Randomized Evaluation of Anagliptin Versus Sitagliptin On Low-density lipoproteiN Cholesterol in Diabetes Trial

Study Overview
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Brief Summary
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The purpose of this study is to determine whether Anagliptin or Sitagliptin are effective in reducing the low-density lipoprotein cholesterol in patients with type 2 diabetes and cardiovascular risk factors on statin.

Detailed Description
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Diabetes is a significant cause of cardiovascular and cerebrovascular events. Especially, diabetic patients with cardiovascular risk factors were significantly higher risk for cardiovascular and cerebrovasculara event. Therefore, several medical management strategies including anti-diabetic medications and statins were considered for those patients. However, in spite of such treatment, still many patients have cardiovascular and cerebrovascular events. One of the hypothesis is the residual risk such as elevated low-density lipoprotein cholesterol (LDLC) even with statin therapy. Anagliptin, one of the dipeptidyl peptidase-4 (DPP4) inhibiors, was reported to reduce LDLC and may have pontential to decrease the cardiovascular and cerebrovascular risk for such patients on statins. We, thus, conduct a randomized controlled trial to compare Anagliptin or Sitagliptin in terms of change of LDLC for 52 weeks as well as glycemic control.

Official Title
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Effect of Anagliptin and Sitagliptin on Low-density Lipoprotein Cholesterol in Patients With Type 2 Diabetes and Cardiovascular Risk Factors: Randomized Controlled Trial

Conditions
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Dipeptidyl-Peptidase 4 Inhibitors, LDL Cholesterol, Glycosylated Hemoglobin, Diabetes Mellitus, Coronary Disease

Intervention / Treatment
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* Drug: Anagliptin
* Drug: Sitagliptin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with type 2 diabetes with cardiovascular risk factors (*) who treated with diet, exercise or antidiabetic medications Patients who were treated with statins for 8 weeks or longer Patients with low-density lipoprotein cholesterol equal to or greater than 100 mg/dL in the at least one of three measurements after the administration of statins Patients with glycerated hemoglobin (HbA1c, NGSP) equal to or greater than 6.0 % (7.0 % if patients were not treated with dipeptidyl-peptidase 4 inhibitors) and lesser than 10.5 % (*) cardiovascular risk factors were any of following conditions Presence of stenosis (>=25%) or plaque on the previous coronary angiography or coronary CT Presence of coronary calcification on the previous coronary CT History of acute coronary syndrome History of percutaneous coronary intervention or coronary artery bypass graft History of stroke (ischemic stroke or hemorrhagic stroke) History of transient ischemic attack History of peripheral artery diseases or aortic disorders Ankle-Brachial Index (AMI) equal to or less than 0.9 in the past measurement Presence of carotid artery plaque (including Max IMT >=1.1mm) on carotid ultrasonography in the past Exclusion Criteria: Patients with type 1 diabetes Patients with triglyceride equal to or greater than 400 mg/dL in the previous fasting measurements Patients with pregnancy, possible pregnancy, or on breast-feeding Patients with severe infections, perioperative status, or severe trauma Patients with renal dysfunction (creatinine >= 2.4 mg/dl for men, >= 2.0 mg/dl for women) Patients who were received glucagon-like peptide-1receptor agonists Patients whom physician in charge considered inappropriate for the study

Ages Eligible for Study
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Minimum Age: 20 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Anagliptin<br>Anagliptin 100 mg bid for 52 weeks. Can increase to 200 mg bid if needed. | Drug: Anagliptin<br>* Suiny 100 mg<br>* Other names: Suiny;|
| Active Comparator: Sitagliptin<br>Sitagliptin 50 mg qd for 52 weeks. Can increase to 100 mg qd if needed | Drug: Sitagliptin<br>* Januvia 50 mg Glactiv 50 mg<br>* Other names: Glactiv;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in low-density lipoprotein cholesterol |  | 52-weeks | 
| Change in glycated hemoglobin |  | 52-weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in fasting glucose |  | 52-weeks | 
| Change in fasting insulin |  | 52-weeks | 
| Change in 1.5-Anhydro-D-glucitol |  | 52-weeks | 
| Change in C peptide |  | 52-weeks | 
| Change in total cholesterol, triglyceride, non high dencisty lipoprotein cholesterol |  | 52-weeks | 
| Change in Apolipoprotein A1, Apolipoprotein B, Apolipoprotein E |  | 52-weeks | 
| Change in Apolipoprotein B48 |  | 52-weeks | 
| Change in small dense low density lipoprotein |  | 52-weeks | 
| Change in high sensitivity C-reactive protein |  | 52-weeks | 
| Change in interleukin-6 |  | 52-weeks | 
| Change in cholesterol absorption marker (campesterol; sitosterol) |  | 52-weeks | 
| Change in cholesterol synthesis marker (lathosterol) |  | 52-weeks | 
| Change in high molecular weight adiponectin |  | 52-weeks | 
| Change in ratio of albumin and creatinine in urine |  | 52-weeks | 
| Progression, unchange, remission rate of microalbumin and macroalbumin in urine |  | 52-weeks | 
| Change in estimated glomerular filtration rate |  | 52-weeks | 
| Change in glycated hemoglobin stratified by body mass index and waist circumference |  | 52-weeks | 
| Correlation between glycated hemoglobin and body mass index or waist circumference |  | 52-weeks | 
| Change in intima-media thickness or flow mediated dilation |  | 52-weeks | 
| Change in postprandial glucose, insulin and activated glucagon-like peptide-1 |  | 52-weeks | 
| Change in lipid profile and molecular size measured |  | 52-weeks | 
| Change in fatty acid fraction |  | 52-weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dipeptidyl-Peptidase 4 Inhibitors, LDL Cholesterol, Glycosylated Hemoglobin, Diabetes Mellitus, Coronary Disease