The Effect of Januvia (Sitagliptin) on Oxidative Stress in Obese Type 2 Diabetic Subjects

Study Overview
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Brief Summary
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Sitagliptin is a new oral hypoglycemic anti-diabetic drug used either alone or in combination with metformin or a thiazolidinedione for control of type 2 diabetes mellitus. Sitagliptin has been shown to have fewer side effects in the control of blood glucose values. Obesity and diabetes are states of increased inflammation and can influence the free radicals and inflammatory markers (chemicals in the blood which increase due to inflammation in the body) and are also major risk factors for atherosclerotic disease. In this study we want to see the effect of sitagliptin on these markers. We believe that Sitagliptin may exert an anti-inflammatory effect in the human. The purpose of this study is to determine if the addition of sitagliptin to diabetic patients will provide added benefit. We believe that sitagliptin provides these added benefits by suppressing free radicals (charged substances that cause damage to the body) and inflammation.

Official Title
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The Effect of Januvia (Sitagliptin) on Oxidative Stress in Obese Type 2 Diabetic Subjects

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Januvia (Sitagliptin) 100 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females with age 20-75 years inclusive. Type 2 diabetes Males and Females BMI > 30 Subjects on statins, ACE inhibitors, thiazolidenediones 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. BP under control -No change required to BP medications HbA1c > 7% Exclusion Criteria: Coronary event or procedure (myocardial infarction, unstable angina, coronary artery bypass, surgery or coronary angioplasty) in the previous four weeks Pregnancy Hepatic disease (abnormal LFT's),Renal impairment (serum creatinine > 1.5), Participation in any other concurrent clinical trial Any other life-threatening, non-cardiac disease, Uncontrolled hypertension (BP > 160/100 mm of Hg) Congestive Heart Failure Use of an investigational agent or therapeutic regimen within 30 days of study Subjects on Exenatide, incretin or insulin therapy

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 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 |
| --- | --- |
| Active Comparator: Januvia 100mg<br>The first group will be started on 100 mg sitagliptin daily for 12 weeks | Drug: Januvia (Sitagliptin) 100 mg<br>* The first group will be started on 100 mg sitagliptin daily for 12 weeks<br>* Other names: januvia;|
| Placebo Comparator: placebo<br>will be placed on a placebo for 12 weeks. | Drug: Placebo<br>* will be placed on a placebo for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Reactive Oxygen Species (ROS) Generation by MNC, Protein and mRNA Expression of p47phox Subunit of NADPH Oxidase, in MNC's of Obese Type 2 Diabetic Patients |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Oxidative Stress From Baseline to 12 Weeks | To investigate that therapy with sitagliptin orally daily (100 mg) for 12 weeks decreases oxidized lipids (9-hydroxyoctadecadienoicacid (9-HODE) and 13-HODE) in plasma and F2-isoprostane in urine of obese type 2 diabetic patients Outcome measures given are calculated from the baseline - 12 weeks. | value at 12 weeks minus value at baseline |