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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Anagliptin | Active Comparator | Anagliptin 100 mg bid for 52 weeks. Can increase to 200 mg bid if needed. |
|
| Sitagliptin | Active Comparator | Sitagliptin 50 mg qd for 52 weeks. Can increase to 100 mg qd if needed |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Anagliptin | Drug | Suiny 100 mg |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in low-density lipoprotein cholesterol | 52-weeks | |
| Change in glycated hemoglobin | 52-weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change in fasting glucose | 52-weeks | |
| Change in fasting insulin | 52-weeks | |
| Change in 1.5-Anhydro-D-glucitol |
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Inclusion Criteria:
(*) cardiovascular risk factors were any of following conditions
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Shinichiro Ueda, MD, PhD | Professor of Medicine, Department of Clinical Pharmacology & Therapeutics, University of the Ryukyus | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Cardiovascular Medicine, Tomishiro Central Hospital | Tomishiro | Okinawa | 901-0243 | Japan |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32539832 | Derived | 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. | |
| 31733647 |
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| Sitagliptin |
| Drug |
Januvia 50 mg Glactiv 50 mg |
|
|
| 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 |
| Derived |
| 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. |
| 31189978 | Derived | 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. |
| 29435776 | Derived | 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. |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D003327 | Coronary Disease |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| C583175 | anagliptin |
| D000068900 | Sitagliptin Phosphate |
| ID | Term |
|---|---|
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011719 | Pyrazines |
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