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

Institute for Clinical Effectiveness, Japan

Status and phase: Completed; Phase 4

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

Treatments: Drug: Sitagliptin; Drug: Anagliptin

Study type: Interventional

Funder types: Other

Identifiers

NCT02330406

ICE_2014_01R

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 353 patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

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

1. Presence of stenosis (>=25%) or plaque on the previous coronary angiography or coronary CT
2. Presence of coronary calcification on the previous coronary CT
3. History of acute coronary syndrome
4. History of percutaneous coronary intervention or coronary artery bypass graft
5. History of stroke (ischemic stroke or hemorrhagic stroke)
6. History of transient ischemic attack
7. History of peripheral artery diseases or aortic disorders
8. Ankle-Brachial Index (AMI) equal to or less than 0.9 in the past measurement
9. 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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353 participants in 2 patient groups

Anagliptin

Active Comparator group

Description:

Anagliptin 100 mg bid for 52 weeks. Can increase to 200 mg bid if needed.

Treatment:

Drug: Anagliptin

Sitagliptin

Active Comparator group

Description:

Sitagliptin 50 mg qd for 52 weeks. Can increase to 100 mg qd if needed

Treatment:

Drug: Sitagliptin