Effect of Liraglutide on Blood Glucose Control in Subjects With Type 2 Diabetes (LEAD-1)

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.

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 1041
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, B1636DSU
    • Novo Nordisk Investigational Site
  • Buenos Aires, Argentina, C1425AGC
    • Novo Nordisk Investigational Site
  • Buenos Aires, Argentina, C1181ACH
    • Novo Nordisk Investigational Site
  • Córdoba, Argentina, 5000
    • Novo Nordisk Investigational Site
  • Mar del Plata, Argentina, B7602CBM
    • Novo Nordisk Investigational Site
  • Mendoza, Argentina, 5500
    • Novo Nordisk Investigational Site
• Australia
  • Caboolture, Australia, 4510
    • Novo Nordisk Investigational Site
  • Ingleburn, Australia, 2565
    • Novo Nordisk Investigational Site
  • Kippa Ring, Australia, 4021
    • Novo Nordisk Investigational Site
  • Miranda, Australia, 2228
    • Novo Nordisk Investigational Site
  • Randwick, Australia, 2031
    • Novo Nordisk Investigational Site
  • Southport, Australia, 4215
    • Novo Nordisk Investigational Site
  • Stones Corner, Australia, 4120
    • Novo Nordisk Investigational Site
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Novo Nordisk Investigational Site
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Novo Nordisk Investigational Site
• Brazil
  • Fortaleza, Brazil, 60120-021
    • Novo Nordisk Investigational Site
  • Sao Paulo, Brazil, 04022-001
    • Novo Nordisk Investigational Site
• Bulgaria
  • Pleven, Bulgaria, 5800
    • Novo Nordisk Investigational Site
  • Plovdiv, Bulgaria, 4002
    • Novo Nordisk Investigational Site
  • Russe, Bulgaria, 7000
    • Novo Nordisk Investigational Site
  • Sofia, Bulgaria, 1431
    • Novo Nordisk Investigational Site
  • Sofia, Bulgaria, 1606
    • Novo Nordisk Investigational Site
  • Varna, Bulgaria, 9010
    • Novo Nordisk Investigational Site
• Croatia
  • Osijek, Croatia, 31 000
    • Novo Nordisk Investigational Site
  • Slavonski Brod, Croatia, 35 000
    • Novo Nordisk Investigational Site
  • Split, Croatia, 21 000
    • Novo Nordisk Investigational Site
• Czech Republic
  • Brno, Czech Republic, 65691
    • Novo Nordisk Investigational Site
  • Hradec Králové, Czech Republic, 500 36
    • Novo Nordisk Investigational Site
  • Ostrava, Czech Republic, 70852
    • Novo Nordisk Investigational Site
  • Plzen - Lochotin, Czech Republic, 30460
    • Novo Nordisk Investigational Site
  • Prague 4, Czech Republic, 140 21
    • Novo Nordisk Investigational Site
  • Praha 10, Czech Republic, 10034
    • Novo Nordisk Investigational Site
  • Praha 5, Czech Republic, 15018
    • Novo Nordisk Investigational Site
• Finland
  • Espoo, Finland, 02740
    • Novo Nordisk Investigational Site
  • Helsinki, Finland, 00150
    • Novo Nordisk Investigational Site
  • Lahti, Finland, 15110
    • Novo Nordisk Investigational Site
  • Nurmijärvi, Finland, 01900
    • Novo Nordisk Investigational Site
  • Oulu, Finland, FI-90100
    • Novo Nordisk Investigational Site
  • Pieksämäki, Finland, 76100
    • Novo Nordisk Investigational Site
  • Rauma, Finland, 26100
    • Novo Nordisk Investigational Site
  • Rovaniemi, Finland, 96100
    • Novo Nordisk Investigational Site
  • Tampere, Finland, 33101
    • Novo Nordisk Investigational Site
  • Tampere, Finland, 33100
    • Novo Nordisk Investigational Site
• France
  • DAX, France, 40107
    • Novo Nordisk Investigational Site
  • LA ROCHELLE cedex, France, 17019
    • Novo Nordisk Investigational Site
  • Montpellier, France, 34295
    • Novo Nordisk Investigational Site
  • Mougins, France, 06250
    • Novo Nordisk Investigational Site
  • NEVERS cedex, France, 58033
    • Novo Nordisk Investigational Site
  • Narbonne, France, 11108
    • Novo Nordisk Investigational Site
  • Paris, France, 75877
    • Novo Nordisk Investigational Site
  • Rennes, France, 35056
    • Novo Nordisk Investigational Site
  • Saint Mandé, France, 94160
    • Novo Nordisk Investigational Site
• Greece
  • Athens, Greece, GR-11527
    • Novo Nordisk Investigational Site
  • Athens, Greece, 115 21
    • Novo Nordisk Investigational Site
  • Athens, Greece, 151 23
    • Novo Nordisk Investigational Site
  • Athens, Greece, GR-10552
    • Novo Nordisk Investigational Site
• India
  • Chennai, India, 600116
    • Novo Nordisk Investigational Site
  • Mumbai, India, 400 0067
    • Novo Nordisk Investigational Site
  • Maharashtra
    • Mumbai, Maharashtra, India, 4000021
      • Novo Nordisk Investigational Site
  • Punjab
    • Chandigarh, Punjab, India, 160012
      • Novo Nordisk Investigational Site
• Israel
  • Haifa, Israel, 31096
    • Novo Nordisk Investigational Site
  • Jerusalem, Israel, 91120
    • Novo Nordisk Investigational Site
  • Tel Hashomer, Israel, 52621
    • Novo Nordisk Investigational Site
• Italy
  • Catania, Italy, 95122
    • Novo Nordisk Investigational Site
  • Lucca, Italy, 55100
    • Novo Nordisk Investigational Site
  • Milano, Italy, 20132
    • Novo Nordisk Investigational Site
  • Napoli, Italy, 80138
    • Novo Nordisk Investigational Site
  • Perugia, Italy, 06126
    • Novo Nordisk Investigational Site
  • Ravenna, Italy, 48121
    • Novo Nordisk Investigational Site
  • Roma, Italy, 00189
    • Novo Nordisk Investigational Site
  • Torino, Italy, 10144
    • Novo Nordisk Investigational Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 08308
    • Novo Nordisk Investigational Site
  • Seoul, Korea, Republic of, 137-701
    • Novo Nordisk Investigational Site
  • Seoul, Korea, Republic of, 130-701
    • Novo Nordisk Investigational Site
• Malaysia
  • Cheras, Malaysia, 56000
    • Novo Nordisk Investigational Site
  • Kota Bharu, Kelantan, Malaysia, 16150
    • Novo Nordisk Investigational Site
  • Pulau Pinang, Malaysia, 10990
    • Novo Nordisk Investigational Site
• Philippines
  • Davao City, Philippines, 8000
    • Novo Nordisk Investigational Site
  • Makati City, Philippines, 1218
    • Novo Nordisk Investigational Site
  • Marikina City, Philippines, 1100
    • Novo Nordisk Investigational Site
  • Quezon City, Philippines, 1100
    • Novo Nordisk Investigational Site
• Poland
  • Bytom, Poland, 41-902
    • Novo Nordisk Investigational Site
  • Gdansk, Poland, 80-858
    • Novo Nordisk Investigational Site
  • Gniewkowo, Poland, 88-140
    • Novo Nordisk Investigational Site
  • Kamieniec Zabkowicki, Poland, 57-230
    • Novo Nordisk Investigational Site
  • Krakow, Poland, 31-455
    • Novo Nordisk Investigational Site
  • Lodz, Poland, 90-030
    • Novo Nordisk Investigational Site
  • Lublin, Poland, 20-538
    • Novo Nordisk Investigational Site
  • Lublin, Poland, 20-081
    • Novo Nordisk Investigational Site
  • Mazowieckie, Poland, 09-400
    • Novo Nordisk Investigational Site
  • Nysa, Poland, 48-300
    • Novo Nordisk Investigational Site
  • Rawa Mazowiecka, Poland, 96-200
    • Novo Nordisk Investigational Site
  • Szczecin, Poland, 71-455
    • Novo Nordisk Investigational Site
  • Tychy, Poland, 43-100
    • Novo Nordisk Investigational Site
  • Warszawa, Poland, 01-911
    • Novo Nordisk Investigational Site
  • Zabrze, Poland, 41-800
    • Novo Nordisk Investigational Site
• Romania
  • Baia Mare, Romania, 430032
    • Novo Nordisk Investigational Site
  • Brasov, Romania, 500269
    • Novo Nordisk Investigational Site
  • Bucharest, Romania, 020475
    • Novo Nordisk Investigational Site
  • Timisoara, Romania, 300736
    • Novo Nordisk Investigational Site
  • Prahova
    • Ploiesti, Prahova, Romania, 100097
      • Novo Nordisk Investigational Site
• South Africa
  • Umhlanga, South Africa, 4320
    • Novo Nordisk Investigational Site
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 1829
      • Novo Nordisk Investigational Site
    • Johannesburg, Gauteng, South Africa, 2001
      • Novo Nordisk Investigational Site
    • Johannesburg, Gauteng, South Africa, 2076
      • Novo Nordisk Investigational Site
  • KwaZulu-Natal
    • Durban, KwaZulu-Natal, South Africa, 4001
      • Novo Nordisk Investigational Site
• Spain
  • Gijón, Spain, 33206
    • Novo Nordisk Investigational Site
  • Palma de Mallorca, Spain, 07198
    • Novo Nordisk Investigational Site
  • Reus, Spain, 43201
    • Novo Nordisk Investigational Site
• Switzerland
  • Bern, Switzerland, 3010
    • Novo Nordisk Investigational Site
  • Lausanne, Switzerland, 1011
    • Novo Nordisk Investigational Site
  • St. Gallen, Switzerland, 9007
    • Novo Nordisk Investigational Site
  • Zürich, Switzerland, 8091
    • Novo Nordisk Investigational Site
  • Zürich, Switzerland, 8032
    • Novo Nordisk Investigational Site
• Taiwan
  • Changhua, Taiwan, 500
    • Novo Nordisk Investigational Site
  • Kaohsiung City, Taiwan, 833
    • Novo Nordisk Investigational Site
  • Taipei, Taiwan, 100
    • Novo Nordisk Investigational Site
  • Taipei, Taiwan, 231
    • Novo Nordisk Investigational Site
• Thailand
  • Bangkok, Thailand, 10400
    • Novo Nordisk Investigational Site
  • Bangkok, Thailand, 10330
    • Novo Nordisk Investigational Site
  • Bangkok, Thailand, 10110
    • Novo Nordisk Investigational Site
• Turkey
  • Ankara, Turkey, 06500
    • Novo Nordisk Investigational Site
  • Antalya, Turkey, 07059
    • Novo Nordisk Investigational Site
  • Istanbul, Turkey, 34390
    • Novo Nordisk Investigational Site
  • Istanbul, Turkey, 34718
    • Novo Nordisk Investigational Site
  • Istanbul, Turkey, 34890
    • Novo Nordisk Investigational Site
  • Izmir, Turkey, 35340
    • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Type 2 diabetes
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
HbA1c	after 26 weeks of treatment

Secondary Outcome Measures

Outcome Measure
Safety and tolerability
body weight
beta-cell function
Glycemic control parameters (fasting plasma glucose, -glucose profiles)

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• Henry RR, Buse JB, Sesti G, Davies MJ, Jensen KH, Brett J, Pratley RE. Efficacy of antihyperglycemic therapies and the influence of baseline hemoglobin A(1C): a meta-analysis of the liraglutide development program. Endocr Pract. 2011 Nov-Dec;17(6):906-13. doi: 10.4158/ep.17.6.906.
• Zinman B, Schmidt WE, Moses A, Lund N, Gough S. Achieving a clinically relevant composite outcome of an HbA1c of <7% without weight gain or hypoglycaemia in type 2 diabetes: a meta-analysis of the liraglutide clinical trial programme. Diabetes Obes Metab. 2012 Jan;14(1):77-82. doi: 10.1111/j.1463-1326.2011.01493.x. Epub 2011 Oct 30.
• Niswender K, Pi-Sunyer X, Buse J, Jensen KH, Toft AD, Russell-Jones D, Zinman B. Weight change with liraglutide and comparator therapies: an analysis of seven phase 3 trials from the liraglutide diabetes development programme. Diabetes Obes Metab. 2013 Jan;15(1):42-54. doi: 10.1111/j.1463-1326.2012.01673.x. Epub 2012 Sep 9.
• Alves C, Batel-Marques F, Macedo AF. A meta-analysis of serious adverse events reported with exenatide and liraglutide: acute pancreatitis and cancer. Diabetes Res Clin Pract. 2012 Nov;98(2):271-84. doi: 10.1016/j.diabres.2012.09.008. Epub 2012 Sep 23.
• King AB, Montanya E, Pratley RE, Blonde L, Svendsen CB, Donsmark M, Sesti G. Liraglutide achieves A1C targets more often than sitagliptin or exenatide when added to metformin in patients with type 2 diabetes and a baseline A1C <8.0%. Endocr Pract. 2013 Jan-Feb;19(1):64-72. doi: 10.4158/EP12232.OR.
• Jensen TM, Saha K, Steinberg WM. Is there a link between liraglutide and pancreatitis? A post hoc review of pooled and patient-level data from completed liraglutide type 2 diabetes clinical trials. Diabetes Care. 2015 Jun;38(6):1058-66. doi: 10.2337/dc13-1210. Epub 2014 Dec 12. Erratum In: Diabetes Care. 2015 Aug;38(8):1622.
• Sullivan SD, Alfonso-Cristancho R, Conner C, Hammer M, Blonde L. Long-term outcomes in patients with type 2 diabetes receiving glimepiride combined with liraglutide or rosiglitazone. Cardiovasc Diabetol. 2009 Feb 26;8:12. doi: 10.1186/1475-2840-8-12.
• McGill JB. Insights from the Liraglutide Clinical Development Program--the Liraglutide Effect and Action in Diabetes (LEAD) studies. Postgrad Med. 2009 May;121(3):16-25. doi: 10.3810/pgm.2009.05.1998.
• Buse JB, Garber A, Rosenstock J, Schmidt WE, Brett JH, Videbaek N, Holst J, Nauck M. Liraglutide treatment is associated with a low frequency and magnitude of antibody formation with no apparent impact on glycemic response or increased frequency of adverse events: results from the Liraglutide Effect and Action in Diabetes (LEAD) trials. J Clin Endocrinol Metab. 2011 Jun;96(6):1695-702. doi: 10.1210/jc.2010-2822. Epub 2011 Mar 30.
• Bode BW, Brett J, Falahati A, Pratley RE. Comparison of the efficacy and tolerability profile of liraglutide, a once-daily human GLP-1 analog, in patients with type 2 diabetes >/=65 and <65 years of age: a pooled analysis from phase III studies. Am J Geriatr Pharmacother. 2011 Dec;9(6):423-33. doi: 10.1016/j.amjopharm.2011.09.007. Epub 2011 Nov 4.
• 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.
• 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.
• 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.
• 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.
• 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.

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start: May 1, 2006
• Primary Completion (Actual): May 1, 2007
• Study Completion (Actual): May 1, 2007

Study Registration Dates

• First Submitted: April 25, 2006
• First Submitted That Met QC Criteria: April 25, 2006
• First Posted (Estimate): April 26, 2006

Study Record Updates

• Last Update Posted (Estimate): January 25, 2017
• Last Update Submitted That Met QC Criteria: January 24, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Anti-Arrhythmia Agents; Immunosuppressive Agents; Immunologic Factors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Liraglutide; Rosiglitazone; Glimepiride
• Other Study ID Numbers: NN2211-1436; 2005-003414-15 (EudraCT Number)