Effects of Fimasartan on Insulin Secretion in Type 2 Diabetic Patients

Study Overview
=================
Brief Summary
-----------------
This study was designed to evaluate the effect of ARB in improving insulin secretion in patients with type 2 diabetes. The investigators also aimed to evaluate if there are potential synergisms between ARB and DPP4 inhibitors in improving insulin secretion and urinary albumin secretion in diabetic patients.

Detailed Description
-----------------
Angiotensin II has been reported to insulin secretion in beta cells. Angiotensin II indirectly improves insulin secretion in beta cells via vasoconstriction and reduced islet blood flow. Chronic exposure to high glucose or high fat increases expression of AT1R (angiotensin type 1 receptor), leading to reactive oxidative stresses, inflammation, and apoptosis in beta cells, finally decreased insulin formation and secretion. Some studies showed the beneficial effect of blocking AT1R on insulin secretion and beta cell proliferation in animal models using angiotensin receptor blocker (ARB). Furthermore, 26 weeks of valsartan treatment improved insulin secretion in humans with impaired glucose regulation.

Official Title
-----------------
Effects of Fimasartan on Insulin Secretion, and Interaction With DPP4 Inhibitors in Patients With Type 2 Diabetes

Conditions
-----------------
Diabetes Mellitus, Hypertension

Intervention / Treatment
-----------------
* Drug: Fimasartan
* Drug: Amlodipine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Aged 20 80 years Type 2 diabetic patients diagnosed more than 6 months ago HbA1c ≤8.5% at screening No change of OAD within the 3 months before screening SBP <140 mmHg and DBP <90 mmHg with anti-hypertensive drug at screening SBP ≥140 mmHg or DBP ≥80 mmHg without anti-hypertensive drug at screening Exclusion Criteria: Type 1 diabetic patients or active insulin treatment at screening Treatment with ARB or ACEi within 1 month prior to screening Uncontrolled hypertension with SBP >170 mmHg or DBP >100 mmHg Pregnancy or lactation Elevated liver enzyme (AST or ALT > 3 times the UNL) or elevated serum Cr (≥1.5 mg/dL in men and 1.4 mg/dL in women)

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fimasartan<br>Expreimental drug is fimasartan. | Drug: Fimasartan<br>* 16 weeks of fimasartan vs. amlodipine followed by 2 weeks of wash-out period, then crossover<br>|
| Active Comparator: Amlodipine<br>Active comparator is amlodipine. | Drug: Amlodipine<br>* 16 weeks of fimasartan vs. amlodipine followed by 2 weeks of wash-out period, then crossover<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulinogenic index |  | 16 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HOMA β-cell function |  | 16 week | 
| Insulin resistance |  | 16 week | 
| Urinary albumin creatinine ratio, urinary protein creatinine ratio |  | 16 week |