Type 2 Diabetes
Conditions
Keywords
type 2 diabetes, obesity
Brief summary
Exenatide has been shown to result in better glycemic control in type II diabetes patients. Obesity and diabetes are states of increased inflammation; exenatide is expected to lead to decreased inflammation by virtue of better glycemic control and weight loss. The purpose of this study is to determine if the addition of Exenatide to diabetic patients will reduce the requirements of insulin particularly the short acting insulin. Exenatide may also lead to decreased inflammation by virtue of better glycemic control and weight loss, or an independent effect.
Interventions
DRUGexenatide 5 mcg
exenatide 5 mcg
DRUGexenatide 10 mcg
exenatide 10 mcg
DRUGplacebo
saline sq
Sponsors
Amylin Pharmaceuticals, 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 20-75 years of age inclusive. * Type 2 diabetes * On insulin therapy * HbA1c ≥7.5% and ≤ 9% * BMI ≥ 30 kg/m2 * Subjects on statins, ACE inhibitors, metformin, 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 study.
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) * Use of DPP4 inhibitors. * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fasting Insulin | after 24 hours fast at baseline and 12 weeks | To compare the fasting insulin level at the end of 12 weeks in patients on exenatide subcutaneously twice daily (5 or 10 mcg/injection) as compared to controls in insulin treated obese type 2 diabetic patients. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Weight | value at 12 weeks minus value at baseline | To compare the body weight at the end of 12 weeks in patients on exenatide subcutaneously twice daily (5 or 10 mcg/injection) as compared to controls in insulin treated obese type 2 diabetic patients |
| HbA1c | value at 12 weeks minus value at baseline | To compare the HbA1c at the end of 12 weeks in patients on exenatide subcutaneously twice daily (5 or 10 mcg/injection) as compared to controls in insulin treated obese type 2 diabetic patients. |
| Intranuclear NFκB Binding Activity | measured after 6 hours of a single dose of placebo or exenatide treatment for value measured at 12 weeks minus baseline | Measured by a gel shift assay showing the NFKB and Oct-1 binding to the doublestranded oligonucleotide containing the NFKB DNA binding site in Exenatide group and placebo group |
Countries
United States
Participant flow
Pre-assignment details
The exenatide 10mcg group started on 5mcg for a single dose study (samples collected were at 0, 2, 4, and 6 hours)
Participants by arm
| Arm | Count |
|---|---|
| Exenatide 10 mcg exenatide 5mcg and then exenatide 10 mcg | 12 |
| Placebo placebo
placebo: saline sq | 12 |
| Total | 24 |
Baseline characteristics
| Characteristic | Total | Exenatide 10 mcg | Placebo |
|---|---|---|---|
| Age, Continuous | 55 years STANDARD_DEVIATION 3 | 56 years STANDARD_DEVIATION 3 | 54 years STANDARD_DEVIATION 4 |
| BMI | 39.5 kg/m² STANDARD_DEVIATION 1.8 | 39.8 kg/m² STANDARD_DEVIATION 2 | 39.1 kg/m² STANDARD_DEVIATION 1.6 |
| Fasting Blood Glucose | 133 mg/dl STANDARD_DEVIATION 15 | 139 mg/dl STANDARD_DEVIATION 17 | 128 mg/dl STANDARD_DEVIATION 13 |
| FFA | 0.66 mM STANDARD_DEVIATION 0.08 | 0.69 mM STANDARD_DEVIATION 0.07 | 0.64 mM STANDARD_DEVIATION 0.08 |
| HbA1c | 8.55 % STANDARD_DEVIATION 0.4 | 8.6 % STANDARD_DEVIATION 0.4 | 8.5 % STANDARD_DEVIATION 0.3 |
| Race and Ethnicity Not Collected | 0 Participants | — | — |
| Sex/Gender, Customized Sex/Gender Baseline | 0 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 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
Fasting Insulin
To compare the fasting insulin level at the end of 12 weeks in patients on exenatide subcutaneously twice daily (5 or 10 mcg/injection) as compared to controls in insulin treated obese type 2 diabetic patients.
Time frame: after 24 hours fast at baseline and 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide 10 mcg | Fasting Insulin | At Baseline | 12.7 μU/mL | Standard Error 2.8 |
| Exenatide 10 mcg | Fasting Insulin | At 12 weeks | 16.4 μU/mL | Standard Error 3.2 |
| Placebo | Fasting Insulin | At Baseline | 13.1 μU/mL | Standard Error 3.1 |
| Placebo | Fasting Insulin | At 12 weeks | 13.9 μU/mL | Standard Error 5.9 |
Secondary
HbA1c
To compare the HbA1c at the end of 12 weeks in patients on exenatide subcutaneously twice daily (5 or 10 mcg/injection) as compared to controls in insulin treated obese type 2 diabetic patients.
Time frame: value at 12 weeks minus value at baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exenatide 10 mcg | HbA1c | -1.2 percent | Standard Error 0.5 |
| Placebo | HbA1c | -0.5 percent | Standard Error 0.3 |
Secondary
Intranuclear NFκB Binding Activity
Measured by a gel shift assay showing the NFKB and Oct-1 binding to the doublestranded oligonucleotide containing the NFKB DNA binding site in Exenatide group and placebo group
Time frame: measured after 6 hours of a single dose of placebo or exenatide treatment for value measured at 12 weeks minus baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exenatide 10 mcg | Intranuclear NFκB Binding Activity | 26 % ratio of NFKB/Oct-1 | Standard Error 7 |
| Placebo | Intranuclear NFκB Binding Activity | 0 % ratio of NFKB/Oct-1 | Standard Error 7 |
Secondary
Weight
To compare the body weight at the end of 12 weeks in patients on exenatide subcutaneously twice daily (5 or 10 mcg/injection) as compared to controls in insulin treated obese type 2 diabetic patients
Time frame: value at 12 weeks minus value at baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exenatide 10 mcg | Weight | 0 lbs | Standard Error 20 |
| Placebo | Weight | 3 lbs | Standard Error 18 |