Clinical trial NCT00318422: Effect of Liraglutide on Blood Glucose Control in Subjects With Type 2 Diabetes
Official title: Liraglutide Effect and Action in Diabetes (LEAD-1): Effect on Glycaemic Control After Once Daily Administration of Liraglutide in Combination With Glimepiride Versus Glimepiride Monotherapy Versus Glimepiride and Rosiglitazone Combination Therapy in Subjects With Type 2 Diabetes.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes
Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2006-04-26
Enrollment: 1041
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 globally (the United States of America excepted). This trial is designed to show the effect of treatment with liraglutide when added to existing glimepiride therapy and to compare this to both glimepiride monotherapy and to rosiglitazone as add-on therapy to glimepiride.


Eligibility criteria: Inclusion Criteria:

* Type 2 diabetes
* Treatment with oral anti-diabetic drugs 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 to 45.0 kg/m2.

Exclusion Criteria:

* Treatment with insulin within the last three months
* Treatment with any drug that could interfere with the glucose level
* Any serious medical condition
* Females who are pregnant, have the intention of becoming pregnant or are breastfeeding

Primary outcomes:
measure: HbA1c
timeFrame: after 26 weeks of treatment
Secondary outcomes:
measure: body weight
measure: Safety and tolerability
measure: beta-cell function
measure: Glycemic control parameters (fasting plasma glucose, -glucose profiles)
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Novo Nordisk Investigational Site
city: Buenos Aires
country: Argentina
facility: Novo Nordisk Investigational Site
city: Buenos Aires
country: Argentina
facility: Novo Nordisk Investigational Site
city: Córdoba
country: Argentina
facility: Novo Nordisk Investigational Site
city: Mar del Plata
country: Argentina
facility: Novo Nordisk Investigational Site
city: Mendoza
country: Argentina
facility: Novo Nordisk Investigational Site
city: Woolloongabba
country: Australia
facility: Novo Nordisk Investigational Site
state: Queensland
city: Melbourne
country: Australia
facility: Novo Nordisk Investigational Site
state: Victoria
city: Caboolture
country: Australia
facility: Novo Nordisk Investigational Site
city: Ingleburn
country: Australia
facility: Novo Nordisk Investigational Site
city: Kippa Ring
country: Australia
facility: Novo Nordisk Investigational Site
city: Miranda
country: Australia
facility: Novo Nordisk Investigational Site
city: Randwick
country: Australia
facility: Novo Nordisk Investigational Site
city: Southport
country: Australia
facility: Novo Nordisk Investigational Site
city: Stones Corner
country: Australia
facility: Novo Nordisk Investigational Site
city: Fortaleza
country: Brazil
facility: Novo Nordisk Investigational Site
city: Sao Paulo
country: Brazil
facility: Novo Nordisk Investigational Site
city: Pleven
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Plovdiv
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Russe
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Sofia
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Sofia
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Varna
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Osijek
country: Croatia
facility: Novo Nordisk Investigational Site
city: Slavonski Brod
country: Croatia
facility: Novo Nordisk Investigational Site
city: Split
country: Croatia
facility: Novo Nordisk Investigational Site
city: Brno
country: Czech Republic
facility: Novo Nordisk Investigational Site
city: Hradec Králové
country: Czech Republic
facility: Novo Nordisk Investigational Site
city: Ostrava
country: Czech Republic
facility: Novo Nordisk Investigational Site
city: Plzen - Lochotin
country: Czech Republic
facility: Novo Nordisk Investigational Site
city: Prague 4
country: Czech Republic
facility: Novo Nordisk Investigational Site
city: Praha 10
country: Czech Republic
facility: Novo Nordisk Investigational Site
city: Praha 5
country: Czech Republic
facility: Novo Nordisk Investigational Site
city: Espoo
country: Finland
facility: Novo Nordisk Investigational Site
city: Helsinki
country: Finland
facility: Novo Nordisk Investigational Site
city: Lahti
country: Finland
facility: Novo Nordisk Investigational Site
city: Nurmijärvi
country: Finland
facility: Novo Nordisk Investigational Site
city: Oulu
country: Finland
facility: Novo Nordisk Investigational Site
city: Pieksämäki
country: Finland
facility: Novo Nordisk Investigational Site
city: Rauma
country: Finland
facility: Novo Nordisk Investigational Site
city: Rovaniemi
country: Finland
facility: Novo Nordisk Investigational Site
city: Tampere
country: Finland
facility: Novo Nordisk Investigational Site
city: Tampere
country: Finland
facility: Novo Nordisk Investigational Site
city: DAX
country: France
facility: Novo Nordisk Investigational Site
city: LA ROCHELLE cedex
country: France
facility: Novo Nordisk Investigational Site
city: Montpellier
country: France
facility: Novo Nordisk Investigational Site
city: Mougins
country: France
facility: Novo Nordisk Investigational Site
city: Narbonne
country: France
facility: Novo Nordisk Investigational Site
city: NEVERS cedex
country: France
facility: Novo Nordisk Investigational Site
city: Paris
country: France
facility: Novo Nordisk Investigational Site
city: Rennes
country: France
facility: Novo Nordisk Investigational Site
city: Saint Mandé
country: France
facility: Novo Nordisk Investigational Site
city: Athens
country: Greece
facility: Novo Nordisk Investigational Site
city: Athens
country: Greece
facility: Novo Nordisk Investigational Site
city: Athens
country: Greece
facility: Novo Nordisk Investigational Site
city: Athens
country: Greece
facility: Novo Nordisk Investigational Site
city: Mumbai
country: India
facility: Novo Nordisk Investigational Site
state: Maharashtra
city: Chandigarh
country: India
facility: Novo Nordisk Investigational Site
state: Punjab
city: Chennai
country: India
facility: Novo Nordisk Investigational Site
city: Mumbai
country: India
facility: Novo Nordisk Investigational Site
city: Haifa
country: Israel
facility: Novo Nordisk Investigational Site
city: Jerusalem
country: Israel
facility: Novo Nordisk Investigational Site
city: Tel Hashomer
country: Israel
facility: Novo Nordisk Investigational Site
city: Catania
country: Italy
facility: Novo Nordisk Investigational Site
city: Lucca
country: Italy
facility: Novo Nordisk Investigational Site
city: Milano
country: Italy
facility: Novo Nordisk Investigational Site
city: Napoli
country: Italy
facility: Novo Nordisk Investigational Site
city: Perugia
country: Italy
facility: Novo Nordisk Investigational Site
city: Ravenna
country: Italy
facility: Novo Nordisk Investigational Site
city: Roma
country: Italy
facility: Novo Nordisk Investigational Site
city: Torino
country: Italy
facility: Novo Nordisk Investigational Site
city: Seoul
country: Korea, Republic of
facility: Novo Nordisk Investigational Site
city: Seoul
country: Korea, Republic of
facility: Novo Nordisk Investigational Site
city: Seoul
country: Korea, Republic of
facility: Novo Nordisk Investigational Site
city: Cheras
country: Malaysia
facility: Novo Nordisk Investigational Site
city: Kota Bharu, Kelantan
country: Malaysia
facility: Novo Nordisk Investigational Site
city: Pulau Pinang
country: Malaysia
facility: Novo Nordisk Investigational Site
city: Davao City
country: Philippines
facility: Novo Nordisk Investigational Site
city: Makati City
country: Philippines
facility: Novo Nordisk Investigational Site
city: Marikina City
country: Philippines
facility: Novo Nordisk Investigational Site
city: Quezon City
country: Philippines
facility: Novo Nordisk Investigational Site
city: Bytom
country: Poland
facility: Novo Nordisk Investigational Site
city: Gdansk
country: Poland
facility: Novo Nordisk Investigational Site
city: Gniewkowo
country: Poland
facility: Novo Nordisk Investigational Site
city: Kamieniec Zabkowicki
country: Poland
facility: Novo Nordisk Investigational Site
city: Krakow
country: Poland
facility: Novo Nordisk Investigational Site
city: Lodz
country: Poland
facility: Novo Nordisk Investigational Site
city: Lublin
country: Poland
facility: Novo Nordisk Investigational Site
city: Lublin
country: Poland
facility: Novo Nordisk Investigational Site
city: Mazowieckie
country: Poland
facility: Novo Nordisk Investigational Site
city: Nysa
country: Poland
facility: Novo Nordisk Investigational Site
city: Rawa Mazowiecka
country: Poland
facility: Novo Nordisk Investigational Site
city: Szczecin
country: Poland
facility: Novo Nordisk Investigational Site
city: Tychy
country: Poland
facility: Novo Nordisk Investigational Site
city: Warszawa
country: Poland
facility: Novo Nordisk Investigational Site
city: Zabrze
country: Poland
facility: Novo Nordisk Investigational Site
city: Ploiesti
country: Romania
facility: Novo Nordisk Investigational Site
state: Prahova
city: Baia Mare
country: Romania
facility: Novo Nordisk Investigational Site
city: Brasov
country: Romania
facility: Novo Nordisk Investigational Site
city: Bucharest
country: Romania
facility: Novo Nordisk Investigational Site
city: Timisoara
country: Romania
facility: Novo Nordisk Investigational Site
city: Johannesburg
country: South Africa
facility: Novo Nordisk Investigational Site
state: Gauteng
city: Johannesburg
country: South Africa
facility: Novo Nordisk Investigational Site
state: Gauteng
city: Johannesburg
country: South Africa
facility: Novo Nordisk Investigational Site
state: Gauteng
city: Durban
country: South Africa
facility: Novo Nordisk Investigational Site
state: KwaZulu-Natal
city: Umhlanga
country: South Africa
facility: Novo Nordisk Investigational Site
city: Gijón
country: Spain
facility: Novo Nordisk Investigational Site
city: Palma de Mallorca
country: Spain
facility: Novo Nordisk Investigational Site
city: Reus
country: Spain
facility: Novo Nordisk Investigational Site
city: Bern
country: Switzerland
facility: Novo Nordisk Investigational Site
city: Lausanne
country: Switzerland
facility: Novo Nordisk Investigational Site
city: St. Gallen
country: Switzerland
facility: Novo Nordisk Investigational Site
city: Zürich
country: Switzerland
facility: Novo Nordisk Investigational Site
city: Zürich
country: Switzerland
facility: Novo Nordisk Investigational Site
city: Changhua
country: Taiwan
facility: Novo Nordisk Investigational Site
city: Kaohsiung City
country: Taiwan
facility: Novo Nordisk Investigational Site
city: Taipei
country: Taiwan
facility: Novo Nordisk Investigational Site
city: Taipei
country: Taiwan
facility: Novo Nordisk Investigational Site
city: Bangkok
country: Thailand
facility: Novo Nordisk Investigational Site
city: Bangkok
country: Thailand
facility: Novo Nordisk Investigational Site
city: Bangkok
country: Thailand
facility: Novo Nordisk Investigational Site
city: Ankara
country: Turkey
facility: Novo Nordisk Investigational Site
city: Antalya
country: Turkey
facility: Novo Nordisk Investigational Site
city: Istanbul
country: Turkey
facility: Novo Nordisk Investigational Site
city: Istanbul
country: Turkey
facility: Novo Nordisk Investigational Site
city: Istanbul
country: Turkey
facility: Novo Nordisk Investigational Site
city: Izmir
country: Turkey
facility: Novo Nordisk Investigational Site
Study officials:
affiliation: Novo Nordisk A/S
name: Global Clinical Registry (GCR, 1452)
role: STUDY_DIRECTOR
References:
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: Marre M, Shaw J, Brandle M, Bebakar WM, Kamaruddin NA, Strand J, Zdravkovic M, Le Thi TD, Colagiuri S; LEAD-1 SU study group. Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with Type 2 diabetes (LEAD-1 SU). Diabet Med. 2009 Mar;26(3):268-78. doi: 10.1111/j.1464-5491.2009.02666.x.
citation: Nauck M, Marre M. Adding liraglutide to oral antidiabetic drug monotherapy: efficacy and weight benefits. Postgrad Med. 2009 May;121(3):5-15. doi: 10.3810/pgm.2009.05.1997.
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: 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: 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.
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: 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.