Exenatide Plus Pioglitazone Versus Insulin in Poorly Controlled T2DM

Study Overview
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Brief Summary
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To compare efficacy, safety and durability of combination therapy with pioglitazone plus GLP-1 RA versus basal bolus insulin in poorly controlled T2DM patients on metformin plus sulfonylurea

Detailed Description
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poorly controlled (HbA1c >7.5%) T2DM patients (18-75 years of age) on maximal/near maximal dose of sulfonylurea plus metformin who otherwise are healthy will be randomized to receive: exenatide weekly injection (2 mg/week) glargine insulin plus insulin aspart which will be titrated to maintain HbA1c <7.0%

Official Title
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Efficacy and Durability of Glucagon Like Peptide 1 Receptor Agonists (GLP-1 RA)/Thiazolidinedione Versus Basal Bolus Insulin Therapy in Poorly Controlled Type 2 Diabetic Patients (T2DM) Patients on Sulfonylurea Plus Metformin

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Pioglitazone plus exenatide
* Drug: insulin glargine and insulin aspart


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: T2DM poorly controlled (HbA1c >7.5%) on metformin (>1700 mg/day) plus sulfonylurea Exclusion Criteria: type 1 diabetes (T1DM) patients receiving therapy with pioglitazone, GLP-1 RA and insulin abnormal kidney, liver or heart function patients with malignancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Combination Therapy<br>pioglitazone (actos) 30 mg per day and exenatide (bydureon) 2 mg per week | Drug: Pioglitazone plus exenatide<br>* pioglitazone will be started at 30 mg/day and bydureon at 2 mg/week<br>* Other names: actos and bydureon;|
| Active Comparator: Insulin Therapy<br>insulin glargine (lantus) will be started every morning and the dose will be weekly increase to achieve fasting plasma glucose (FPG) <110 mg/dl. and Aspart insulin will be started before meals and the dose is adjusted to maintain HbA1c <7.0% and postprandial plasma glucose (PPG) <140 mg/dl | Drug: insulin glargine and insulin aspart<br>* the dose will be escalated to maintain HbA1c <7.0%<br>* Other names: lantus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c | difference in HbA1c between the two treatment groups will be compared at 1 and at 3 years to determine efficacy and durability of each treatment | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| percentage of patients who achieve HbA1c <7.0% and <6.5% at 1 year and at 3 years |  | 3 years | 
| hypoglycemia rate | will be measured as absolute event rate per patient year of follow up | 3 years | 
| change in the FPG | change in FPG from time zero to 1 year and from baseline to 3 years in each treatment group | 3 years | 
| change in body weight | change in body weight from time zero to 1 year and to 3 years in each treatment group | 3 years |