Atmeg (Atorvastatin and Omega-3 Combination) and Carotid Atherosclerosis in Patients With Type 2 Diabetes and Combined Dyslipidemia

Study Overview
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Brief Summary
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This is a randomized controlled study to assess the effect of atorvastatin and omega 3 combination therapy compared with atorvastatin and ezetimibe combination therapy in Korean T2DM patients with asymptomatic atherosclerosis.

Detailed Description
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In patients with type 2 diabetes with atherosclerotic combined dyslipidemia, the effect of atorvastatin and omega 3 combination on the progression of carotid intima media thickness and carotid artery plaque will be evaluated by 3D carotid ultrasound.

Official Title
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Effect of Atorvastatin and Omega 3 Combination Therapy on Carotid Atherosclerosis Estimated by 3D Ultrasound in Patients With Type 2 Diabetes and Combined Dyslipidemia

Conditions
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Dyslipidemias, Atherosclerosis, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Omega 3-Atorvastatin
* Drug: Omega 3-Atorvastatin
* Drug: Atorvastatin-Ezetimibe


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes under treatment with HbA1c 6.0-10.0% at screening visit Male or female of 20 years or over Mixed dyslipidemia under moderate-intensity statin: triglyceride ≥200 mg/dL, HDL-cholesterol ≤50 mg/dL, LDL-cholesterol ≥100 mg/dL moderate-intensity statin: atorvastatin 10-20mg, rosuvastatin 5mg, simvastatin 20-40mg, pravastatin 40-80mg, lovastatin 40mg, fluvastatin XL 80mg, fluvastatin 40mg bid, pitavastatin 2-4mg Identified carotid artery plaque: carotid intima-media thickness (cIMT) ≥ 1.5 mm Asymptomatic patients without history of angina, myocardial infarction, or cerebral infarction Creatinine ≤1.8 mg/dL Exclusion Criteria: Dyslipidemia which requires other therapy: triglyceride ≥500 mg/dL or LDL-cholesterol ≥190 mg/dL Uncontrolled hypertension: SBP >180 mmHg or DBP >110 mmHg Severe renal dysfunction: eGFR <30 mL/min/1.73m2 AST/ALT >120/120 or chronic liver disease Pregnant or childbearing woman who does not have enough contraception Changes of medication related to chronic diseases (diabetes, hypertension, dyslipidemia, etc.) within 3 months Usage of dyslipidemia therapy other than statin

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atmeg with Omethyl Cutielet<br>Atmeg: 2 capsules daily (1 capsule containes atorvastatin 10 mg and Omega-3 1000 mg) Omethyl Cutielet: Omega-3 2000mg (920mg as EPA ethyl ester, 760mg as DHA ethyl ester) once daily | Drug: Omega 3-Atorvastatin<br>* Atmeg 2 capsules with 1 pack of Omethyl cutielet<br>* Other names: Atmeg-Omethyl cutielet;|
| Active Comparator: Atmeg<br>Atmeg: 2 capsules daily (1 capsule containes atorvastatin 10 mg and Omega-3 1000 mg) | Drug: Omega 3-Atorvastatin<br>* Atmeg 2 capsules<br>* Other names: Atmeg;|
| Active Comparator: ezetimibe/atorvastatin 10/20<br>1 tablet once daily (atorvastatin 20mg with ezetimibe 10mg) | Drug: Atorvastatin-Ezetimibe<br>* ezetimibe/atorvastatin 10/20 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Volume of carotid artery plaque | measured by 3D ultrasound imaging | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Carotid intima media thickness |  | 24 weeks | 
| Coronary artery stenosis | Severity of coronary artery stenosis percent | 24 weeks | 
| Plaque characteristics Plaque characteristics Plaque characteristics Plaque characteristics | changes of non-calcified plaque volume (mm3) | 24 weeks | 
| Coronary artery calcium score | 0: No calcification of artery [higher scores implies worsening] | 24 weeks | 
| Glucose homeostasis | changes of HbA1c (%) | 24 weeks | 
| Lipid metabolism | TG concentration, HDL-cholesterol concentration | 24 weeks | 
| Bioelectrical Impedance Analysis | Body composition of fat mass (kg) | 24 weeks | 
| Proteinuria | albumin-to-creatinine ratio (mg/g) | 24 weeks | 
| Changes of gut microbiota | measured by 16S rRNA or metagenome sequencing, comparing the composition or each phylum/genus/species | 24 weeks |