Safety and Efficacy of Exenatide Once Weekly Versus Liraglutide in Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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No head to head comparisons between exenatide once weekly and liraglutide have been performed. Therefore, the purpose of this study is to compare exenatide once weekly to once-daily liraglutide with regard to HbA1c, body weight, subject-reported outcomes, and other clinical benefits. The study includes a 26-week treatment period and a safety follow-up visit 10 weeks after the final study drug dose.

Official Title
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Safety and Efficacy of Exenatide Once Weekly Versus Liraglutide in Subjects With Type 2 Diabetes and Inadequate Glycemic Control Treated With Lifestyle Modification and Oral Antidiabetic Medications

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: exenatide once weekly
* Drug: liraglutide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with type 2 diabetes Have suboptimal glycemic control as evidenced by an HbA1c measurement at study start 7.1% and 11.0%, inclusive Have a body mass index (BMI) ≤45 kg/m^2 Have been treated with lifestyle modification (diet and exercise) and with one of the following single oral antidiabetic agents (OADs) or combinations of OADs administered at maximum tolerated dose: metformin SU metformin plus an SU metformin plus pioglitazone Exclusion Criteria: Have any contraindication, allergy, or hypersensitivity for the study drug (exenatide once weekly or liraglutide), exenatide twice daily, the OAD(s) being used, or the excipients contained in these agents If taking metformin and have a contraindication to metformin use Have been treated within 8 weeks of study start with systemic glucocorticoid therapy by oral, intravenous, intra-articular, or intramuscular route Have been treated with drugs that promote weight loss (e.g., Xenical® [orlistat], Meridia® [sibutramine], Acomplia® [rimonabant], Acutrim® [phenylpropanolamine], or similar over-the-counter medications) within 3 months of study start Have taken any of the following excluded medications for more than 1 week within the 3 months prior to study start, or have taken any of the following excluded medications within 1 month prior to study start: Insulin Alpha-glucosidase inhibitors (e.g., Glyser® [miglitol] or Precose® [acarbose]) Meglitinides (e.g., Prandin® [repaglinide] or Starlix® [nateglinide]) Avandia® (rosiglitazone) Dipeptidyl peptidase (DPP)-4 inhibitors (e.g., Januvia™ [sitagliptin], Galvus® [vildagliptin], Onglyza™ [saxagliptin]) Symlin® (pramlintide acetate) Have donated blood within 30 days prior to study start or have had a blood transfusion or severe blood loss within 3 months prior to study start Have at any time, including a clinical trial, taken exenatide once weekly, exenatide twice daily, liraglutide, or any other GLP-1 receptor agonist or GLP-1 analog Are currently enrolled in, or discontinued within the last 3 months or longer if required by local guidelines, from a clinical trial involving use of an investigational drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study Have previously been screen-failed from this study for any reason If a subject discontinues metformin, sulfonylurea, or pioglitazone prior to screening, the subject can be included if they discontinued the medication (whether alone or as component of combined medication) according to a specific schedule.

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 weekly<br>|
| Active Comparator: 2<br> | Drug: liraglutide<br>* subcutaneous injection, forced titration to 1.8mg, once daily<br>* Other names: Victoza;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c From Baseline to Week 26 | Change in HbA1c from baseline to the treatment endpoint at Week 26. | Baseline, Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Achieving HbA1c <7.0% at Week 26 | Percentage of patients achieving HbA1c <7.0% at treatment endpoint at Week 26. | Baseline, Week 26 | 
| Change in Fasting Serum Glucose From Baseline to Week 26 | Change in fasting serum glucose from baseline to the treatment endpoint at Week 26. | Baseline, Week 26 | 
| Change in Body Weight From Baseline to Week 26 | Change in body weight from baseline to the treatment endpoint at Week 26. | Baseline, Week 26 | 
| Change in Total Cholesterol From Baseline to Week 26 | Change in total cholesterol from baseline to the treatment endpoint at Week 26. | Baseline, Week 26 | 
| Change in High-Density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26 | Change in HDL-C from baseline to the treatment endpoint at Week 26. | Baseline, Week 26 | 
| Ratio of Fasting Triglycerides at Week 26 to Baseline | Ratio of fasting triglycerides (measured in mmol/L) treatment endpoint at Week 26 to baseline. Log(Postbaseline fasting triglycerides) - log(Baseline fasting triglycerides); change from baseline to the treatment endpoint at Week 26 is presented as ratio of Week 26 to baseline. | Baseline, Week 26 | 
| Change in Systolic Blood Pressure (SBP) From Baseline to Week 26 | Change in SBP from baseline to the treatment endpoint at Week 26. | Baseline, Week 26 | 
| Change in Diastolic Blood Pressure (DBP) From Baseline to Week 26 | Change in DBP from baseline to the treatment endpoint at Week 26. | Baseline, Week 26 | 
| Assessment of Event Rate of Treatment-emergent Hypoglycemic Events | Major hypoglycemia: any episode with symptoms consistent with hypoglycemia that resulted in loss of consciousness or seizure with prompt recovery in response to administration of glucagon or glucose OR documented hypoglycemia (blood glucose <3.0 mmol/L [54 mg/dL]) and required the assistance of another person. Minor hypoglycemia: any sign or symptom associated with hypoglycemia that is either self-treated by the patient or resolves on its own AND has a concurrent finger stick blood glucose <3.0 mmol/L (54 mg/dL) and not classified as major hypoglycemia. Event rate per subject year was calculated for each subject: (number of events observed from a subject/exposure from a subject)*365.25 where exposure = last post-baseline visit date - baseline visit date. Mean and Standard Error were then derived from ITT. | Baseline to 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, liraglutide, Victoza, Amylin, Lilly