Type 2 Diabetes
Conditions
Keywords
diabetes, insulin, byetta, glucose, blood sugar, metformin, A1c
Brief summary
This study is designed to look at how using glargine insulin with oral diabetes medications and exenatide may improve control of blood sugar levels and weight gain in type 2 diabetics. The main study will last 32 weeks. However, all participants completing 32 weeks will be invited to continue for another 24 weeks taking the insulin and oral medication and exenatide treatment. This extension comparing insulin and oral medication with insulin and oral medication and exenatide will look at the long term weight loss/gain and blood sugar level control effects of this new drug regimen. There is also a sub-study in the Clinical Research Center (CRC), which requires two 38-hour inpatient stays during the main study. This study offers the opportunity to study 24-hour blood sugar and metabolic patterns quantitatively.
Interventions
DRUGexenatide
5mcg twice a day, increasing to 10mcg twice a day for 24 weeks
DRUGplacebo
5mcg twice a day, increased to 10mcg twice a day for 24 weeks
Sponsors
Amylin Pharmaceuticals, LLC.
Eli Lilly and Company
Oregon Health and Science University
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or female patients with type 2 diabetes * Taking metformin at least 1000 mg daily plus a secretagogue, an alpha glucosidase inhibitor, a thiazolidinedione, or a single injection of any kind of insulin up to 0.4 units/kg daily for \> 3 months * Age range 30 to 70 years * Body mass index 25-45 kg/m2 * HbA1c 7.0 to 10.0% (or 7.0 to 8.5% if the second antihyperglycemic agent is insulin) * Less than 50% of randomized participants will have used insulin previously
Exclusion criteria
* Use of more than two antihyperglycemic agents within the last 3 months * Use of more than one daily injection of any kind of insulin in the last 3 months * Positive anti-GAD antibody (test required in screening) * Fasting C-peptide \<0.5 ng/mL (test required in screening) * Pregnancy (test required in screening if able to conceive) or lactation * Excessive use of alcohol or evidence of other form of drug dependency * Unwillingness or inability to grant informed consent * Unwillingness or inability to perform self-monitoring of blood glucose * Unwillingness or inability to inject insulin and/or inject exenatide * Serum creatinine \>1.3 mg/dL in women or 1.4 in men * Retinopathy which has required photocoagulation for treatment * Major active systemic illness (e.g. neoplastic disorder, symptomatic ischemic heart disease, congestive heart failure) that might interfere with performing the study protocol * Clinically significant gastrointestinal disorder including prior gastric or intestinal surgery for weight-control * Ongoing use of any drug (e.g. narcotic analgesic, tricyclic antidepressant) that might alter gastric emptying * Use prednisone or other systemic glucocorticoid drug in the last 3 months * Use of any drug for weight-control (e.g. sibutramine, phentermine, orlistat) in the last 3 months * Use of any unproven investigational drug within the last 3 months
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The Percentage of Intent to Treat Participants Randomized and Treated in Each Arm Who Had Lab-measured A1c <6.5% at 24 Weeks of Treatment | After 24 weeks of randomized treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Per Protocol Participants Randomized and Treated in Each Arm Who Had Lab-measured A1c <6.5% at 24 Weeks of Treatment | After 24 weeks of randomized treatment | efficacy criteria, 50% of per protocol participants reached A1c target of \<6.5% |
Countries
United States
Participant flow
Recruitment details
Recruitment: March 2007 - February 2009 Participant source: medical clinics, local communities
Pre-assignment details
There were 8 weeks of open-label exenatide use before enrollment into the randomized portion of the study to ensure patients ability to tolerate medication before adding insulin to the medication regimen.
Participants by arm
| Arm | Count |
|---|---|
| Exenatide Group Participants will receive exenatide as part of their diabetes treatment
exenatide : 5mcg twice a day, increasing to 10mcg twice a day for 24 weeks | 17 |
| Placebo Group Participants will receive placebo rather than exenatide as part of their diabetes treatment
placebo : 5mcg twice a day, increased to 10mcg twice a day for 24 weeks | 17 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Randomization (24 Weeks) | Withdrawal by Subject | 0 | 1 | 0 |
| Run -In (8 Weeks) | Adverse Event | 4 | 0 | 0 |
| Run -In (8 Weeks) | Withdrawal by Subject | 3 | 0 | 0 |
Baseline characteristics
| Characteristic | Exenatide Group | Placebo Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 2 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 15 Participants | 30 Participants |
| Sex: Female, Male Female | 9 Participants | 11 Participants | 20 Participants |
| Sex: Female, Male Male | 8 Participants | 6 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 21 / 38 | 15 / 17 | 10 / 17 | 11 / 14 | 12 / 17 |
| serious Total, serious adverse events | 0 / 38 | 0 / 17 | 0 / 17 | 0 / 14 | 0 / 17 |
Outcome results
Primary
The Percentage of Intent to Treat Participants Randomized and Treated in Each Arm Who Had Lab-measured A1c <6.5% at 24 Weeks of Treatment
Time frame: After 24 weeks of randomized treatment
Population: Intent to treat. All participants randomized to treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exenatide Group | The Percentage of Intent to Treat Participants Randomized and Treated in Each Arm Who Had Lab-measured A1c <6.5% at 24 Weeks of Treatment | 47 percentage of participants |
| Placebo Group | The Percentage of Intent to Treat Participants Randomized and Treated in Each Arm Who Had Lab-measured A1c <6.5% at 24 Weeks of Treatment | 12 percentage of participants |
Secondary
The Percentage of Per Protocol Participants Randomized and Treated in Each Arm Who Had Lab-measured A1c <6.5% at 24 Weeks of Treatment
efficacy criteria, 50% of per protocol participants reached A1c target of \<6.5%
Time frame: After 24 weeks of randomized treatment
Population: Per protocol, all participants who completed treatment
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Exenatide Group | The Percentage of Per Protocol Participants Randomized and Treated in Each Arm Who Had Lab-measured A1c <6.5% at 24 Weeks of Treatment | 50 percentage of participants | 0.27 |
| Placebo Group | The Percentage of Per Protocol Participants Randomized and Treated in Each Arm Who Had Lab-measured A1c <6.5% at 24 Weeks of Treatment | 12 percentage of participants | — |