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

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

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.

Study Overview

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.

Study Type

Interventional

Enrollment (Actual)

353

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Okinawa
      • Tomishiro, Okinawa, Japan, 901-0243
        • Department of Cardiovascular Medicine, Tomishiro Central Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Anagliptin
Anagliptin 100 mg bid for 52 weeks. Can increase to 200 mg bid if needed.
Suiny 100 mg
Other Names:
  • Suiny
Active Comparator: Sitagliptin
Sitagliptin 50 mg qd for 52 weeks. Can increase to 100 mg qd if needed
Januvia 50 mg Glactiv 50 mg
Other Names:
  • Januvia
  • Glactiv

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Shinichiro Ueda, MD, PhD, Professor of Medicine, Department of Clinical Pharmacology & Therapeutics, University of the Ryukyus

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2015

Primary Completion (Actual)

January 1, 2018

Study Completion (Actual)

March 1, 2019

Study Registration Dates

First Submitted

December 30, 2014

First Submitted That Met QC Criteria

December 30, 2014

First Posted (Estimate)

January 5, 2015

Study Record Updates

Last Update Posted (Actual)

August 28, 2019

Last Update Submitted That Met QC Criteria

August 22, 2019

Last Verified

August 1, 2019

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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