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 - Full Text View

Sponsor:	Novo Nordisk
Information provided by:	Novo Nordisk
ClinicalTrials.gov Identifier:	NCT00318461

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 Mellitus, Type 2	Drug: liraglutide Drug: metformin Drug: glimepiride Drug: placebo	Phase III

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:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Diabetes Diabetes Type 2

Drug Information available for: Glimepiride Liraglutide Metformin Metformin hydrochloride

U.S. FDA Resources

Further study details as provided by Novo Nordisk:

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. Other Name: NN2211 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 Other Name: NN2211
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 Other Name: NN2211
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 Other Name: NN2211
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 Other Name: NN2211

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

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

Show 21 Study Locations

Sponsors and Collaborators

Novo Nordisk

Investigators

Study Director:

Martin Lange

Novo Nordisk

More Information

Additional Information:

Clinical Trials at Novo Nordisk This link exits the ClinicalTrials.gov site

No publications provided by Novo Nordisk

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

Hegedüs L, Moses AC, Zdravkovic M, Le Thi T, Daniels GH. GLP-1 and calcitonin concentration in humans: lack of evidence of calcitonin release from sequential screening in over 5000 subjects with type 2 diabetes or nondiabetic obese subjects treated with the human GLP-1 analog, liraglutide. J Clin Endocrinol Metab. 2011 Mar;96(3):853-60. Epub 2011 Jan 5.

Nauck M, Marre M. Adding liraglutide to oral antidiabetic drug monotherapy: efficacy and weight benefits. Postgrad Med. 2009 May;121(3):5-15.

Sullivan SD, Alfonso-Cristancho R, Conner C, Hammer M, Blonde L. Long-term outcomes in patients with type 2 diabetes receiving glimepiride combined with liraglutide or rosiglitazone. Cardiovasc Diabetol. 2009 Feb 26;8:12.

Nauck M, Frid A, Hermansen K, Shah NS, Tankova T, Mitha IH, Zdravkovic M, Düring M, Matthews DR; LEAD-2 Study Group. Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study. Diabetes Care. 2009 Jan;32(1):84-90. Epub 2008 Oct 17.

Responsible Party:	Public Access to Clinical Trials, Novo Nordisk A/S
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:	April 16, 2010
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
Metformin
Glucagon-Like Peptide 1
Hypoglycemic Agents
Physiological Effects of Drugs

Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on February 12, 2012