Clinical trial NCT00331851: Effect of Liraglutide on Blood Glucose Control in Subjects With Type 2 Diabetes
Official title: Liraglutide Effect and Action in Diabetes (LEAD-5): Effect on Glycaemic Control After Once Daily Administration of Liraglutide in Combination With Glimepiride and Metformin Versus Glimepiride and Metformin Combination Therapy, and Versus Insulin Glargine Added to Glimepiride and Metformin Combination Therapy in Subjects With Type 2 Diabetes.A Six-month Randomised, Double-blind, Parallel-group, Multi-centre, Multi-national Trial With an Open-label Treat-to-target Insulin Glargine Control Arm.
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: 2006-05-31
Enrollment: 584
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 Africa, Asia, Europe and South America. This trial is designed to show the effect of treatment with liraglutide added to existing glimepiride and metformin combination therapy and to compare it with the effects of insulin glargine added to combination therapy of glimepiride and metformin.


Eligibility criteria: Inclusion Criteria:

* Type 2 diabetes
* Treatment with oral anti-diabetic drugs for at least 3 months
* HbA1c: 7.5-10.0 % (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 kg/m2

Exclusion Criteria:

* Treatment with insulin within the last 3 months
* Treatment with any drug that could interfere with the glucose level
* Any serious medical condition
* Females who are pregnant, have 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: Glycaemic control
Other outcomes:
Locations:
city: Bahía Blanca
country: Argentina
facility: Novo Nordisk Investigational Site
city: Ciudad Autonoma de Bs As
country: Argentina
facility: Novo Nordisk Investigational Site
city: Junín
country: Argentina
facility: Novo Nordisk Investigational Site
city: Mendoza
country: Argentina
facility: Novo Nordisk Investigational Site
city: Rosario
country: Argentina
facility: Novo Nordisk Investigational Site
city: Bregenz
country: Austria
facility: Novo Nordisk Investigational Site
city: Wien
country: Austria
facility: Novo Nordisk Investigational Site
city: Wien
country: Austria
facility: Novo Nordisk Investigational Site
city: Wien
country: Austria
facility: Novo Nordisk Investigational Site
city: Wien
country: Austria
facility: Novo Nordisk Investigational Site
city: Wien
country: Austria
facility: Novo Nordisk Investigational Site
city: Wien
country: Austria
facility: Novo Nordisk Investigational Site
city: Curitiba
country: Brazil
facility: Novo Nordisk Investigational Site
city: Rio de Janeiro
country: Brazil
facility: Novo Nordisk Investigational Site
city: Rio de Janeiro
country: Brazil
facility: Novo Nordisk Investigational Site
city: San Paulo
country: Brazil
facility: Novo Nordisk Investigational Site
city: Sao Paulo
country: Brazil
facility: Novo Nordisk Investigational Site
city: São Paulo
country: Brazil
facility: Novo Nordisk Investigational Site
city: Esbjerg
country: Denmark
facility: Novo Nordisk Investigational Site
city: Gentofte
country: Denmark
facility: Novo Nordisk Investigational Site
city: Hellerup
country: Denmark
facility: Novo Nordisk Investigational Site
city: Hillerød
country: Denmark
facility: Novo Nordisk Investigational Site
city: Roskilde
country: Denmark
facility: Novo Nordisk Investigational Site
city: Slagelse
country: Denmark
facility: Novo Nordisk Investigational Site
city: Århus C
country: Denmark
facility: Novo Nordisk Investigational Site
city: Helsinki
country: Finland
facility: Novo Nordisk Investigational Site
city: Helsinki
country: Finland
facility: Novo Nordisk Investigational Site
city: Kuopio
country: Finland
facility: Novo Nordisk Investigational Site
city: Oulu
country: Finland
facility: Novo Nordisk Investigational Site
city: Turku
country: Finland
facility: Novo Nordisk Investigational Site
city: Belgrade
country: Former Serbia and Montenegro
facility: Novo Nordisk Investigational Site
city: Nis
country: Former Serbia and Montenegro
facility: Novo Nordisk Investigational Site
city: Besancon
country: France
facility: Novo Nordisk Investigational Site
city: Brest
country: France
facility: Novo Nordisk Investigational Site
city: Corbeil Essonnes
country: France
facility: Novo Nordisk Investigational Site
city: DIJON cedex
country: France
facility: Novo Nordisk Investigational Site
city: LA ROCHELLE cedex
country: France
facility: Novo Nordisk Investigational Site
city: Nanterre
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: Venissieux
country: France
facility: Novo Nordisk Investigational Site
city: Hyderabad
country: India
facility: Novo Nordisk Investigational Site
state: Andhra Pradesh
city: Karnal
country: India
facility: Novo Nordisk Investigational Site
state: Haryana
city: Pune
country: India
facility: Novo Nordisk Investigational Site
state: Maharashtra
city: Hyderabad
country: India
facility: Novo Nordisk Investigational Site
city: Patna
country: India
facility: Novo Nordisk Investigational Site
city: Bergamo
country: Italy
facility: Novo Nordisk Investigational Site
city: Bologna
country: Italy
facility: Novo Nordisk Investigational Site
city: Catania
country: Italy
facility: Novo Nordisk Investigational Site
city: Catanzaro
country: Italy
facility: Novo Nordisk Investigational Site
city: Chieri
country: Italy
facility: Novo Nordisk Investigational Site
city: Chieti Scalo
country: Italy
facility: Novo Nordisk Investigational Site
city: Messina
country: Italy
facility: Novo Nordisk Investigational Site
city: Padova
country: Italy
facility: Novo Nordisk Investigational Site
city: Parma
country: Italy
facility: Novo Nordisk Investigational Site
city: Siena
country: Italy
facility: Novo Nordisk Investigational Site
city: Almere
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Den Haag
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Den Helder
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Eindhoven
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Gouda
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Maastricht
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Zevenaar
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Zoetermeer
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Bergen
country: Norway
facility: Novo Nordisk Investigational Site
city: Gjettum
country: Norway
facility: Novo Nordisk Investigational Site
city: Jessheim
country: Norway
facility: Novo Nordisk Investigational Site
city: Nordbyhagen
country: Norway
facility: Novo Nordisk Investigational Site
city: Notodden
country: Norway
facility: Novo Nordisk Investigational Site
city: Sandvika
country: Norway
facility: Novo Nordisk Investigational Site
city: Skedsmokorset
country: Norway
facility: Novo Nordisk Investigational Site
city: Cebu City
country: Philippines
facility: Novo Nordisk Investigational Site
city: Manila
country: Philippines
facility: Novo Nordisk Investigational Site
city: Marikina City
country: Philippines
facility: Novo Nordisk Investigational Site
city: Pasig City
country: Philippines
facility: Novo Nordisk Investigational Site
city: Gdynia
country: Poland
facility: Novo Nordisk Investigational Site
city: Katowice
country: Poland
facility: Novo Nordisk Investigational Site
city: Opole
country: Poland
facility: Novo Nordisk Investigational Site
city: Poznan
country: Poland
facility: Novo Nordisk Investigational Site
city: Wroclaw
country: Poland
facility: Novo Nordisk Investigational Site
city: Zabrze
country: Poland
facility: Novo Nordisk Investigational Site
city: Moscow
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Moscow
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Moscow
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Banska Bystrica
country: Slovakia
facility: Novo Nordisk Investigational Site
city: Bratislava
country: Slovakia
facility: Novo Nordisk Investigational Site
city: L'ubochna
country: Slovakia
facility: Novo Nordisk Investigational Site
city: Martin
country: Slovakia
facility: Novo Nordisk Investigational Site
city: Nitra
country: Slovakia
facility: Novo Nordisk Investigational Site
city: Zilina
country: Slovakia
facility: Novo Nordisk Investigational Site
city: Bloemfontein
country: South Africa
facility: Novo Nordisk Investigational Site
state: Free State
city: Pretoria
country: South Africa
facility: Novo Nordisk Investigational Site
state: Gauteng
city: Pretoria
country: South Africa
facility: Novo Nordisk Investigational Site
state: Gauteng
city: Worcester
country: South Africa
facility: Novo Nordisk Investigational Site
state: Western Cape
city: Baracaldo
country: Spain
facility: Novo Nordisk Investigational Site
city: Barcelona
country: Spain
facility: Novo Nordisk Investigational Site
city: Getafe
country: Spain
facility: Novo Nordisk Investigational Site
city: Málaga
country: Spain
facility: Novo Nordisk Investigational Site
city: Santiago de Compostela
country: Spain
facility: Novo Nordisk Investigational Site
city: Sevilla
country: Spain
facility: Novo Nordisk Investigational Site
city: Valencia
country: Spain
facility: Novo Nordisk Investigational Site
city: Valencia
country: Spain
facility: Novo Nordisk Investigational Site
city: Valencia
country: Spain
facility: Novo Nordisk Investigational Site
city: Valladolid
country: Spain
facility: Novo Nordisk Investigational Site
city: Ayr
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Bradford
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Guildford
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Liverpool
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Livingstone
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Llantrisant
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Manchester
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Nottingham
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Salford
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Sheffield
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Swansea
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Watford
country: United Kingdom
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: 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: Russell-Jones D, Vaag A, Schmitz O, Sethi BK, Lalic N, Antic S, Zdravkovic M, Ravn GM, Simo R; Liraglutide Effect and Action in Diabetes 5 (LEAD-5) met+SU Study Group. Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): a randomised controlled trial. Diabetologia. 2009 Oct;52(10):2046-55. doi: 10.1007/s00125-009-1472-y. Epub 2009 Aug 14.
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: 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: Buse JB, Peters A, Russell-Jones D, Furber S, Donsmark M, Han J, MacConell L, Maggs D, Diamant M. Is insulin the most effective injectable antihyperglycaemic therapy? Diabetes Obes Metab. 2015 Feb;17(2):145-51. doi: 10.1111/dom.12402. Epub 2014 Nov 9.
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.