To Compare the Effect of Liraglutide When Given Together With Metformin With the Effect of Metformin Given Alone and With the Effect of Glimepiride and Metformin Given Together

Overview[ - collapse ][ - ]

Purpose This trial is conducted in Europe, Oceania, Africa, Asia and South America. This trial is designed to show the effect of treatment with liraglutide when adding to existing metformin therapy and to compare it with the effects of metformin monotherapy and combination therapy of metformin and glimepiride. Two trial periods: A 6 month (26 weeks) randomised, double-blinded period followed by an 18 months open-label extension, in total 2 years (104 weeks).
ConditionDiabetes
Diabetes Mellitus, Type 2
InterventionDrug: liraglutide
Drug: metformin
Drug: glimepiride
Drug: placebo
Drug: placebo
Drug: liraglutide
Drug: liraglutide
PhasePhase 3
SponsorNovo Nordisk A/S
Responsible PartyNovo Nordisk A/S
ClinicalTrials.gov IdentifierNCT00318461
First ReceivedApril 25, 2006
Last UpdatedNovember 25, 2013
Last verifiedNovember 2013

Tracking Information[ + expand ][ + ]

First Received DateApril 25, 2006
Last Updated DateNovember 25, 2013
Start DateMay 2006
Estimated Primary Completion DateNovember 2008
Current Primary Outcome Measures
  • Change in Glycosylated A1c (HbA1c) at Week 26 [Time Frame: week 0, week 26] [Designated as safety issue: No]Percentage point change in Glycosylated A1c (HbA1c) from baseline (week 0) to 26 weeks (end of randomisation)
  • Change in Glycosylated A1c (HbA1c) at Week 104 [Time Frame: week 0, week 104] [Designated as safety issue: No]Change in glycosylated A1c (HbA1c) baseline (week 0) to 104 weeks (end of randomisation)
Current Secondary Outcome Measures
  • Change in Body Weight at Week 26 [Time Frame: week 0, week 26] [Designated as safety issue: No]Change in body weight from baseline (week 0) to 26 weeks (end of randomisation)
  • Change in Body Weight at Week 104 [Time Frame: week 0, week 104] [Designated as safety issue: No]Change in body weight from baseline (week 0) to 104 weeks (end of treatment)
  • Change in Fasting Plasma Glucose (FPG) at Week 26 [Time Frame: week 0, week 26] [Designated as safety issue: No]Change in fasting plasma glucose (FPG) from baseline (week 0) to 26 weeks (end of randomisation)
  • Change in Fasting Plasma Glucose (FPG) at Week 104 [Time Frame: week 0, week 104] [Designated as safety issue: No]Change in Fasting plasma glucose (FPG) from baseline (week 0) to 104 weeks (end of treatment)
  • Change in Mean Prandial Increments of Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 26 [Time Frame: week 0, week 26] [Designated as safety issue: No]Change in mean prandial increments of plasma glucose based on self-measured 7-point plasma glucose profiles from baseline (week 0) to 26 weeks (end of randomisation). The 7 time points for self-measurements were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner) and at bedtime.
    Mean prandial increments of plasma glucose were calculated as the sum of the plasma glucose differences between values measured before and after a meal (breakfast, lunch and dinner) divided by three.
  • Change in Mean Prandial Increments of Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 104 [Time Frame: week 0, week 104] [Designated as safety issue: No]Change in mean prandial increments of plasma glucose based on self-measured 7-point plasma glucose profiles from baseline (week 0) to 104 weeks (end of treatment). The 7 time points for self-measurements were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner) and at bedtime.
    Mean prandial increments of plasma glucose were calculated as the sum of the plasma glucose differences between values measured before and after a meal (breakfast, lunch and dinner) divided by three.
  • Change in Mean Post Prandial Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 26 [Time Frame: week 0, week 26] [Designated as safety issue: No]Change in mean post prandial plasma glucose from baseline (Week 0) to 26 weeks (end of randomisation). The 7 time points for self-measurements were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner) and at bedtime. Mean post prandial plasma glucose were calculated as the sum of the post pradial plasma glucose values divided by three.
  • Change in Mean Post Prandial Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 104 [Time Frame: week 0, week 104] [Designated as safety issue: No]Change in mean post prandial plasma glucose from baseline (Week 0) to 104 weeks (end of treatment) The 7 time points for self-measurements were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner) and at bedtime. Mean post prandial plasma glucose were calculated as the sum of the post pradial plasma glucose values divided by three.
  • Change in Beta-cell Function at Week 26 [Time Frame: week 0, week 26] [Designated as safety issue: No]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).
  • Change in Beta-cell Function at Week 104 [Time Frame: week 0, week 104] [Designated as safety issue: No]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).
  • Hypoglycaemic Episodes at Week 26 [Time Frame: weeks 0-26] [Designated as safety issue: Yes]Total number of hypoglycaemic episodes occuring after baseline (week 0) until week 26 (end of randomisation). 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.
  • Hypoglycaemic Episodes at Week 104 [Time Frame: weeks 0-104] [Designated as safety issue: Yes]Total number of hypoglycaemic episodes occuring after baseline (week 0) until 104 weeks (end of treatment). 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.

Descriptive Information[ + expand ][ + ]

Brief TitleTo Compare the Effect of Liraglutide When Given Together With Metformin With the Effect of Metformin Given Alone and With the Effect of Glimepiride and Metformin Given Together
Official TitleLiraglutide Effect and Action in Diabetes (LEAD-2): Effect on Glycaemic Control After Once Daily Administration of Liraglutide in Combination With Metformin Versus Metformin Monotherapy Versus Metformin and Glimepiride Combination Therapy in Subjects With Type 2 Diabetes
Brief Summary
This trial is conducted in Europe, Oceania, Africa, Asia and South America. This trial is
designed to show the effect of treatment with liraglutide when adding to existing metformin
therapy and to compare it with the effects of metformin monotherapy and combination therapy
of metformin and glimepiride. Two trial periods: A 6 month (26 weeks) randomised,
double-blinded period followed by an 18 months open-label extension, in total 2 years (104
weeks).
Detailed DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 3
Study DesignAllocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Condition
  • Diabetes
  • Diabetes Mellitus, Type 2
InterventionDrug: liraglutide
0.6 mg for s.c. (under the skin) injection.
Drug: metformin
1.5-2.0 g tablets
Drug: glimepiride
4 mg tablets
Drug: placebo
Glimepiride placebo 1 mg and 2 mg tablets
Drug: placebo
Liraglutide placebo 1-3 mL for s.c. (under the skin) injection
Drug: liraglutide
1.2 mg for s.c. (under the skin) injection
Drug: liraglutide
1.8 mg for s.c. (under the skin) injection
Study Arm (s)
  • Experimental: Lira 0.6 + Met
    Liraglutide 0.6 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day
  • Experimental: Lira 1.2 + Met
    Liraglutide 1.2 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day
  • Experimental: Lira 1.8 + Met
    Liraglutide 1.8 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day
  • Active Comparator: Met Mono
    Metformin 1.5-2.0 g/day + liraglutide placebo + glimepiride placebo
  • Active Comparator: Met + Glim
    Glimepiride 4 mg/day + metformin 1.5-2.0 g/day + liraglutide placebo

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment1091
Estimated Completion DateNovember 2008
Estimated Primary Completion DateMay 2007
Eligibility Criteria
Inclusion Criteria:

- Subjects diagnosed with type 2 diabetes and treated with oral anti-diabetic drugs
(OADs) for at least 3 months

- HbA1c: 7.0-11.0 % (both incl.) in subjects on OAD monotherapy. 7.0-10.0 % (both
incl.) in subjects on OAD combination therapy

- Body Mass Index (BMI) less than or equal 40 kg/m2

Exclusion Criteria:

- Subjects treated with insulin within the last three months

- Subjects with any serious medical condition

- Females of child bearing potential who are pregnant, breast-feeding or have the
intention of becoming pregnant or not using adequate contraceptive methods

- Subjects using any drug (except for OADs), which in the Investigator's opinion could
interfere with the glucose level (e.g. systemic corticosteroids)
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesArgentina, Australia, Belgium, Bulgaria, Croatia, Denmark, Germany, Hungary, India, Ireland, Italy, Netherlands, New Zealand, Norway, Romania, Russian Federation, Slovakia, South Africa, Spain, Sweden, United Kingdom

Administrative Information[ + expand ][ + ]

NCT Number NCT00318461
Other Study ID NumbersNN2211-1572
Has Data Monitoring CommitteeNo
Information Provided ByNovo Nordisk A/S
Study SponsorNovo Nordisk A/S
CollaboratorsNot Provided
Investigators Study Director: Martin Lange Novo Nordisk A/S
Verification DateNovember 2013

Locations[ + expand ][ + ]

Argentina
Ciudad Autonoma de Bs As, Argentina, C1405CWB
Australia
Box Hill, Australia, 3128
Belgium
Gent, Belgium, 9000
Bulgaria
Sofia, Bulgaria, 1431
Croatia
Zagreb, Croatia, 10 000
Denmark
Herlev, Denmark, 2730
Germany
Bad Lauterberg, Germany, 37431
Hungary
Pecs, Hungary, 7631
India
Bangalore, India, 560034
Ireland
Dublin, Ireland, DUBLIN 7
Italy
Milano, Italy, 20132
Netherlands
Groningen, Netherlands, 9728 NT
New Zealand
Auckland, New Zealand
Norway
Hamar, Norway, 2317
Romania
Constanta, Romania, 900591
Russian Federation
Moscow, Russian Federation, 123448
Slovakia
Kosice, Slovakia, 04-001
South Africa, Gauteng
Johannesburg, Gauteng, South Africa, 27 11
Spain
Málaga, Spain, 29010
Sweden
Stockholm, Sweden, 171 76
United Kingdom
East Horsley, United Kingdom, KT24 6QT