Clinical trial NCT00294723: To Evaluate the Effect of Liraglutide Versus Glimepiride (Amaryl®) on Haemoglobin A1c
Official title: Liraglutide Effect and Action in Diabetes (LEAD-3): Effect on Glycemic Control of Liraglutide Versus Glimepiride in Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Diabetes
Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2006-02-22
Enrollment: 746
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. 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).


Eligibility criteria: 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

Primary outcomes:
measure: Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 52
timeFrame: week 0, week 52
measure: Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 104
timeFrame: week 0, week 104
measure: Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 156
timeFrame: week 0, week 156
Secondary outcomes:
measure: Change in Body Weight at Week 52
timeFrame: week 0, week 52
measure: Change in Body Weight at Week 104
timeFrame: week 0, week 104
measure: Change in Body Weight at Week 156
timeFrame: week 0, week 156
measure: Change in Fasting Plasma Glucose at Week 52
timeFrame: week 0, week 52
measure: Change in Fasting Plasma Glucose at Week 104
timeFrame: week 0, week 104
measure: Change in Fasting Plasma Glucose at Week 156
timeFrame: week 0, week 156
measure: Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 52
timeFrame: week 0, week 52
measure: Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 104
timeFrame: week 0, week 104
measure: Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 156
timeFrame: week 0, week 156
measure: Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 52
timeFrame: week 0, week 52
measure: Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 104
timeFrame: week 0, week 104
measure: Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 156
timeFrame: week 0, week 156
measure: Hypoglycaemic Episodes
timeFrame: weeks 0-104
measure: Hypoglycaemic Episodes
timeFrame: weeks 104-195
Other outcomes:
Locations:
city: Concord
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Escondido
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Fullerton
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Inglewood
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Mission Viejo
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Orange
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Santa Barbara
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Spring Valley
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Vista
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Walnut Creek
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Daytona Beach
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Delray Beach
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Longwood
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Ocala
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: St. Cloud
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Athens
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Atlanta
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Atlanta
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Atlanta
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Atlanta
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Blue Ridge
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Columbus
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Marietta
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Powder Springs
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Tucker
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Honolulu
country: United States
facility: Novo Nordisk Investigational Site
state: Hawaii
city: Chicago
country: United States
facility: Novo Nordisk Investigational Site
state: Illinois
city: Chicago
country: United States
facility: Novo Nordisk Investigational Site
state: Illinois
city: Maywood
country: United States
facility: Novo Nordisk Investigational Site
state: Illinois
city: Indianapolis
country: United States
facility: Novo Nordisk Investigational Site
state: Indiana
city: Des Moines
country: United States
facility: Novo Nordisk Investigational Site
state: Iowa
city: Shawnee Mission
country: United States
facility: Novo Nordisk Investigational Site
state: Kansas
city: Topeka
country: United States
facility: Novo Nordisk Investigational Site
state: Kansas
city: Lexington
country: United States
facility: Novo Nordisk Investigational Site
state: Kentucky
city: Lexington
country: United States
facility: Novo Nordisk Investigational Site
state: Kentucky
city: New Orleans
country: United States
facility: Novo Nordisk Investigational Site
state: Louisiana
city: Baltimore
country: United States
facility: Novo Nordisk Investigational Site
state: Maryland
city: Hyattsville
country: United States
facility: Novo Nordisk Investigational Site
state: Maryland
city: Minneapolis
country: United States
facility: Novo Nordisk Investigational Site
state: Minnesota
city: St. Paul
country: United States
facility: Novo Nordisk Investigational Site
state: Minnesota
city: Jackson
country: United States
facility: Novo Nordisk Investigational Site
state: Mississippi
city: Tupelo
country: United States
facility: Novo Nordisk Investigational Site
state: Mississippi
city: Chesterfield
country: United States
facility: Novo Nordisk Investigational Site
state: Missouri
city: St. Louis
country: United States
facility: Novo Nordisk Investigational Site
state: Missouri
city: St. Louis
country: United States
facility: Novo Nordisk Investigational Site
state: Missouri
city: St. Peters
country: United States
facility: Novo Nordisk Investigational Site
state: Missouri
city: Butte
country: United States
facility: Novo Nordisk Investigational Site
state: Montana
city: Omaha
country: United States
facility: Novo Nordisk Investigational Site
state: Nebraska
city: Reno
country: United States
facility: Novo Nordisk Investigational Site
state: Nevada
city: Berlin
country: United States
facility: Novo Nordisk Investigational Site
state: New Jersey
city: Lawrenceville
country: United States
facility: Novo Nordisk Investigational Site
state: New Jersey
city: Plainsboro
country: United States
facility: Novo Nordisk Investigational Site
state: New Jersey
city: Albany
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Lewiston
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: New York
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Northport
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Staten Island
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Syracuse
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: West Seneca
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Asheville
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Charlotte
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Durham
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Greensboro
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Cleveland
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Dayton
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Mentor
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: Novo Nordisk Investigational Site
state: Oklahoma
city: Oklahoma City
country: United States
facility: Novo Nordisk Investigational Site
state: Oklahoma
city: Tulsa
country: United States
facility: Novo Nordisk Investigational Site
state: Oklahoma
city: Bend
country: United States
facility: Novo Nordisk Investigational Site
state: Oregon
city: Eugene
country: United States
facility: Novo Nordisk Investigational Site
state: Oregon
city: Medford
country: United States
facility: Novo Nordisk Investigational Site
state: Oregon
city: Medford
country: United States
facility: Novo Nordisk Investigational Site
state: Oregon
city: Lancaster
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Norristown
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: East Providence
country: United States
facility: Novo Nordisk Investigational Site
state: Rhode Island
city: Greer
country: United States
facility: Novo Nordisk Investigational Site
state: South Carolina
city: Spartanburg
country: United States
facility: Novo Nordisk Investigational Site
state: South Carolina
city: Chattanooga
country: United States
facility: Novo Nordisk Investigational Site
state: Tennessee
city: Arlington
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Corpus Christi
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Dallas
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Dallas
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Dallas
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Dallas
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Dallas
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Houston
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Houston
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Houston
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Houston
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Midland
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Salt Lake City
country: United States
facility: Novo Nordisk Investigational Site
state: Utah
city: Richmond
country: United States
facility: Novo Nordisk Investigational Site
state: Virginia
city: Edmonds
country: United States
facility: Novo Nordisk Investigational Site
state: Washington
city: Olympia
country: United States
facility: Novo Nordisk Investigational Site
state: Washington
city: Renton
country: United States
facility: Novo Nordisk Investigational Site
state: Washington
city: Spokane
country: United States
facility: Novo Nordisk Investigational Site
state: Washington
city: Tacoma
country: United States
facility: Novo Nordisk Investigational Site
state: Washington
city: Guadalajara
country: Mexico
facility: Novo Nordisk Investigational Site
state: Jalisco
city: Cuernavaca
country: Mexico
facility: Novo Nordisk Investigational Site
state: Morelos
city: Monterrey
country: Mexico
facility: Novo Nordisk Investigational Site
state: Nuevo León
city: Chihuahua, Chih
country: Mexico
facility: Novo Nordisk Investigational Site
city: Ciudad de México, D.F.
country: Mexico
facility: Novo Nordisk Investigational Site
city: Ciudad de México, D.F.
country: Mexico
facility: Novo Nordisk Investigational Site
city: Guadalajara
country: Mexico
facility: Novo Nordisk Investigational Site
city: Hermosillo, Son.
country: Mexico
facility: Novo Nordisk Investigational Site
city: Mexico D.F.
country: Mexico
facility: Novo Nordisk Investigational Site
city: Mexico, D.F.
country: Mexico
facility: Novo Nordisk Investigational Site
city: Monterrey, N.L.
country: Mexico
facility: Novo Nordisk Investigational Site
city: Monterrey, NL
country: Mexico
facility: Novo Nordisk Investigational Site
city: Santiago de Querétaro, Qro.
country: Mexico
facility: Novo Nordisk Investigational Site
city: Tampico
country: Mexico
facility: Novo Nordisk Investigational Site
city: Rio Piedras
country: Puerto Rico
facility: Novo Nordisk Investigational Site
Study officials:
affiliation: Novo Nordisk A/S
name: Global Clinical Registry (GCR, 1452)
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.