metformin + sitagliptin vs acarbose + metformin + sitagliptin) | Visit 2(baseline) and Visit 5(16W) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acarbose, ACADEMIC