We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Try the New Site
We're building a modernized ClinicalTrials.gov! Visit Beta.ClinicalTrials.gov to try the new functionality.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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 (LEAD-2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00318461
Recruitment Status : Completed
First Posted : April 26, 2006
Results First Posted : March 12, 2010
Last Update Posted : March 7, 2017
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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).

Condition or disease Intervention/treatment Phase
Diabetes Diabetes Mellitus, Type 2 Drug: liraglutide Drug: metformin Drug: glimepiride Drug: placebo Phase 3

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1091 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Liraglutide 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
Study Start Date : May 2006
Actual Primary Completion Date : May 2007
Actual Study Completion Date : November 2008

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Lira 0.6 + Met
Liraglutide 0.6 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day
 Drug: liraglutide
0.6 mg for s.c. (under the skin) injection.

Drug: metformin
1.5-2.0 g tablets

Drug: placebo
Glimepiride placebo 1 mg and 2 mg tablets
Experimental: Lira 1.2 + Met
Liraglutide 1.2 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day
 Drug: metformin
1.5-2.0 g tablets

Drug: placebo
Glimepiride placebo 1 mg and 2 mg tablets

Drug: liraglutide
1.2 mg for s.c. (under the skin) injection
Experimental: Lira 1.8 + Met
Liraglutide 1.8 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day
 Drug: metformin
1.5-2.0 g tablets

Drug: placebo
Glimepiride placebo 1 mg and 2 mg tablets

Drug: liraglutide
1.8 mg for s.c. (under the skin) injection
Active Comparator: Met Mono
Metformin 1.5-2.0 g/day + liraglutide placebo + glimepiride placebo
 Drug: metformin
1.5-2.0 g 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
Active Comparator: Met + Glim
Glimepiride 4 mg/day + metformin 1.5-2.0 g/day + liraglutide placebo
 Drug: metformin
1.5-2.0 g tablets

Drug: glimepiride
4 mg tablets

Drug: placebo
Liraglutide placebo 1-3 mL for s.c. (under the skin) injection


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Change in Glycosylated A1c (HbA1c) at Week 26 [ Time Frame: week 0, week 26 ]
    Percentage point change in Glycosylated A1c (HbA1c) from baseline (week 0) to 26 weeks (end of randomisation)

  2. Change in Glycosylated A1c (HbA1c) at Week 104 [ Time Frame: week 0, week 104 ]
    Change in glycosylated A1c (HbA1c) baseline (week 0) to 104 weeks (end of randomisation)


Secondary Outcome Measures :
  1. Change in Body Weight at Week 26 [ Time Frame: week 0, week 26 ]
    Change in body weight from baseline (week 0) to 26 weeks (end of randomisation)

  2. Change in Body Weight at Week 104 [ Time Frame: week 0, week 104 ]
    Change in body weight from baseline (week 0) to 104 weeks (end of treatment)

  3. Change in Fasting Plasma Glucose (FPG) at Week 26 [ Time Frame: week 0, week 26 ]
    Change in fasting plasma glucose (FPG) from baseline (week 0) to 26 weeks (end of randomisation)

  4. Change in Fasting Plasma Glucose (FPG) at Week 104 [ Time Frame: week 0, week 104 ]
    Change in Fasting plasma glucose (FPG) from baseline (week 0) to 104 weeks (end of treatment)

  5. 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 ]

    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.


  6. 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 ]

    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.


  7. 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 ]
    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.

  8. 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 ]
    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.

  9. Change in Beta-cell Function at Week 26 [ Time Frame: week 0, week 26 ]

    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).


  10. Change in Beta-cell Function at Week 104 [ Time Frame: week 0, week 104 ]

    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).


  11. Hypoglycaemic Episodes at Week 26 [ Time Frame: weeks 0-26 ]
    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.

  12. Hypoglycaemic Episodes at Week 104 [ Time Frame: weeks 0-104 ]
    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.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00318461


Locations
Show Show 190 study locations
Sponsors and Collaborators
Novo Nordisk A/S
Investigators
Layout table for investigator information
Study Director: Global Clinical Registry (GCR, 1452) Novo Nordisk A/S
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Additional Information:

Publications of Results:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT00318461    
Other Study ID Numbers: NN2211-1572
First Posted: April 26, 2006    Key Record Dates
Results First Posted: March 12, 2010
Last Update Posted: March 7, 2017
Last Verified: January 2017
Additional relevant MeSH terms:
Layout table for MeSH terms
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Metformin
Liraglutide
Glimepiride
 Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Anti-Arrhythmia Agents
Immunosuppressive Agents
Immunologic Factors