To Evaluate the Effect of Liraglutide Versus Glimepiride (Amaryl®) on Haemoglobin A1c (LEAD-3)

Liraglutide Effect and Action in Diabetes (LEAD-3): Effect on Glycemic Control of Liraglutide Versus Glimepiride in Type 2 Diabetes

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).

Study Overview

• Status: Terminated
• Conditions: Diabetes Mellitus, Type 2; Diabetes
• Intervention / Treatment: Drug: liraglutide; Drug: liraglutide; Drug: placebo; Drug: placebo; Drug: placebo; Drug: glimepiride

• Study Type: Interventional
• Enrollment (Actual): 746
• Phase: Phase 3

Contacts and Locations

Study Locations

• Mexico
  • Chihuahua, Chih, Mexico, 31000
    • Novo Nordisk Investigational Site
  • Ciudad de México, D.F., Mexico, 06100
    • Novo Nordisk Investigational Site
  • Ciudad de México, D.F., Mexico, 14050
    • Novo Nordisk Investigational Site
  • Guadalajara, Mexico, 44600
    • Novo Nordisk Investigational Site
  • Hermosillo, Son., Mexico, 83000
    • Novo Nordisk Investigational Site
  • Mexico D.F., Mexico, 06700
    • Novo Nordisk Investigational Site
  • Mexico, D.F., Mexico, 01120
    • Novo Nordisk Investigational Site
  • Monterrey, N.L., Mexico, 64000
    • Novo Nordisk Investigational Site
  • Monterrey, NL, Mexico, 66260
    • Novo Nordisk Investigational Site
  • Santiago de Querétaro, Qro., Mexico, 76178
    • Novo Nordisk Investigational Site
  • Tampico, Mexico, 80109
    • Novo Nordisk Investigational Site
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44650
      • Novo Nordisk Investigational Site
  • Morelos
    • Cuernavaca, Morelos, Mexico, 62250
      • Novo Nordisk Investigational Site
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64460
      • Novo Nordisk Investigational Site
• Puerto Rico
  • Rio Piedras, Puerto Rico, 00921
    • Novo Nordisk Investigational Site
• United States
  • California
    • Concord, California, United States, 94520
      • Novo Nordisk Investigational Site
    • Escondido, California, United States, 92025
      • Novo Nordisk Investigational Site
    • Fullerton, California, United States, 92835
      • Novo Nordisk Investigational Site
    • Inglewood, California, United States, 90301
      • Novo Nordisk Investigational Site
    • Mission Viejo, California, United States, 92691
      • Novo Nordisk Investigational Site
    • Orange, California, United States, 92869
      • Novo Nordisk Investigational Site
    • Santa Barbara, California, United States, 93105
      • Novo Nordisk Investigational Site
    • Spring Valley, California, United States, 91978
      • Novo Nordisk Investigational Site
    • Vista, California, United States, 92084
      • Novo Nordisk Investigational Site
    • Walnut Creek, California, United States, 94598
      • Novo Nordisk Investigational Site
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Novo Nordisk Investigational Site
    • Delray Beach, Florida, United States, 33484
      • Novo Nordisk Investigational Site
    • Jacksonville, Florida, United States, 32216
      • Novo Nordisk Investigational Site
    • Jacksonville, Florida, United States, 32205
      • Novo Nordisk Investigational Site
    • Longwood, Florida, United States, 32779
      • Novo Nordisk Investigational Site
    • Ocala, Florida, United States, 34471
      • Novo Nordisk Investigational Site
    • St. Cloud, Florida, United States, 34769
      • Novo Nordisk Investigational Site
  • Georgia
    • Athens, Georgia, United States, 30606
      • Novo Nordisk Investigational Site
    • Atlanta, Georgia, United States, 30318
      • Novo Nordisk Investigational Site
    • Atlanta, Georgia, United States, 30339
      • Novo Nordisk Investigational Site
    • Atlanta, Georgia, United States, 30032
      • Novo Nordisk Investigational Site
    • Atlanta, Georgia, United States, 30034
      • Novo Nordisk Investigational Site
    • Blue Ridge, Georgia, United States, 30513
      • Novo Nordisk Investigational Site
    • Columbus, Georgia, United States, 31904
      • Novo Nordisk Investigational Site
    • Marietta, Georgia, United States, 30060
      • Novo Nordisk Investigational Site
    • Powder Springs, Georgia, United States, 30127
      • Novo Nordisk Investigational Site
    • Tucker, Georgia, United States, 30084
      • Novo Nordisk Investigational Site
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Novo Nordisk Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Novo Nordisk Investigational Site
    • Chicago, Illinois, United States, 60611
      • Novo Nordisk Investigational Site
    • Maywood, Illinois, United States, 60153
      • Novo Nordisk Investigational Site
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Novo Nordisk Investigational Site
  • Iowa
    • Des Moines, Iowa, United States, 50314
      • Novo Nordisk Investigational Site
  • Kansas
    • Shawnee Mission, Kansas, United States, 66204
      • Novo Nordisk Investigational Site
    • Topeka, Kansas, United States, 66606
      • Novo Nordisk Investigational Site
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Novo Nordisk Investigational Site
    • Lexington, Kentucky, United States, 40536
      • Novo Nordisk Investigational Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Novo Nordisk Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21218
      • Novo Nordisk Investigational Site
    • Hyattsville, Maryland, United States, 20782
      • Novo Nordisk Investigational Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Novo Nordisk Investigational Site
    • St. Paul, Minnesota, United States, 55108
      • Novo Nordisk Investigational Site
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Novo Nordisk Investigational Site
    • Tupelo, Mississippi, United States, 38801
      • Novo Nordisk Investigational Site
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • Novo Nordisk Investigational Site
    • St. Louis, Missouri, United States, 63110
      • Novo Nordisk Investigational Site
    • St. Louis, Missouri, United States, 63104
      • Novo Nordisk Investigational Site
    • St. Peters, Missouri, United States, 63376
      • Novo Nordisk Investigational Site
  • Montana
    • Butte, Montana, United States, 59701
      • Novo Nordisk Investigational Site
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Novo Nordisk Investigational Site
  • Nevada
    • Reno, Nevada, United States, 89502
      • Novo Nordisk Investigational Site
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Novo Nordisk Investigational Site
    • Lawrenceville, New Jersey, United States, 08648
      • Novo Nordisk Investigational Site
    • Plainsboro, New Jersey, United States, 08536
      • Novo Nordisk Investigational Site
  • New York
    • Albany, New York, United States, 12206
      • Novo Nordisk Investigational Site
    • Lewiston, New York, United States, 14092
      • Novo Nordisk Investigational Site
    • New York, New York, United States, 10023
      • Novo Nordisk Investigational Site
    • Northport, New York, United States, 11768
      • Novo Nordisk Investigational Site
    • Staten Island, New York, United States, 10301
      • Novo Nordisk Investigational Site
    • Syracuse, New York, United States, 13210
      • Novo Nordisk Investigational Site
    • West Seneca, New York, United States, 14224
      • Novo Nordisk Investigational Site
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Novo Nordisk Investigational Site
    • Charlotte, North Carolina, United States, 28277
      • Novo Nordisk Investigational Site
    • Durham, North Carolina, United States, 27710
      • Novo Nordisk Investigational Site
    • Greensboro, North Carolina, United States, 27408
      • Novo Nordisk Investigational Site
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Novo Nordisk Investigational Site
    • Dayton, Ohio, United States, 45439
      • Novo Nordisk Investigational Site
    • Mentor, Ohio, United States, 44060
      • Novo Nordisk Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Novo Nordisk Investigational Site
    • Oklahoma City, Oklahoma, United States, 73104
      • Novo Nordisk Investigational Site
    • Tulsa, Oklahoma, United States, 74104
      • Novo Nordisk Investigational Site
  • Oregon
    • Bend, Oregon, United States, 97710
      • Novo Nordisk Investigational Site
    • Eugene, Oregon, United States, 97401
      • Novo Nordisk Investigational Site
    • Medford, Oregon, United States, 97504-8491
      • Novo Nordisk Investigational Site
    • Medford, Oregon, United States, 97504
      • Novo Nordisk Investigational Site
  • Pennsylvania
    • Lancaster, Pennsylvania, United States, 17601
      • Novo Nordisk Investigational Site
    • Norristown, Pennsylvania, United States, 19401
      • Novo Nordisk Investigational Site
    • Philadelphia, Pennsylvania, United States, 19107
      • Novo Nordisk Investigational Site
  • Rhode Island
    • East Providence, Rhode Island, United States, 02914
      • Novo Nordisk Investigational Site
  • South Carolina
    • Greer, South Carolina, United States, 29651
      • Novo Nordisk Investigational Site
    • Spartanburg, South Carolina, United States, 29303
      • Novo Nordisk Investigational Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37411
      • Novo Nordisk Investigational Site
  • Texas
    • Arlington, Texas, United States, 76014
      • Novo Nordisk Investigational Site
    • Corpus Christi, Texas, United States, 78412
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75230
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75231
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75246
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75208
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75224
      • Novo Nordisk Investigational Site
    • Houston, Texas, United States, 77024
      • Novo Nordisk Investigational Site
    • Houston, Texas, United States, 77074
      • Novo Nordisk Investigational Site
    • Houston, Texas, United States, 77030
      • Novo Nordisk Investigational Site
    • Houston, Texas, United States, 77025
      • Novo Nordisk Investigational Site
    • Midland, Texas, United States, 79707
      • Novo Nordisk Investigational Site
    • San Antonio, Texas, United States, 78229
      • Novo Nordisk Investigational Site
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Novo Nordisk Investigational Site
  • Virginia
    • Richmond, Virginia, United States, 23249
      • Novo Nordisk Investigational Site
  • Washington
    • Edmonds, Washington, United States, 98026-7610
      • Novo Nordisk Investigational Site
    • Olympia, Washington, United States, 98502
      • Novo Nordisk Investigational Site
    • Renton, Washington, United States, 98057
      • Novo Nordisk Investigational Site
    • Spokane, Washington, United States, 99218
      • Novo Nordisk Investigational Site
    • Tacoma, Washington, United States, 98405
      • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Lira 1.8; 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).	Drug: liraglutide; 1.2 mg for s.c. (under the skin) injection; Drug: liraglutide; 1.8 mg for s.c. (under the skin) injection; Drug: placebo; Glimepiride placebo, 8mg capsule; Drug: placebo; Liraglutide placebo, 200 mcl; Drug: placebo; Liraglutide placebo, 300 mcl
EXPERIMENTAL: Lira 1.2; 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).	Drug: liraglutide; 1.2 mg for s.c. (under the skin) injection; Drug: liraglutide; 1.8 mg for s.c. (under the skin) injection; Drug: placebo; Glimepiride placebo, 8mg capsule; Drug: placebo; Liraglutide placebo, 200 mcl; Drug: placebo; Liraglutide placebo, 300 mcl
ACTIVE_COMPARATOR: Glimepiride - 1; 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).	Drug: placebo; Glimepiride placebo, 8mg capsule; Drug: placebo; Liraglutide placebo, 200 mcl; Drug: placebo; Liraglutide placebo, 300 mcl; Drug: glimepiride; 8 mg capsule
ACTIVE_COMPARATOR: Glimepiride - 2; 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).	Drug: placebo; Glimepiride placebo, 8mg capsule; Drug: placebo; Liraglutide placebo, 200 mcl; Drug: placebo; Liraglutide placebo, 300 mcl; Drug: glimepiride; 8 mg capsule

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Body Weight at Week 52	Change in body weight from baseline (week 0) to 52 weeks (end of double-blind period)	week 0, week 52
Change in Body Weight at Week 104	Change in body weight from baseline (week 0) to 104 weeks (end of 52-week extension)	week 0, week 104
Change in Body Weight at Week 156	Change in body weight from baseline (week 0) to 156 weeks	week 0, week 156
Change in Fasting Plasma Glucose at Week 52	Change in fasting plasma glucose (FPG) from baseline (week 0) to 52 weeks (end of double-blind period)	week 0, week 52
Change in Fasting Plasma Glucose at Week 104	Change in fasting plasma glucose (FPG) from baseline (week 0) to 104 weeks (end of 52-week extension)	week 0, week 104
Change in Fasting Plasma Glucose at Week 156	Change in fasting plasma glucose (FPG) from baseline (week 0) to 156 weeks	week 0, week 156
Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at 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.	week 0, week 52
Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at 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.	week 0, week 104
Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at 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.	week 0, week 156
Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at 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.	week 0, week 52
Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at 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.	week 0, week 104
Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at 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.	week 0, week 156
Hypoglycaemic Episodes	Total number of hypoglycaemic episodes occuring from baseline (week 0) to 104 weeks (end of the 52-week extension). 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.	weeks 0-104
Hypoglycaemic Episodes	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.	weeks 104-195

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• 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. doi: 10.1186/1475-2840-8-12.
• McGill JB. Insights from the Liraglutide Clinical Development Program--the Liraglutide Effect and Action in Diabetes (LEAD) studies. Postgrad Med. 2009 May;121(3):16-25. doi: 10.3810/pgm.2009.05.1998.
• Blonde L, Russell-Jones D. The safety and efficacy of liraglutide with or without oral antidiabetic drug therapy in type 2 diabetes: an overview of the LEAD 1-5 studies. Diabetes Obes Metab. 2009 Dec;11 Suppl 3:26-34. doi: 10.1111/j.1463-1326.2009.01075.x.
• Jendle J, Nauck MA, Matthews DR, Frid A, Hermansen K, During M, Zdravkovic M, Strauss BJ, Garber AJ; LEAD-2 and LEAD-3 Study Groups. Weight loss with liraglutide, a once-daily human glucagon-like peptide-1 analogue for type 2 diabetes treatment as monotherapy or added to metformin, is primarily as a result of a reduction in fat tissue. Diabetes Obes Metab. 2009 Dec;11(12):1163-72. doi: 10.1111/j.1463-1326.2009.01158.x.
• Buse JB, Garber A, Rosenstock J, Schmidt WE, Brett JH, Videbaek N, Holst J, Nauck M. Liraglutide treatment is associated with a low frequency and magnitude of antibody formation with no apparent impact on glycemic response or increased frequency of adverse events: results from the Liraglutide Effect and Action in Diabetes (LEAD) trials. J Clin Endocrinol Metab. 2011 Jun;96(6):1695-702. doi: 10.1210/jc.2010-2822. Epub 2011 Mar 30.
• Bode BW, Brett J, Falahati A, Pratley RE. Comparison of the efficacy and tolerability profile of liraglutide, a once-daily human GLP-1 analog, in patients with type 2 diabetes >/=65 and <65 years of age: a pooled analysis from phase III studies. Am J Geriatr Pharmacother. 2011 Dec;9(6):423-33. doi: 10.1016/j.amjopharm.2011.09.007. Epub 2011 Nov 4.
• Henry RR, Buse JB, Sesti G, Davies MJ, Jensen KH, Brett J, Pratley RE. Efficacy of antihyperglycemic therapies and the influence of baseline hemoglobin A(1C): a meta-analysis of the liraglutide development program. Endocr Pract. 2011 Nov-Dec;17(6):906-13. doi: 10.4158/ep.17.6.906.
• Zinman B, Schmidt WE, Moses A, Lund N, Gough S. Achieving a clinically relevant composite outcome of an HbA1c of <7% without weight gain or hypoglycaemia in type 2 diabetes: a meta-analysis of the liraglutide clinical trial programme. Diabetes Obes Metab. 2012 Jan;14(1):77-82. doi: 10.1111/j.1463-1326.2011.01493.x. Epub 2011 Oct 30.
• Niswender K, Pi-Sunyer X, Buse J, Jensen KH, Toft AD, Russell-Jones D, Zinman B. Weight change with liraglutide and comparator therapies: an analysis of seven phase 3 trials from the liraglutide diabetes development programme. Diabetes Obes Metab. 2013 Jan;15(1):42-54. doi: 10.1111/j.1463-1326.2012.01673.x. Epub 2012 Sep 9.
• Alves C, Batel-Marques F, Macedo AF. A meta-analysis of serious adverse events reported with exenatide and liraglutide: acute pancreatitis and cancer. Diabetes Res Clin Pract. 2012 Nov;98(2):271-84. doi: 10.1016/j.diabres.2012.09.008. Epub 2012 Sep 23.
• King AB, Montanya E, Pratley RE, Blonde L, Svendsen CB, Donsmark M, Sesti G. Liraglutide achieves A1C targets more often than sitagliptin or exenatide when added to metformin in patients with type 2 diabetes and a baseline A1C <8.0%. Endocr Pract. 2013 Jan-Feb;19(1):64-72. doi: 10.4158/EP12232.OR.
• Jensen TM, Saha K, Steinberg WM. Is there a link between liraglutide and pancreatitis? A post hoc review of pooled and patient-level data from completed liraglutide type 2 diabetes clinical trials. Diabetes Care. 2015 Jun;38(6):1058-66. doi: 10.2337/dc13-1210. Epub 2014 Dec 12. Erratum In: Diabetes Care. 2015 Aug;38(8):1622.
• Fonseca VA, Devries JH, Henry RR, Donsmark M, Thomsen HF, Plutzky J. Reductions in systolic blood pressure with liraglutide in patients with type 2 diabetes: insights from a patient-level pooled analysis of six randomized clinical trials. J Diabetes Complications. 2014 May-Jun;28(3):399-405. doi: 10.1016/j.jdiacomp.2014.01.009. Epub 2014 Jan 21.
• Hegedus 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. doi: 10.1210/jc.2010-2318. Epub 2011 Jan 5.
• Garber A, Henry R, Ratner R, Garcia-Hernandez PA, Rodriguez-Pattzi H, Olvera-Alvarez I, Hale PM, Zdravkovic M, Bode B; LEAD-3 (Mono) Study Group. Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet. 2009 Feb 7;373(9662):473-81. doi: 10.1016/S0140-6736(08)61246-5. Epub 2008 Sep 24.
• Bode BW, Testa MA, Magwire M, Hale PM, Hammer M, Blonde L, Garber A; LEAD-3 Study Group. Patient-reported outcomes following treatment with the human GLP-1 analogue liraglutide or glimepiride in monotherapy: results from a randomized controlled trial in patients with type 2 diabetes. Diabetes Obes Metab. 2010 Jul;12(7):604-12. doi: 10.1111/j.1463-1326.2010.01196.x.
• Ingwersen SH, Khurana M, Madabushi R, Watson E, Jonker DM, Le Thi TD, Jacobsen LV, Tornoe CW. Dosing rationale for liraglutide in type 2 diabetes mellitus: a pharmacometric assessment. J Clin Pharmacol. 2012 Dec;52(12):1815-23. doi: 10.1177/0091270011430504. Epub 2011 Dec 15.
• Gilbert MP, Marre M, Holst JJ, Garber A, Baeres FM, Thomsen H, Pratley RE. COMPARISON OF THE LONG-TERM EFFECTS OF LIRAGLUTIDE AND GLIMEPIRIDE MONOTHERAPY ON BONE MINERAL DENSITY IN PATIENTS WITH TYPE 2 DIABETES. Endocr Pract. 2016 Apr;22(4):406-11. doi: 10.4158/EP15758.OR. Epub 2015 Nov 17.
• Davidson JA, Orsted DD, Campos C. Efficacy and safety of liraglutide, a once-daily human glucagon-like peptide-1 analogue, in Latino/Hispanic patients with type 2 diabetes: post hoc analysis of data from four phase III trials. Diabetes Obes Metab. 2016 Jul;18(7):725-8. doi: 10.1111/dom.12653. Epub 2016 Apr 28.

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start: February 1, 2006
• Primary Completion (ACTUAL): November 1, 2008
• Study Completion (ACTUAL): November 1, 2008

Study Registration Dates

• First Submitted: February 20, 2006
• First Submitted That Met QC Criteria: February 20, 2006
• First Posted (ESTIMATE): February 22, 2006

Study Record Updates

• Last Update Posted (ACTUAL): March 7, 2017
• Last Update Submitted That Met QC Criteria: January 24, 2017
• Last Verified: January 1, 2017

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Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Anti-Arrhythmia Agents; Immunosuppressive Agents; Immunologic Factors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Liraglutide; Glimepiride
• Other Study ID Numbers: NN2211-1573