The Effect of LINAGLIPTIN on Inflammation, Oxidative Stress and Insulin Resistance in Obese Type 2 Diabetes Subjects

Study Overview
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Brief Summary
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This is a single center, prospective randomized double blind, parallel and placebo controlled study to evaluate oxidative stress and inflammation before and after treatment with linagliptin for 12 weeks. We will also, testing whether Linagliptin is an insulin sensitizer.

Detailed Description
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This is a single center, prospective randomized double blind, parallel and placebo-controlled study to evaluate oxidative stress and inflammation before and after treatment with linagliptin for 12 weeks. The study enrolls type 2 patients with diabetes.

Official Title
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The Effect of TRADJENTA ® (LINAGLIPTIN) on Inflammation, Oxidative Stress and Insulin Resistance in Obese Type 2 Diabetes Subjects

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Linagliptin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 20-80 years inclusive. Type 2 diabetes BMI ≥30 kg/m2 Subjects on statins, ACE inhibitors, thiazolidinediones and antioxidants will be allowed as long as they are on stable doses of these compounds and the dosage in not changed during the course of study. HbA1c ≤ 8.0% Exclusion Criteria: - Use of GLP-1 agonists or DPP-IV therapy in the last 3 months. History of Pancreatitis. Risk for pancreatitis, i.e., history of gallstones, alcohol abuse, and hypertriglyceridemia. Subjects who are taking antiplatelet or anticoagulant medications will be excluded from the fat biopsy portion of the study. Coronary event or procedure (myocardial infarction, unstable angina, coronary artery bypass, surgery or coronary angioplasty) in the previous four weeks Hepatic disease (liver function tests more than 3 times the upper limit of normal) Renal impairment (serum eGFR <30 ml/min) Any other life-threatening, non-cardiac disease Uncontrolled hypertension (BP > 160/100 mm of Hg) Congestive Heart Failure class III or IV. Use of an investigational agent or therapeutic regimen within 30 days of study Participation in any other concurrent clinical trial

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Patients will be treated for 12 weeks with placebo once daily | Drug: Placebo<br>* matching placebo giving orally daily<br>|
| Active Comparator: Linagliptin 5mg per day<br>Patients will be treated for 12 weeks with Linagliptin 5mg once daily. | Drug: Linagliptin<br>* 5 mg daily oral tablets of linagliptin<br>* Other names: TRADJENTA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| JNK-1 Protein in MNC | JNK-1 protein in MNC before and after linagliptin use as compared to placebo. | Week 0, Week 2, Week 4, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IL-1β mRNA Levels | Comparing IL-1B between Linagliptin group and placebo group based on the PCR test, between week 0 and week 12. | Week 0, Week 2, Week 4, Week 12 | 
| Oxidative Stress (as ROS Generation Level) | oxidative stress (ROS generation level) following linagliptin. ROS generation measurement by chemiluminescence of PMN cells | Week 0, Week 2, Week 4, Week 12 | 
| Insulin Sensitivity by Hyperinsulinemic-euglycemic Clamp | Insulin sensitivity is measured with HE clamp. Glucose Infusion Rate was titrated to maintain blood glucose concentration at the fasting glucose level. Plasma samples for glucose was obtained at 10-minute intervals starting 30 minutes before the clamp, to quantitate rates of whole-body glucose disposal. Difference from baseline at 12 weeks is calculated and compared to placebo arm | At baseline and week 12 |