Effect of Liraglutide or Glimepiride Added to Metformin on Blood Glucose Control in Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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This trial is conducted in Asia. The trial is designed to compare the effect on glycaemic control of liraglutide or glimepiride added to metformin in subjects with type 2 diabetes

Official Title
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Effect of Liraglutide or Glimepiride Added to Metformin on Glycaemic Control in Subjects With Type 2 Diabetes

Conditions
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Diabetes, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: liraglutide
* Drug: placebo
* Drug: liraglutide
* Drug: liraglutide
* Drug: glimepiride
* Drug: metformin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes Subjects diagnosed with type 2 diabetes and treated with one or more oral antidiabetic drugs (OADs) for the last 3 months HbA1c: 7.0-11.0% (both incl.) for subjects on OAD alone HbA1c: 7.0-10.0 % (both incl.) for subjects on OAD combination therapy BMI less than 45.0 kg/m^2 Exclusion Criteria: Treatment with insulin within the last 3 months prior to the trial Impaired liver or/and renal function Significant cardiovascular disease over the last 6 months Known retinopathy or maculopathy Recurrent major hypoglycaemia or hypoglycaemic unawareness

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lira 0.6 + Met<br>Liraglutide 0.6 mg + metformin + glimepiride placebo | Drug: liraglutide<br>* 0.6 mg/day, s.c. (under the skin) injection<br>Drug: placebo<br>* Glimepiride placebo, capsules<br>Drug: metformin<br>* Tablets, 1.5-2.0 g/day<br>|
| Experimental: Lira 1.2 + Met<br>Liraglutide 1.2 mg + metformin + glimepiride placebo | Drug: placebo<br>* Glimepiride placebo, capsules<br>Drug: liraglutide<br>* 1.2 mg/day, s.c. (under the skin) injection<br>Drug: metformin<br>* Tablets, 1.5-2.0 g/day<br>|
| Experimental: Lira 1.8 + Met<br>Liraglutide + metformin + glimepiride placebo | Drug: placebo<br>* Glimepiride placebo, capsules<br>Drug: liraglutide<br>* 1.8 mg/day, s.c. (under the skin) injection<br>Drug: metformin<br>* Tablets, 1.5-2.0 g/day<br>|
| Experimental: Glim + Met<br>Glimepiride 4.0 mg + metformin + liraglutide placebo | Drug: glimepiride<br>* Capsules, 4.0 mg/day<br>Drug: metformin<br>* Tablets, 1.5-2.0 g/day<br>Drug: placebo<br>* Liraglutide placebo, s.c. (under the skin) injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Glycosylated Haemoglobin A1c (HbA1c) | Percentage point change in Glycosylated Haemoglobin A1c (HbA1c) from baseline (week 0) to 16 weeks (end of treatment). | week 0, week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Body Weight | Change in body weight from baseline (week 0) to 16 weeks (end of treatment) | week 0, week 16 | 
| Change in Self-measured Fasting Plasma Glucose | Change in self-measured fasting plasma glucose from baseline (week 0) to 16 weeks (end of treatment). Self-measurement of plasma glucose was performed using a glucose meter and subjects were instructed to record self-measured plasma glucose values into a diary. | week 0, week 16 | 
| 7-point Self-measured Plasma Glucose Profiles | Summary of 7-Point Profiles of Self-Measured Plasma Glucose by Treatment, Week and Time. The 7 time points for self-measurements for all treatment groups were: Before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner) and at bedtime, measured over 16 weeks of treatment (at week 0, 8, 12 and 16). | week 0, 8, 12 and 16 | 
| Change in Beta-cell Function | Change in beta cell function from baseline (week 0) to 16 weeks (end of treatment). Beta-cell function was derived from fasting plasma glucose (FPG) and fasting insulin concentrations using the homeostasic model assessment (HOMA) method which uses the assumption that normal-weight normal subjects aged under 35 years have a 100% beta-cell function (HOMA-B). Beta-cell function: HOMA-B (%) = 20∙fasting insulin[uU/mL] divided by (FPG mmol/L]-3.5). | week 0, week 16 | 
| Change in Fasting Lipid Profile | Change in fasting lipid profiles from baseline (week 0) to 16 weeks (end of treatment). Fasting lipid profiles is based on: Total Cholesterol (TC) Low-density Lipoprotein-cholesterol (LDL-C) Very Low-density Lipoprotein-cholesterol (VLDL-C) High-density Lipoprotein-cholesterol (HDL-C) Triglyceride (TG) Free Fatty Acid (FFA) | week 0, week 16 | 
| Change in Fasting Lipid Profile, APO-B | Change in fasting lipid profiles based on apolipoprotein B (Apo-B) from baseline (week 0) to 16 weeks (end of treatment). | week 0, week 16 | 
| Hypoglycaemic Episodes | Total number of hypoglycaemic episodes over 16 weeks of treatment occurring from baseline (week 0) to end of treatment (week 16). Hypoglycaemic episodes were defined as major, minor, or symptoms only. Major if the subject was unable to treat her/himself. Minor if subject was able to treat her/himself and plasma glucose was below 3.1 mmol/L. Symptoms only if subject was able to treat her/himself and with no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L. | weeks 0-16 |