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
Overview
- Phase
- Phase 4
- Intervention
- Placebo acarbose
- Conditions
- Type 2 Diabetes Mellitus
- Sponsor
- The Catholic University of Korea
- Enrollment
- 165
- Locations
- 1
- Primary Endpoint
- The Change of Glycated Hemoglogin(HbA1c) From Baseline to 16 Weeks of Treatment
- Status
- Completed
- Last Updated
- 5 years ago
Overview
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.
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
Investigators
Kun-Ho Yoon
Professor, Medical doctor
The Catholic University of Korea
Eligibility Criteria
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;
Arms & Interventions
Acarbose placebo, Metformin, Sitagliptin
The Acarbose placebo should be changed into real Acarbose from the 16th week.
Intervention: Placebo acarbose
Sitagliptin, Metformin, Acarbose
Metformin, Sitagliptin, Acarbose group
Intervention: Acarbose
Metformin placebo, Sitagliptin, Acarbose
The Metformin placebo should be changed into real Metformin from the 16th week.
Intervention: placebo metformin
Outcomes
Primary Outcomes
The Change of Glycated Hemoglogin(HbA1c) From Baseline to 16 Weeks of Treatment
Time Frame: 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 Outcomes
- The Change of HbA1c From Baseline to 24 Weeks of Treatment(baseline, 24 weeks)
- The Change of PPG2hr From Baseline to 24 Weeks of Treatment(baseline, 24 weeks)
- Changes in Glucose During Meal Tolerance Test Between 2 Group(Group 1 vs Group 2),(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)(baseline, 16 week)
- Change in Active GLP-1 at 120 Minute During Mixed Meal Test Between 2 Groups (Group 1, group2)(baseline, 16 week)
- Changes in Insulin During Mixed Meal Tolerance Test Between 2 Group(Group 1 vs Group 2),(Visit 2(baseline) and Visit 5(16W))
- Changes in Glucagon During Meal Tolerance Test Between 2 Group(Group 1 vs Group 2),(Visit 2(baseline) and Visit 5(16W))