Efficacy of Once-Weekly Exenatide Versus Once or Twice Daily Insulin Detemir in Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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The purpose of this study is to compare the effects of exenatide once weekly (QW) and insulin detemir with respect to glycemic control, body weight, lipids, safety, tolerability, and patient reported outcomes.

Official Title
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Efficacy of Once-Weekly Exenatide Versus Once or Twice Daily Insulin Detemir in Patients With Type 2 Diabetes Treated With Metformin Alone or in Combination With Sulphonylurea

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: exenatide once weekly
* Drug: insulin detemir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have suboptimal glycaemic control as evidenced by an HbA1c 7.1% to 10.0%, inclusive Have a body mass index (BMI) of 25 kg/m2 to 45 kg/m2, inclusive Are receiving metformin at a stable dose (consistent with country specific requirements) of a minimum of 1000mg for at least 3 months prior to start start OR are receiving metformin at a minimum dose (consistent with country specific requirements) of 1000mg and sulphonylurea (as separate medications not as a fixed dose combination) at stable doses for 3 months prior to study start Exclusion Criteria: Have any contraindication for the OAD that they have been using Have a known allergy or hypersensitivity to insulin detemir, exenatide or excipients contained in these agents Have been treated within 4 weeks of screening with systemic glucocorticoid therapy by oral, intravenous (IV) or intramuscular (IM) route, or are regularly treated with potent, inhaled intranasal steroids that are known to have a high rate of systemic absorption. Exceptions to this criterion include patients who are receiving glucocorticoid therapy for corticotropic hypopituitary deficiency (e.g. Addison disease) Have been treated with drugs that promote weight loss, within 3 months of screening Have been treated for longer than 2 weeks with any of the following excluded medications within 3 months prior to screening: insulin, alpha-glucosidase, Byetta® (exenatide BID formulation), thiazolidinediones (TZD), dipeptidyl peptidase (DPP)-4 inhibitors Have previously completed or withdrawn from this study or any other study investigating exenatide QW Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an off-label use of an investigational drug or device (other than the study drug/device used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study

Ages Eligible for Study
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Minimum Age: 18 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: exenatide once weekly<br>* subcutaneous injection, 2mg, once a week<br>|
| Active Comparator: 2<br> | Drug: insulin detemir<br>* subcutaneous injection, with dosage titrated according to the determir label and published titration schedule, once or twice a day<br>* Other names: Levemir;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Achieving Glycosylated Hemoglobin (HbA1c) Concentration ≤7.0% With Weight Loss (≥1.0 kg) at Endpoint (Week 26) | The primary endpoint is the percentage of patients achieving HbA1c concentration ≤7.0% with weight loss (≥1.0 kg) at endpoint. The last post-baseline measurement set of both non-missing HbA1c concentration and weight (measured at the same time point, i.e. visit) is used as endpoint value. Patients who do not have a baseline weight measurement, have a protocol violation of baseline HbA1c <=7.0%, and/or have missing post-baseline measurements for HbA1c concentration and/or weight, are included in the analysis as non-responders regarding the primary objective. | Baseline, Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Who Have Achieved HbA1c ≤7.4% With Weight Loss (≥1.0 kg) at Endpoint (Week 26) | Percentage of patients who have achieved HbA1c ≤7.4% with weight loss (≥1.0 kg) at endpoint (Week 26) | Baseline, Week 26 | 
| Change in HbA1c From Baseline to Week 26 | Change in HbA1c from baseline to week 26 | Baseline, Week 26 | 
| Change in Body Weight From Baseline to Week 26 | Change in body weight from baseline to week 26 | Baseline, Week 26 | 
| Percentage of Patients Achieving HbA1c ≤7.4% at Endpoint | Percentage of patients who have achieved HbA1c ≤.7.4% at endpoint | Week 26 | 
| Percentage of Patients Achieving ≤7.0% at Endpoint | Percentage of patients achieving ≤7.0% at endpoint. | Week 26 | 
| Percentage of Patients Achieving ≤6.5% at Endpoint | Percentage of patients achieving HbA1c ≤6.5% at endpoint | Week 26 | 
| Change in Fasting Serum Glucose From Baseline to Endpoint (Week 26). | Change in fasting serum glucose from baseline to endpoint (Week 26). | Baseline, Week 26 | 
| Changes in Systolic Blood Pressure From Baseline to Week 26 | Change in systolic blood pressure from baseline to Week 26 | Baseline, Week 26 | 
| Change in Diastolic Blood Pressure From Baseline to Week 26. | Change in diastolic blood pressure from baseline to week 26. | Baseline, Week 26 | 
| Change in Total Cholesterol From Baseline to Endpoint (Week 26). | Change in total cholesterol from baseline to endpoint (week 26). | Baseline, Week 26 | 
| Change in High-density Lipoprotein (HDL) Cholesterol From Baseline to Endpoint (Week 26). | Change in High-density lipoprotein (HDL) cholesterol from baseline to endpoint (week 26). | Baseline, Week 26 | 
| Change in Triglycerides From Baseline to Endpoint (Week 26). | Change in triglycerides from baseline to endpoint (week 26). | Baseline, Week 26 | 
| Hypoglycemia Rate Per Year | All confirmed hypoglycemia episodes defined as either minor (any time a patient feels that he or she is experiencing a sign or symptom associated with hypoglycaemia and blood glucose (BG) <3.0 mmol/L (54 mg/dL)) or major (any hypoglycaemic episode with symptoms consistent with hypoglycaemia, resulting in loss of consciousness or seizure, and shows prompt recovery in response to administration of glucagon or glucose, or BG measurement < 3.0mmol/L is available and the patient is not capable of self-treating were taken into account. | Baseline, Week 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes, exenatide once weekly, Byetta, insulin detemir, Levemir, Amylin, Lilly