DiabetesPhase 3LEAD-3NCT00294723

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

A Phase 3 study testing liraglutide and glimepiride in people with Diabetes and Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 117 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

Trial summary

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. Read more about this study

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Diabetes, Diabetes Mellitus, Type 2
What is being tested?: liraglutide and glimepiride
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 746 participants
Where: 117 sitesin 3 countries
Study dates: Feb 2006to Nov 2008
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

117 sites in 3 countries.

Country

City, postcode or hospital

117 sites in 3 countries

United States102 sites

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

Other trials in United States

Mexico14 sites

Novo Nordisk Investigational Site
Chihuahua, Chih, 31000
Novo Nordisk Investigational Site
Ciudad de México, D.F., 06100
Novo Nordisk Investigational Site
Ciudad de México, D.F., 14050
Novo Nordisk Investigational Site
Cuernavaca, Morelos, 62250
Novo Nordisk Investigational Site
Guadalajara, Jalisco, 44650
Novo Nordisk Investigational Site
Guadalajara, 44600
Novo Nordisk Investigational Site
Hermosillo, Son., 83000
Novo Nordisk Investigational Site
Mexico City, 01120
Novo Nordisk Investigational Site
Mexico City, 06700
Novo Nordisk Investigational Site
Monterrey, Nuevo León, 64460
Novo Nordisk Investigational Site
Monterrey, N.L., 64000
Novo Nordisk Investigational Site
Monterrey, NL, 66260
Novo Nordisk Investigational Site
Santiago de Querétaro, Qro., 76178
Novo Nordisk Investigational Site
Tampico, 80109

Other trials in Mexico

Puerto Rico1 site

Novo Nordisk Investigational Site
Rio Piedras, 00921

Other trials in Puerto Rico

About this study

Official title: 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).

Conditions: Diabetes, Diabetes Mellitus, Type 2
Being tested: liraglutide, glimepiride, placebo
Medical subject headings: Diabetes Mellitus, Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

liraglutideDrug
1.8 mg for s.c. (under the skin) injection
glimepirideDrug
8 mg capsule
liraglutideDrug
1.2 mg for s.c. (under the skin) injection
placeboDrug
Glimepiride placebo, 8mg capsule
placeboDrug
Liraglutide placebo, 200 mcl
placeboDrug
Liraglutide placebo, 300 mcl

Study groups in NCT00294723
Study group	Role	What they receive
Lira 1.8	Experimental	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). Receives: Drug: liraglutide; Drug: placebo
Lira 1.2	Experimental	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). Receives: Drug: liraglutide; Drug: placebo
Glimepiride - 1	Active comparator	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). Receives: Drug: glimepiride; Drug: placebo
Glimepiride - 2	Active comparator	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). Receives: Drug: glimepiride; Drug: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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)
Measured: 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)
Measured: 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
Measured: week 0, week 156

Secondary outcomes (14)

Change in Body Weight at Week 52
Change in body weight from baseline (week 0) to 52 weeks (end of double-blind period)
Measured: 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)
Measured: week 0, week 104
Change in Body Weight at Week 156
Change in body weight from baseline (week 0) to 156 weeks
Measured: 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)
Measured: 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)
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: weeks 104-195

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 2006Nov 2008

First posted22 Feb 2006 (estimated)
Study startFeb 2006
Primary completionNov 2008
Study completionNov 2008

Why it stopped: The trial was terminated at week 195 due to an insufficient number of subjects remaining to obtain reasonable statistical power

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (19)Papers the sponsor has linked to this study.
Other trials for DiabetesStudies of the same condition, open and under way.
More trials run by Novo Nordisk A/SThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 746 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00294723
Sponsor's protocol ID: NN2211-1573
Acronym: LEAD-3
Status last verified: Jan 2017
First submitted: 20 Feb 2006
Last updated: 7 Mar 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 18819705
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.
PubMed 19245711
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.
PubMed 19491536
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.
PubMed 19878259
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.
PubMed 19930006
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.
PubMed 20590735
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.
PubMed 21450987
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.
PubMed 22055210
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.
PubMed 22193143
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.
PubMed 22174428
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.
PubMed 21883806
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.
PubMed 22862847
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.
PubMed 23010561
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.
PubMed 23186975
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.
PubMed 25504028

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 7 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Liraglutide Effect and Action in Diabetes (LEAD-3): Effect on Glycemic Control of Liraglutide Versus Glimepiride in Type 2 Diabetes
ClinicalTrials.gov ID: NCT00294723
Acronym / sponsor ID: LEAD-3 / NN2211-1573
Conditions: Diabetes, Diabetes Mellitus, Type 2
Phase: Phase 3
Study type: Interventional
Recruitment status: TerminatedReason stopped: The trial was terminated at week 195 due to an insufficient number of subjects remaining to obtain reasonable statistical power
Enrolment: 746 participants (actual)
Lead sponsor: Novo Nordisk A/SIndustry (pharma, biotech, devices)
Study start: Feb 2006
Primary completion: Nov 2008 (actual)
Study completion: Nov 2008 (actual)
First posted: 22 Feb 2006 (estimated)
Results: Posted 12 Mar 2010

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This trial is conducted in North America (the United States of America (USA) and Mexico).

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 4

Arm	Type	Receives
Lira 1.8	Experimental	Drug: liraglutide, Drug: placeboLiraglutide 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).
Lira 1.2	Experimental	Drug: liraglutide, Drug: placeboLiraglutide 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).
Glimepiride - 1	Active comparator	Drug: glimepiride, Drug: placeboGlimepiride 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).
Glimepiride - 2	Active comparator	Drug: glimepiride, Drug: placeboGlimepiride 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).

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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

Key exclusion criteria (3 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
liraglutide1.8 mg for s.c. (under the skin) injection	Drug	Lira 1.8
glimepiride8 mg capsule	Drug	Glimepiride - 1, Glimepiride - 2
liraglutide1.2 mg for s.c. (under the skin) injection	Drug	Lira 1.2
placeboGlimepiride placebo, 8mg capsule	Drug	Lira 1.2, Lira 1.8
placeboLiraglutide placebo, 200 mcl	Drug	Glimepiride - 1
placeboLiraglutide placebo, 300 mcl	Drug	Glimepiride - 2

Primary outcome

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

14 secondary outcomes

Change in Body Weight at Week 52
Time frame: week 0, week 52
Change in Body Weight at Week 104
Time frame: week 0, week 104
Change in Body Weight at Week 156
Time frame: week 0, week 156
Change in Fasting Plasma Glucose at Week 52
Time frame: week 0, week 52
Change in Fasting Plasma Glucose at Week 104
Time frame: week 0, week 104
Change in Fasting Plasma Glucose at Week 156
Time frame: week 0, week 156
Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 52
Time frame: week 0, week 52
Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 104
Time frame: week 0, week 104
Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 156
Time frame: week 0, week 156
Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 52
Time frame: week 0, week 52
Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 104
Time frame: week 0, week 104
Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 156
Time frame: week 0, week 156
Hypoglycaemic Episodes
Time frame: weeks 0-104
Hypoglycaemic Episodes
Time frame: weeks 104-195

Results and safety

Results posted to the registry on 12 Mar 2010, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Lira 1.8	247	173
Lira 1.2	251	162
Glimepiride	248	152

Primary outcome: Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 52

Time frame: week 0, week 52. Least squares mean (Standard Error). Unit: percentage point of total HbA1c

Measure	Lira 1.8 n = 234	Lira 1.2 n = 236	Glimepiride n = 241
Value	-1.14 (0.08)	-0.84 (0.08)	-0.51 (0.08)

Lira 1.8 vs Glimepiride: Estimated treatment difference, LS Mean: -0.62 (95% CI -0.83 to -0.42), p <0.0001, ANCOVA
Lira 1.2 vs Glimepiride: Estimated treatment difference, LS Mean: -0.33 (95% CI -0.53 to -0.13), p = 0.0014, ANCOVA
Lira 1.8 vs Lira 1.2: Estimated treatment difference, LS Mean: -0.29 (95% CI -0.50 to -0.09), p = 0.0046, ANCOVA

Population analysed: Intention to treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who had been exposed to at least one dose of the study products.

Primary outcome: Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 104

Time frame: week 0, week 104. Least squares mean (Standard Error). Unit: percentage point of total HbA1c

Measure	Lira 1.8 n = 234	Lira 1.2 n = 236	Glimepiride n = 241
Value	-0.88 (0.09)	-0.59 (0.09)	-0.28 (0.09)

Lira 1.8 vs Glimepiride: Estimated treatment difference, LS Mean: -0.60 (95% CI -0.83 to -0.38), p <.0001, ANCOVA
Lira 1.2 vs Glimepiride: Estimated treatment difference, LS Mean: -0.31 (95% CI -0.54 to -0.08), p = 0.0076, ANCOVA
Lira 1.8 vs Lira 1.2: Estimated treatment difference, LS Mean: -0.29 (95% CI -0.52 to -0.06), p = 0.0129, ANCOVA

Population analysed: Intention to treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who had been exposed to at least one dose of the study products.

Primary outcome: Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 156

Time frame: week 0, week 156. Least squares mean (Standard Error). Unit: percentage point of total HbA1c

Measure	Lira 1.8 n = 234	Lira 1.2 n = 236	Glimepiride n = 241
Value	-0.71 (0.09)	-0.44 (0.09)	-0.16 (0.08)

Lira 1.8 vs Glimepiride: Estimated treatment difference, LS Mean: -0.55 (95% CI -0.77 to -0.34), p <0.0001, ANCOVA
Lira 1.2 vs Glimepiride: Estimated treatment difference, LS Mean: -0.28 (95% CI -0.49 to -0.06), p = 0.0122, ANCOVA
Lira 1.8 vs Lira 1.2: Estimated treatment difference, LS Mean: -0.28 (95% CI -0.49 to -0.06), p = 0.0123, ANCOVA

Population analysed: Intention to treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who had been exposed to at least one dose of the study products.

14 secondary outcomes are reported in the full results.

Adverse events

Time frame: The adverse events were collected in a time span of 195 weeks.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Lira 1.8 (Weeks 0-104)	22 of 246 (8.9%)	183 of 246 (74.4%)	Not reported
Lira 1.2 (Weeks 0-104)	23 of 251 (9.2%)	181 of 251 (72.1%)	Not reported
Glimepiride (Weeks 0-104)	20 of 248 (8.1%)	148 of 248 (59.7%)	Not reported
Lira 1.8 (Weeks 104-195)	5 of 62 (8.1%)	40 of 62 (64.5%)	Not reported
Lira 1.2 (Weeks 104-195)	1 of 53 (1.9%)	37 of 53 (69.8%)	Not reported
Glimepiride (Weeks 104-195)	2 of 28 (7.1%)	13 of 28 (46.4%)	Not reported

Limitations and caveats (from the sponsor): Trial terminated due to an insufficient number of subjects remaining to obtain reasonable statistical power. Efficacy data was not analysed after week 156. Safety data was collected through week 195. No data was available from week 195 to 260

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 18819705Garber 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.
Results publication: PubMed 19245711Sullivan 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.
Results publication: PubMed 19491536McGill 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.
Results publication: PubMed 19878259Blonde 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.
Results publication: PubMed 19930006Jendle 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.
Results publication: PubMed 20590735Bode 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.
Results publication: PubMed 21450987Buse 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.
Results publication: PubMed 22055210Bode 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.
Results publication: PubMed 22193143Henry 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.
Results publication: PubMed 22174428Ingwersen 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.
Results publication: PubMed 21883806Zinman 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.
Results publication: PubMed 22862847Niswender 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.
Clinical Trials at Novo NordiskLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Global Clinical Registry (GCR, 1452) study director

Novo Nordisk A/S

117 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing liraglutide and glimepiride in people with Diabetes and Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 117 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 7 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 117 sites in United States, Mexico, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Mar 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 52 (time frame: week 0, week 52). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00294723, which also lists 19 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Mar 2017.