Efficacy and Safety of Basal Insulin Glargine Combination With Exenatide Bid vs Aspart30 in T2DM

Study Overview
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Brief Summary
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Efficacy and Safety of Basal Insulin Glargine Combination with Exenatide bid vs Switching Premix Human Insulin to Aspart30 in T2DM with Inadequate Glycaemic Control on Premixed Human Insulin and Metformin: a Randomized, Open, Parallel trial.

Detailed Description
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This is a multicentre, open-label, randomized and parallel trial that will compare the efficacy and safety of basal insulin glargine combination with Exenatide bid vs. switching premix human insulin to aspart30 in type 2 diabetic patients with inadequate glycaemic control on premixed human insulin and metformin. Approximately 248 patients will be enrolled in the study from China and randomized in a 1:1 ratio to one of the 2 treatment arms: once-daily insulin glargine + twice-daily exenatide + metformin; or twice-daily aspart 30 + metformin. Study treatment will continue for 24 weeks. The primary efficacy measure is the change in HbA1c at 24 weeks. The study consists of 3 periods: a 1-week screening (period A), a 12-week run-in period (period B) and a 24-week treatment period (period C).

Official Title
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Efficacy and Safety of Basal Insulin Glargine Combination With Exenatide Bid vs Switching Premix Human Insulin to Aspart30 in T2DM With Inadequate Glycaemic Control on Premixed Human Insulin and Metformin: a Randomized, Open, Parallel Trial

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: glargine + exenatide
* Drug: aspart 30


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of informed consent Type 2 diabetic patients receiving twice-daily premixed human insulin 30 therapy ≥ 30 U/d and metformin with maximum tolerated dosage (≤ 1500mg/d) HbA1c > 8.0 % and < 11.0 % (HbA1c > 7.0 % and < 10.0% at randomization) Men and women (non-pregnant and using a medically approved birth-control method) aged ≥ 18 and ≤ 70 years BMI ≥ 23 and ≤ 35 kg/m2 Exclusion Criteria: Type 1 diabetes or other specific types of diabetes Pregnancy, preparation for pregnancy, lactation and women of child-bearing age incapable of effective contraception methods Uncooperative subject because of various reasons Abnormal liver function, glutamic-pyruvic transaminase (ALT) and glutamic-oxaloacetic transaminase (AST) > twice the upper limits of normal Impairment of renal function, serum creatinine: ≥ 133mmol/L for female，≥ 135mmol/L for male Serious chronic gastrointestinal diseases Edema Serious heart diseases, such as cardiac insufficiency (level III or more according to NYHA), acute coronary syndrome and old myocardial infraction Blood pressure: Systolic blood pressure (SBP) ≥ 180mmHg and/or diastolic blood pressure (DBP) ≥ 110mmHg White blood count (WBC) < 4.0×109/L or platelet count (PLT) < 90×109/L，or definite anemia (Hb：< 120g/L for male, < 110g/L for female), or other hematological diseases Endocrine system diseases, such as hyperthyroidism and hypercortisolism Experimental drug allergy or frequent hypoglycemia Psychiatric disorders, drug or other substance abuse Diabetic ketoacidosis and hyperosmolar nonketotic coma requiring insulin therapy Stressful situations such as surgery, serious trauma and so on Chronic hypoxic diseases such as pulmonary emphysema and pulmonary heart disease Combined use of drugs effecting glucose metabolism such as glucocorticoid Tumor, especially bladder tumor and/or family history of bladder tumor and/or long-term hematuria

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: glargine + exenatide<br>Type 2 diabetic patients with inadequate glycaemic control on premixed human insulin and metformin previously. After a 12-week run-in period , switching premix human insulin to glargine ( once-daily subcutaneous injection at bedtime) combination with exenatide (subcutaneous injection, twice-daily). | Drug: glargine + exenatide<br>* glargine ( once-daily subcutaneous injection at bedtime) combination with exenatide (subcutaneous injection, twice-daily)<br>|
| Active Comparator: aspart 30<br>Type 2 diabetic patients with inadequate glycaemic control on premixed human insulin and metformin previously. After a 12-week run-in period , switching premix human insulin to aspart 30 ( subcutaneous injection, twice daily). | Drug: aspart 30<br>* aspart 30 ( subcutaneous injection, twice daily)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the absolute change in HbA1c from baseline to 24-week endpoint of basal insulin glargine combination with exenatide bid vs. switching to aspart30 in type 2 diabetic patients inadequately controlled on premixed human insulin and metformin. |  | from baseline to 24-week endpoint | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c from baseline to 12 weeks endpoint |  | from baseline to 12 weeks endpoint | 
| The percentage of participants who achieved HbA1c ≤ 6.5% and < 7% |  | 12 weeks and 24 weeks | 
| Fasting blood glucose |  | 12 weeks and 24 weeks | 
| Daily insulin use |  | baseline, 12 weeks and 24 weeks | 
| Change in body weight |  | from baseline to 12 and 24 weeks | 
| The incidence and rate of hypoglycaemic events during the study |  | baseline, 12 weeks and 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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exenatide, glargine, aspart 30