To Evaluate the Effect of Liraglutide Versus Glimepiride (Amaryl®) on Haemoglobin A1c

Phase 3

Terminated

Conditions: Diabetes
Diabetes Mellitus, Type 2

Interventions: Drug: liraglutide
Drug: glimepiride
Drug: placebo

Registration Number: NCT00294723

Lead Sponsor: Novo Nordisk A/S

Brief Summary: This trial is conducted in North America (the United States of America (USA) and Mexico).

The trial is designed to evaluate the effects of treatment with liraglutide versus glimepiride in subjects with type 2 diabetes. The trial is a 52-week randomised, double-blind trial period plus a 52-week open-label extension (week 104) followed by an additional 156-week continued open-label extension. The total duration of the treatment period is planned to be 260 weeks (5 years).

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 746

Inclusion Criteria

Type 2 diabetes
TTreatment with diet/exercise or with not more than half maximal dose of oral anti-diabetic drugs alone for at least 2 months
Diet/exercise treated subjects with HbA1c between 7.0% and 11%, inclusive
OAD (oral anti-diabetic drug) treated subjects with HbA1c between 7.0% and 10%, inclusive
Body Mass Index (BMI) less than or equal to 45 kg/m^2

Exclusion Criteria

Treatment with insulin for the last 3 months, except short-term treatment for intercurrent illness
Treatment with any drug that could interfere with the glucose level (besides use of a single anti-diabetic compound)
Any serious medical condition

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lira 1.8	liraglutide	Liraglutide 1.8 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.8 mg once daily in the extension periods (weeks 52-195).
Lira 1.8	placebo	Liraglutide 1.8 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.8 mg once daily in the extension periods (weeks 52-195).
Lira 1.2	liraglutide	Liraglutide 1.2 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.2 mg once daily in the extension periods (weeks 52-195).
Lira 1.2	placebo	Liraglutide 1.2 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.2 mg once daily in the extension periods (weeks 52-195).
Glimepiride - 1	glimepiride	Glimepiride 8 mg once daily + liraglutide placebo 200 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension periods (weeks 52-195).
Glimepiride - 1	placebo	Glimepiride 8 mg once daily + liraglutide placebo 200 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension periods (weeks 52-195).
Glimepiride - 2	glimepiride	Glimepiride 8 mg once daily + liraglutide placebo 300 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension periods (weeks 52-195).
Glimepiride - 2	placebo	Glimepiride 8 mg once daily + liraglutide placebo 300 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension periods (weeks 52-195).

Primary Outcome Measures

Name	Time	Method
Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 52	week 0, week 52	Percentage point change in Glycosylated Haemoglobin A1c (HbA1c) from baseline (week 0) to 52 weeks (end of double-blind period)
Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 104	week 0, week 104	Percentage point change in Glycosylated Haemoglobin A1c (HbA1c) from baseline (week 0) to 104 weeks (end of 52-week extension)
Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 156	week 0, week 156	Percentage point change in Glycosylated Haemoglobin A1c (HbA1c) from baseline (week 0) to 156 weeks

Secondary Outcome Measures

Name	Time	Method
Change in Body Weight at Week 52	week 0, week 52	Change in body weight from baseline (week 0) to 52 weeks (end of double-blind period)
Change in Body Weight at Week 104	week 0, week 104	Change in body weight from baseline (week 0) to 104 weeks (end of 52-week extension)
Change in Body Weight at Week 156	week 0, week 156	Change in body weight from baseline (week 0) to 156 weeks
Change in Fasting Plasma Glucose at Week 52	week 0, week 52	Change in fasting plasma glucose (FPG) from baseline (week 0) to 52 weeks (end of double-blind period)
Change in Fasting Plasma Glucose at Week 104	week 0, week 104	Change in fasting plasma glucose (FPG) from baseline (week 0) to 104 weeks (end of 52-week extension)
Change in Fasting Plasma Glucose at Week 156	week 0, week 156	Change in fasting plasma glucose (FPG) from baseline (week 0) to 156 weeks
Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 52	week 0, week 52	Change in mean postprandial glucose (PPG) based on self-measured 8-point plasma glucose profiles from baseline (week 0) to 52 weeks (end of double-blind period). The 8 time points for self-measurements of plasma glucose were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min.
Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 104	week 0, week 104	Change in mean postprandial glucose (PPG) based on self-measured 8-point plasma glucose profiles from baseline (week 0) to 104 weeks (end of 52-week extension). The 8 time points for self-measurements of plasma glucose were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min.
Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 156	week 0, week 156	Change in mean postprandial glucose (PPG) based on self-measured 8-point plasma glucose profiles from baseline (week 0) to 156 weeks. The 8 time points for self-measurements of plasma glucose were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min.
Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 52	week 0, week 52	Change in mean prandial increments of plasma glucose from baseline (week 0) to 52 weeks (end of double-blind period). The 8 time points for self-measured 8-point plasma glucose profiles were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min. Mean prandial increments of plasma glucose were calculated as the sum of the plasma glucose differences between post- and pre-meal values (for breakfast, lunch and dinner) divided by three.
Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 104	week 0, week 104	Change in mean prandial increments of plasma glucose from baseline (week 0) to 104 weeks (end of 52-week extension). The 8 time points for self-measured 8-point plasma glucose profiles were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min. Mean prandial increments of plasma glucose were calculated as the sum of the plasma glucose differences between post- and pre-meal values (for breakfast, lunch and dinner) divided by three.
Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 156	week 0, week 156	Change in mean prandial increments (incr.) of plasma glucose from baseline (week 0) to 156 weeks. The 8 time points for self-measured 8-point plasma glucose profiles were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min. Mean prandial increments of plasma glucose were calculated as the sum of the plasma glucose differences between post- and pre-meal values (for breakfast, lunch and dinner) divided by three.
Hypoglycaemic Episodes	weeks 104-195	Total number of hypoglycaemic episodes occuring from week 104 to end of trial (week 195). 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 56 mg/dL. Symptoms only if subject was able to treat her/himself and with no plasma glucose measurement or plasma glucose higher than or equal to 56 mg/dL.