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)

This study has been completed.
Sponsor:
Information provided by:
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT00318461
First received: April 25, 2006
Last updated: November 25, 2013
Last verified: November 2013
  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).


Condition Intervention Phase
Diabetes
Diabetes Mellitus, Type 2
Drug: liraglutide
Drug: metformin
Drug: glimepiride
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by Novo Nordisk A/S:

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)


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.


Enrollment: 1091
Study Start Date: May 2006
Study Completion Date: November 2008
Primary Completion Date: May 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00318461

  Show 21 Study Locations
Sponsors and Collaborators
Novo Nordisk A/S
Investigators
Study Director: Martin Lange Novo Nordisk A/S
  More Information

Additional Information:
No publications provided by Novo Nordisk A/S

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00318461     History of Changes
Other Study ID Numbers: NN2211-1572
Study First Received: April 25, 2006
Results First Received: February 23, 2010
Last Updated: November 25, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Spain: Spanish Agency of Medicines
Croatia: Ministry of Health and Social Care
Russia: Pharmacological Committee, Ministry of Health
Denmark: Danish Medicines Agency
Romania: State Institute for Drug Control
Hungary: National Institute of Pharmacy
Bulgaria: Bulgarian Drug Agency
South Africa: Medicines Control Council
Netherlands: Dutch Health Care Inspectorate
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Ireland: Irish Medicines Board
Australia: Department of Health and Ageing Therapeutic Goods Administration
Norway: Norwegian Medicines Agency
Sweden: Medical Products Agency
India: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Glimepiride
Liraglutide
Metformin
Glucagon-Like Peptide 1
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on August 21, 2014