Type 2 Diabetes
Conditions
Brief summary
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.
Interventions
DRUGJanuvia (Sitagliptin) 100 mg
The first group will be started on 100 mg sitagliptin daily for 12 weeks
DRUGPlacebo
will be placed on a placebo for 12 weeks.
Sponsors
Merck Sharp & Dohme LLC
University at Buffalo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | 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
| Measure | Time frame | Description |
|---|---|---|
| Change in Oxidative Stress From Baseline to 12 Weeks | value at 12 weeks minus value at baseline | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Januvia 100mg The first group will be started on 100 mg sitagliptin daily for 12 weeks
Januvia (Sitagliptin) 100 mg: The first group will be started on 100 mg sitagliptin daily for 12 weeks | 12 |
| Placebo will be placed on a placebo for 12 weeks.
Placebo: will be placed on a placebo for 12 weeks. | 10 |
| Total | 22 |
Baseline characteristics
| Characteristic | Januvia 100mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 54 years STANDARD_DEVIATION 4 | 53 years STANDARD_DEVIATION 3 | 53.5 years STANDARD_DEVIATION 3.5 |
| BMI | 35 kg/m^2 STANDARD_DEVIATION 1.5 | 35.4 kg/m^2 STANDARD_DEVIATION 1.3 | 35.2 kg/m^2 STANDARD_DEVIATION 1.4 |
| Fasting glucose | 135 mg/dL STANDARD_DEVIATION 13 | 148 mg/dL STANDARD_DEVIATION 23 | 140 mg/dL STANDARD_DEVIATION 18 |
| HbA1c | 7.6 percentage STANDARD_DEVIATION 0.4 | 7.9 percentage STANDARD_DEVIATION 0.3 | 7.7 percentage STANDARD_DEVIATION 0.3 |
| Sex: Female, Male Female | 6 Participants | 4 Participants | 10 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 12 | 0 / 10 |
| serious Total, serious adverse events | 0 / 12 | 0 / 10 |
Outcome results
Primary
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
Time frame: 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Januvia 100mg | 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 | TNF-alpha | -39 Percent change | Standard Error 10 |
| Januvia 100mg | 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 | TLR-2 | -35 Percent change | Standard Error 9 |
| Januvia 100mg | 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 | CCR-2 | -24 Percent change | Standard Error 8 |
| Januvia 100mg | 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 | JNK-1 | -19 Percent change | Standard Error 8 |
| Januvia 100mg | 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 | TLR-4 | -23 Percent change | Standard Error 11 |
| Januvia 100mg | 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 | IKK-beta | -17 Percent change | Standard Error 9 |
| Placebo | 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 | TLR-4 | 8 Percent change | Standard Error 5 |
| Placebo | 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 | CCR-2 | 6 Percent change | Standard Error 4 |
| Placebo | 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 | TNF-alpha | 12 Percent change | Standard Error 8 |
| Placebo | 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 | IKK-beta | 9 Percent change | Standard Error 8 |
| Placebo | 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 | TLR-2 | 3 Percent change | Standard Error 5 |
| Placebo | 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 | JNK-1 | 4 Percent change | Standard Error 7 |
Secondary
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.
Time frame: value at 12 weeks minus value at baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Januvia 100mg | Change in Oxidative Stress From Baseline to 12 Weeks | -0.13 mM | Standard Error 0.06 |
| Placebo | Change in Oxidative Stress From Baseline to 12 Weeks | -0.06 mM | Standard Error 0.08 |