Effect of Exenatide Plus Metformin vs. Insulin Aspart Plus Metformin on Glycemic Control and Hypoglycemia in Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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This study in Germany is designed to compare the effects of twice-daily exenatide plus metformin and twice-daily premixed human insulin aspart plus metformin with respect to glycemic control, as measured by HbA1c, combined with the percentage of patients with at least one treatment-emergent hypoglycemic episode. Patients will be treated with study therapy for approximately 26 weeks.

Official Title
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Effect of Exenatide Plus Metformin vs. Premixed Human Insulin Aspart Plus Metformin on Glycemic Control and Hypoglycemia in Patients With Inadequate Control of Type 2 Diabetes on Oral Antidiabetic Treatment

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: exenatide twice daily (BID)
* Drug: premixed insulin aspart twice daily (BID)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have been treated with diet and exercise and a stable, maximally tolerated dose of immediate-release or extended-release metformin, or the combination of metformin (any dosage) with sulfonylurea/meglitinides for at least 3 months prior to study start Have not received thiazolidinediones, or alpha-glucosidase inhibitors for longer than 2 weeks within 3 months prior to study start, and have not received any insulin formulation for more than 14 days (other than in emergency situations) and within 14 days prior to study start Have an HbA1c between 6.5% and 10.0%, inclusive Have a body mass index (BMI) between 25 kg/m^2 and 40 kg/m^2, inclusive Exclusion Criteria: Have type 1 diabetes or known latent autoimmune diabetes in adults Are receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical and inhaled preparations) or have received such therapy within 2 weeks prior to study start Are receiving treatment for gastrointestinal disease with a drug directly affecting gastrointestinal motility (e.g., metoclopramide, cisapride, and chronic macrolide antibiotics) Have used any prescription drug to promote weight loss within 3 months prior to study start Have received treatment within 30 days prior to study start with a drug that has not received regulatory approval for any indication at the time of study entry Have previously completed or withdrawn from this study or any other study investigating exenatide or GLP-1 analogs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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: Exenatide Twice Daily (BID)<br> | Drug: exenatide twice daily (BID)<br>* subcutaneous injection (5 mcg or 10 mcg), twice a day<br>* Other names: Byetta;|
| Active Comparator: Premixed Insulin Aspart Twice Daily (BID)<br> | Drug: premixed insulin aspart twice daily (BID)<br>* subcutaneous injection (titrated appropriately), twice a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Glycosylated Hemoglobin (HbA1c) | Change in HbA1c from baseline after 26 weeks of treatment (i.e., HbA1c at week 26 minus HbA1c at week 0) | Baseline and 26 weeks | 
| Incidence of Hypoglycemia (Percentage of Participants With at Least One Hypoglycemic Episode) | Risk for first hypoglycemic episode (blood glucose <=3.9 mmol/L or severe episode) to occur up to week 26 | 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Achieving HbA1c Target of < 6.5% | Percentage of subjects achieving HbA1c target of < 6.5% at the end of study (week 26) [i.e., number of subjects who achieved HbA1c < 6.5% divided by total number of subjects times 100%]. | 26 weeks | 
| Percentage of Subjects Achieving HbA1c Target of < 7.0% | Percentage of subjects achieving HbA1c target of < 7.0% at the end of study (week 26) [i.e., number of subjects who achieved HbA1c < 7.0% divided by total number of subjects times 100%]. | 26 weeks | 
| Incidence of Hypoglycemic Episodes [Blood Glucose <= 3.0 mmol/L or Severe] (Percentage of Subjects Who Experienced at Least One Treatment-emergent Hypoglycemic Episode During the 26-week Treatment Period) | Risk for the first hypoglycemic episode to occur up to Week 26 (percentage of subjects who experienced at least one treatment-emergent hypoglycemic episode during the 26-week treatment period)[ i.e., number of subjects experiencing at least one hypoglycemic episode divided by total number of subjects times 100%] | 26 weeks | 
| Incidence of Nocturnal Hypoglycemia (Percentage of Subjects Who Experienced at Least One Episode of Nocturnal Hypoglycemia During the 26 Week Treatment Period) | Risk for first nocturnal (night-time) hypoglycemic episode to occur up to week 26 (percentage of subjects who experienced at least one episode of nocturnal hypoglycemia during the 26 week treatment period) [i.e., number of subjects who experienced nocturnal hypoglycemia divided by total number of subjects times 100%]. | 26 weeks | 
| 7 Point Self-monitored Blood Glucose (SMBG) Profiles | 7-point self-monitored blood glucose profiles at baseline and the end of the study, measured at 7 times during the day (pre-breakfast, 2 hours post-breakfast, pre-lunch, 2 hours post-lunch, pre-dinner, 2 hours post-dinner, and 3:00am). | Baseline and 26 weeks | 
| Blood Lipid Levels | Total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol (calculated), and triglyceride levels at baseline (week 0) and the end of the study (week 26) | Baseline and 26 weeks | 
| Change in Body Weight | Change in body weight from baseline after 26 weeks of treatment (i.e., body weight at week 26 minus body weight at week 0) | Baseline and 26 weeks | 
| Change in Body Mass Index (BMI) | Change in BMI from baseline after 26 weeks of treatment (i.e., BMI at week 26 minus BMI at week 0) | Baseline and 26 weeks | 
| Patient Reported Outcomes: Diabetes Treatment Satisfaction Questionnaire (DTSQ) | Total DTSQ treatment satisfaction score at baseline (week 0) and after 26 weeks of treatment (LOCF). Total DTSQ treatment satisfaction score is derived as sum score of the individual components 1 and 4-8 of the DTSQ questionnaire. Each component is scored on a scale of 0 (worst case) to 6 (best case). Higher values represent higher treatment satisfaction. | Baseline and 26 weeks | 
| Patient Reported Outcomes: Quality of Life (SF-12) | SF-12 Physical and Mental Component Summary Scores at baseline (week 0) and after 26 weeks of treatment (LOCF). SF-12 Physical and Mental Component Summary Scores are normalized scores ranging from 0 (worst case) to 100 (best case), and are derived from responses to 12 questions. Scores > 50 indicate an above-average health status. | Baseline and 26 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes, exenatide, Byetta, Amylin, Lilly