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

NCT ID: NCT02330406

Last Updated: 2019-08-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 353 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-30
• Study Completion Date: 2019-03-31

Brief Summary

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

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Anagliptin

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

Group Type: ACTIVE_COMPARATOR

Anagliptin

Intervention Type: DRUG

Suiny 100 mg

Sitagliptin

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

Group Type: ACTIVE_COMPARATOR

Sitagliptin

Intervention Type: DRUG

Januvia 50 mg Glactiv 50 mg

Interventions

Anagliptin

Suiny 100 mg

Intervention Type: DRUG

Sitagliptin

Januvia 50 mg Glactiv 50 mg

Intervention Type: DRUG

Other Intervention Names

Suiny; Januvia; Glactiv

Eligibility Criteria

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

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institute for Clinical Effectiveness, Japan

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shinichiro Ueda, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Professor of Medicine, Department of Clinical Pharmacology & Therapeutics, University of the Ryukyus

Locations

Department of Cardiovascular Medicine, Tomishiro Central Hospital

Tomishiro, Okinawa, Japan

Countries

Japan

References

Furuhashi M, Sakuma I, Morimoto T, Higashiura Y, Sakai A, Matsumoto M, Sakuma M, Shimabukuro M, Nomiyama T, Arasaki O, Node K, Ueda S. Treatment with anagliptin, a DPP-4 inhibitor, decreases FABP4 concentration in patients with type 2 diabetes mellitus at a high risk for cardiovascular disease who are receiving statin therapy. Cardiovasc Diabetol. 2020 Jun 15;19(1):89. doi: 10.1186/s12933-020-01061-0.

Reference Type: DERIVED

PMID: 32539832 (View on PubMed)

Chihara A, Tanaka A, Morimoto T, Sakuma M, Shimabukuro M, Nomiyama T, Arasaki O, Ueda S, Node K. Differences in lipid metabolism between anagliptin and sitagliptin in patients with type 2 diabetes on statin therapy: a secondary analysis of the REASON trial. Cardiovasc Diabetol. 2019 Nov 16;18(1):158. doi: 10.1186/s12933-019-0965-3.

Reference Type: DERIVED

PMID: 31733647 (View on PubMed)

Morimoto T, Sakuma I, Sakuma M, Tokushige A, Natsuaki M, Asahi T, Shimabukuro M, Nomiyama T, Arasaki O, Node K, Ueda S. Randomized Evaluation of Anagliptin vs Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) Trial: A 52-week, open-label, randomized clinical trial. Sci Rep. 2019 Jun 12;9(1):8537. doi: 10.1038/s41598-019-44885-x.

Reference Type: DERIVED

PMID: 31189978 (View on PubMed)

Ueda S, Shimabukuro M, Arasaki O, Node K, Nomiyama T, Morimoto T. Effect of Anagliptin and Sitagliptin on Low-Density Lipoprotein Cholesterol in Type 2 Diabetic Patients with Dyslipidemia and Cardiovascular Risk: Rationale and Study Design of the REASON Trial. Cardiovasc Drugs Ther. 2018 Feb;32(1):73-80. doi: 10.1007/s10557-018-6776-z.

Reference Type: DERIVED

PMID: 29435776 (View on PubMed)

Other Identifiers

ICE_2014_01R

Identifier Type: -

Identifier Source: org_study_id