DiabetesPhase 3LEAD-2NCT00318461

To Compare the Effect of Liraglutide When Given Together With Metformin With the Effect of Metformin Given Alone and With the Effect of Glimepiride and Metformin Given Together

A Phase 3 study testing liraglutide, metformin and glimepiride in people with Diabetes and Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 190 sites in 20 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

This trial is conducted in Europe, Oceania, Africa, Asia and South America. This trial is designed to show the effect of treatment with liraglutide when adding to existing metformin therapy and to compare it with the effects of metformin monotherapy and combination therapy of metformin and glimepiride. 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, metformin 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: 1,091 participants
Where: 190 sitesin 20 countries
Study dates: May 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

Subjects diagnosed with type 2 diabetes and treated with oral anti-diabetic drugs (OADs) 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 40 kg/m2

Who cannot join

Subjects treated with insulin within the last three months
Subjects with any serious medical condition
Females of child bearing potential who are pregnant, breast-feeding or have the intention of becoming pregnant or not using adequate contraceptive methods
Subjects using any drug (except for OADs), which in the Investigator's opinion could interfere with the glucose level (e.g. systemic corticosteroids)

Trial locations and contacts

190 sites in 20 countries.

Country

City, postcode or hospital

190 sites in 20 countries

Germany42 sites

Novo Nordisk Investigational Site
Aschaffenburg, 63739
Novo Nordisk Investigational Site
Bad Heilbrunn, 83670
Novo Nordisk Investigational Site
Bad Kreuznach, 55545
Novo Nordisk Investigational Site
Bad Lauterberg im Harz, 37431
Novo Nordisk Investigational Site
Bad Mergentheim, 97980
Novo Nordisk Investigational Site
Bad Neuenahr-Ahrweiler, 53474
Novo Nordisk Investigational Site
Beckum, 59269
Novo Nordisk Investigational Site
Bensheim, 64625
Novo Nordisk Investigational Site
Berlin, 10115
Novo Nordisk Investigational Site
Berlin, 12203
Novo Nordisk Investigational Site
Berlin, 12687
Novo Nordisk Investigational Site
Cologne, 50858
Novo Nordisk Investigational Site
Darmstadt, 64283
Novo Nordisk Investigational Site
Diez, 65582
Novo Nordisk Investigational Site
Dormagen, 41539
Novo Nordisk Investigational Site
Dresden, 01219
Novo Nordisk Investigational Site
Dresden, 01307
Novo Nordisk Investigational Site
Flensburg, 24939
Novo Nordisk Investigational Site
Großheirath, 96269
Novo Nordisk Investigational Site
Halle, 06114
Novo Nordisk Investigational Site
Hamburg, 21073
Novo Nordisk Investigational Site
Hamburg, 22607
Novo Nordisk Investigational Site
Kutenholz-Mulsum, 27449
Novo Nordisk Investigational Site
Ludwigshafen, 67059
Novo Nordisk Investigational Site
Marburg, 35037
Novo Nordisk Investigational Site
Münster, 48145
Novo Nordisk Investigational Site
Neuwied, 56564
Novo Nordisk Investigational Site
Oberhausen, 46145
Novo Nordisk Investigational Site
Pirna, 01796
Novo Nordisk Investigational Site
Pohlheim, 35415
Novo Nordisk Investigational Site
Regensburg, 93059
Novo Nordisk Investigational Site
Rehlingen-Siersburg, 66780
Novo Nordisk Investigational Site
Saaldorf, 83416
Novo Nordisk Investigational Site
Saarbrücken, 66121
Novo Nordisk Investigational Site
Saint Ingbert, 66386
Novo Nordisk Investigational Site
Speyer, 67346
Novo Nordisk Investigational Site
Stuttgart, 70184
Novo Nordisk Investigational Site
Sulzbach-Rosenberg, 92237
Novo Nordisk Investigational Site
Tübingen, 72072
Novo Nordisk Investigational Site
Viersen, 41751
Novo Nordisk Investigational Site
Völklingen, 66333
Novo Nordisk Investigational Site
Würzburg, 97072

Other trials in Germany

Australia22 sites

Novo Nordisk Investigational Site
Adelaide, 5000
Novo Nordisk Investigational Site
Adelaide, SA 5035
Novo Nordisk Investigational Site
Auckland
Novo Nordisk Investigational Site
Bankstown, 2200
Novo Nordisk Investigational Site
Box Hill, 3128
Novo Nordisk Investigational Site
Broadmeadow, New South Wales, 2292
Novo Nordisk Investigational Site
Cairns, 4870
Novo Nordisk Investigational Site
Camperdown, 2050
Novo Nordisk Investigational Site
Christchurch, 8011
Novo Nordisk Investigational Site
Clayton, 3168
Novo Nordisk Investigational Site
Daw Park, South Australia, 5041
Novo Nordisk Investigational Site
East Ringwood, Victoria, 3135
Novo Nordisk Investigational Site
Fitzroy, 3065
Novo Nordisk Investigational Site
Fremantle, Western Australia, 6160
Novo Nordisk Investigational Site
Garran, 2605
Novo Nordisk Investigational Site
Hornsby, 2077
Novo Nordisk Investigational Site
Malvern, 3144
Novo Nordisk Investigational Site
Penrith, New South Wales, 2751
Novo Nordisk Investigational Site
Perth, 6000
Novo Nordisk Investigational Site
St Leonards, New South Wales, 2065
Novo Nordisk Investigational Site
Westmead, 2145
Novo Nordisk Investigational Site
Woodville, 5011

Other trials in Australia

Spain15 sites

Novo Nordisk Investigational Site
A Coruña, 15006
Novo Nordisk Investigational Site
Alcázar de San Juan, 13600
Novo Nordisk Investigational Site
Almería, 04001
Novo Nordisk Investigational Site
Barcelona, 08017
Novo Nordisk Investigational Site
Bilbao, 48013
Novo Nordisk Investigational Site
Cadiz, 11009
Novo Nordisk Investigational Site
Girona, 17007
Novo Nordisk Investigational Site
Granada, 18012
Novo Nordisk Investigational Site
Málaga, 29010
Novo Nordisk Investigational Site
Mérida, 06800
Novo Nordisk Investigational Site
San Cristóbal de La Laguna, 38320
Novo Nordisk Investigational Site
San Juan, 03550
Novo Nordisk Investigational Site
Santa Cruz de Tenerife, 38010
Novo Nordisk Investigational Site
Santander, 39008
Novo Nordisk Investigational Site
Seville, 41009

Other trials in Spain

Italy14 sites

Novo Nordisk Investigational Site
Bari, 70124
Novo Nordisk Investigational Site
Catania, 95126
Novo Nordisk Investigational Site
Florence, 50141
Novo Nordisk Investigational Site
Milan, 20122
Novo Nordisk Investigational Site
Milan, 20132
Novo Nordisk Investigational Site
Monza, 20052
Novo Nordisk Investigational Site
Orbassano, 10043
Novo Nordisk Investigational Site
Padova, 35128
Novo Nordisk Investigational Site
Palermo, 90127
Novo Nordisk Investigational Site
Rimini, 47900
Novo Nordisk Investigational Site
Roma, 00161
Novo Nordisk Investigational Site
Sassari, 07100
Novo Nordisk Investigational Site
Torino, 10154
Novo Nordisk Investigational Site
Verona, 37126

Other trials in Italy

United Kingdom14 sites

Novo Nordisk Investigational Site
Abergavenny, NP7 7EG
Novo Nordisk Investigational Site
Bath, BA1 2SR
Novo Nordisk Investigational Site
Bath, BA2 1NH
Novo Nordisk Investigational Site
Berkshire, RG7 3SQ
Novo Nordisk Investigational Site
Cardiff, CF23 8SQ
Novo Nordisk Investigational Site
Coventry, CV2 2DX
Novo Nordisk Investigational Site
Dundee, DD1 9SY
Novo Nordisk Investigational Site
East Horsley, KT24 6QT
Novo Nordisk Investigational Site
Frome, BA11 1EZ
Novo Nordisk Investigational Site
Llanelli, SA14 8QF
Novo Nordisk Investigational Site
Oxford, OX3 7LE
Novo Nordisk Investigational Site
Plymouth, PL6 8BQ
Novo Nordisk Investigational Site
Sheffield, S3 9DA
Novo Nordisk Investigational Site
Sunbury-on-Thames, TW16 6RH

Other trials in United Kingdom

Denmark10 sites

Novo Nordisk Investigational Site
Aalborg, 9000
Novo Nordisk Investigational Site
Århus C, 8000
Novo Nordisk Investigational Site
Copenhagen, 2400
Novo Nordisk Investigational Site
Frederiksberg, 2000
Novo Nordisk Investigational Site
Herlev, 2730
Novo Nordisk Investigational Site
Hjørring, 9800
Novo Nordisk Investigational Site
Hvidovre, 2650
Novo Nordisk Investigational Site
København S, 2300
Novo Nordisk Investigational Site
Odense, 5000
Novo Nordisk Investigational Site
Viborg

Other trials in Denmark

Norway10 sites

Novo Nordisk Investigational Site
Bekkestua, 1357
Novo Nordisk Investigational Site
Bergen, NO-5012
Novo Nordisk Investigational Site
Elverum, 2408
Novo Nordisk Investigational Site
Gjøvik, NO-2819
Novo Nordisk Investigational Site
Hamar, 2317
Novo Nordisk Investigational Site
Kongsberg, NO-3602
Novo Nordisk Investigational Site
Kongsvinger, 2212
Novo Nordisk Investigational Site
Stavanger, 4011
Novo Nordisk Investigational Site
Tromsø, 9038
Novo Nordisk Investigational Site
Trondheim, NO-7030

Other trials in Norway

Sweden8 sites

Novo Nordisk Investigational Site
Falun, 791 82
Novo Nordisk Investigational Site
Karlstad, 651 85
Novo Nordisk Investigational Site
Linköping, 581 85
Novo Nordisk Investigational Site
Lund, 221 85
Novo Nordisk Investigational Site
Malmö, 205 02
Novo Nordisk Investigational Site
Stockholm, 118 83
Novo Nordisk Investigational Site
Stockholm, 171 76
Novo Nordisk Investigational Site
Umeå, 901 85

Other trials in Sweden

Hungary7 sites

Novo Nordisk Investigational Site
Budapest, 1041
Novo Nordisk Investigational Site
Debrecen, 4043
Novo Nordisk Investigational Site
Gyula, 5700
Novo Nordisk Investigational Site
Nyíregyháza, 4400
Novo Nordisk Investigational Site
Pécs, 7631
Novo Nordisk Investigational Site
Szekszárd, 7100
Novo Nordisk Investigational Site
Zalaegerszeg, 8900

Other trials in Hungary

Slovakia7 sites

Novo Nordisk Investigational Site
Bratislava, 83 299
Novo Nordisk Investigational Site
Bratislava, 831 01
Novo Nordisk Investigational Site
Bratislava, 833 05
Novo Nordisk Investigational Site
Košice, 04-001
Novo Nordisk Investigational Site
Moldava nad Bodvou, 045 01
Novo Nordisk Investigational Site
Prešov, 080 01
Novo Nordisk Investigational Site
Trenčín, 91 101

Other trials in Slovakia

South Africa7 sites

Novo Nordisk Investigational Site
Benoni, 1500
Novo Nordisk Investigational Site
Cape Town, Western Cape, 7130
Novo Nordisk Investigational Site
Durban, KwaZulu-Natal, 4001
Novo Nordisk Investigational Site
Durban, KwaZulu-Natal, 4091
Novo Nordisk Investigational Site
Durban, KwaZulu-Natal, 4092
Novo Nordisk Investigational Site
Johannesburg, Gauteng, 1829
Novo Nordisk Investigational Site
Johannesburg, Gauteng, 27 11

Other trials in South Africa

Belgium6 sites

Novo Nordisk Investigational Site
Arlon, 6700
Novo Nordisk Investigational Site
Bonheiden, 2820
Novo Nordisk Investigational Site
Ghent, 9000
Novo Nordisk Investigational Site
Huy, 4500
Novo Nordisk Investigational Site
La Louvière, 7100
Novo Nordisk Investigational Site
Leuven, 3000

Other trials in Belgium

Russia6 sites

Novo Nordisk Investigational Site
Moscow, 117036
Novo Nordisk Investigational Site
Moscow, 119435
Novo Nordisk Investigational Site
Moscow, 127486
Novo Nordisk Investigational Site
Moscow, 129090
Novo Nordisk Investigational Site
Saint Petersburg, 194354
Novo Nordisk Investigational Site
Saint Petersburg, 198013

Other trials in Russia

India5 sites

Novo Nordisk Investigational Site
Bangalore, 560034
Novo Nordisk Investigational Site
Chennai, Tamil Nadu, 600086
Novo Nordisk Investigational Site
Hyderabad, Andhra Pradesh, 500082
Novo Nordisk Investigational Site
Kochi, Kerala, 682041
Novo Nordisk Investigational Site
Mumbai, Maharashtra, 400012

Other trials in India

Argentina4 sites

Novo Nordisk Investigational Site
Ciudad Autonoma de Bs As, C1405CWB
Novo Nordisk Investigational Site
Ciudad Autónoma de Bs As, C1426ABP
Novo Nordisk Investigational Site
Ciudad Autónoma de BsAs, C1406FWY
Novo Nordisk Investigational Site
Junín, 6000

Other trials in Argentina

Ireland4 sites

Novo Nordisk Investigational Site
Dublin, DUBLIN 15
Novo Nordisk Investigational Site
Dublin, DUBLIN 7
Novo Nordisk Investigational Site
Dublin, DUBLIN 8
Novo Nordisk Investigational Site
Waterford

Other trials in Ireland

Netherlands4 sites

Novo Nordisk Investigational Site
Apeldoorn, 7334 DZ
Novo Nordisk Investigational Site
Groningen, 9728 NT
Novo Nordisk Investigational Site
Rotterdam, 3045 PM
Novo Nordisk Investigational Site
Sliedrecht, 3361 XV

Other trials in Netherlands

Romania3 sites

Novo Nordisk Investigational Site
Cluj-Napoca, Cluj, 400006
Novo Nordisk Investigational Site
Constanța, 900591
Novo Nordisk Investigational Site
Iași, 700111

Other trials in Romania

Bulgaria1 site

Novo Nordisk Investigational Site
Sofia, 1431

Other trials in Bulgaria

Croatia1 site

Novo Nordisk Investigational Site
Zagreb, 10 000

Other trials in Croatia

About this study

Official title: Liraglutide Effect and Action in Diabetes (LEAD-2): Effect on Glycaemic Control After Once Daily Administration of Liraglutide in Combination With Metformin Versus Metformin Monotherapy Versus Metformin and Glimepiride Combination Therapy in Subjects With Type 2 Diabetes

Conditions: Diabetes, Diabetes Mellitus, Type 2
Being tested: liraglutide, metformin, 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
0.6 mg for s.c. (under the skin) injection.
metforminDrug
1.5-2.0 g tablets
glimepirideDrug
4 mg tablets
placeboDrug
Glimepiride placebo 1 mg and 2 mg tablets
placeboDrug
Liraglutide placebo 1-3 mL for s.c. (under the skin) injection
liraglutideDrug
1.2 mg for s.c. (under the skin) injection
liraglutideDrug
1.8 mg for s.c. (under the skin) injection

Study groups in NCT00318461
Study group	Role	What they receive
Lira 0.6 + Met	Experimental	Liraglutide 0.6 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day Receives: Drug: liraglutide; Drug: metformin; Drug: placebo
Lira 1.2 + Met	Experimental	Liraglutide 1.2 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day Receives: Drug: metformin; Drug: placebo; Drug: liraglutide
Lira 1.8 + Met	Experimental	Liraglutide 1.8 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day Receives: Drug: metformin; Drug: placebo; Drug: liraglutide
Met Mono	Active comparator	Metformin 1.5-2.0 g/day + liraglutide placebo + glimepiride placebo Receives: Drug: metformin; Drug: placebo
Met + Glim	Active comparator	Glimepiride 4 mg/day + metformin 1.5-2.0 g/day + liraglutide placebo Receives: Drug: metformin; Drug: glimepiride; Drug: placebo

What is being measured

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

Change in Glycosylated A1c (HbA1c) at Week 26
Percentage point change in Glycosylated A1c (HbA1c) from baseline (week 0) to 26 weeks (end of randomisation)
Measured: week 0, week 26
Change in Glycosylated A1c (HbA1c) at Week 104
Change in glycosylated A1c (HbA1c) baseline (week 0) to 104 weeks (end of randomisation)
Measured: week 0, week 104

Secondary outcomes (12)

Change in Body Weight at Week 26
Change in body weight from baseline (week 0) to 26 weeks (end of randomisation)
Measured: week 0, week 26
Change in Body Weight at Week 104
Change in body weight from baseline (week 0) to 104 weeks (end of treatment)
Measured: week 0, week 104
Change in Fasting Plasma Glucose (FPG) at Week 26
Change in fasting plasma glucose (FPG) from baseline (week 0) to 26 weeks (end of randomisation)
Measured: week 0, week 26
Change in Fasting Plasma Glucose (FPG) at Week 104
Change in Fasting plasma glucose (FPG) from baseline (week 0) to 104 weeks (end of treatment)
Measured: week 0, week 104
Change in Mean Prandial Increments of Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 26
Change in mean prandial increments of plasma glucose based on self-measured 7-point plasma glucose profiles from baseline (week 0) to 26 weeks (end of randomisation). The 7 time points for self-measurements were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner) and at bedtime.
Mean prandial increments of plasma glucose were calculated as the sum of the plasma glucose differences between values measured before and after a meal (breakfast, lunch and dinner) divided by three.
Measured: week 0, week 26
Change in Mean Prandial Increments of Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 104
Change in mean prandial increments of plasma glucose based on self-measured 7-point plasma glucose profiles from baseline (week 0) to 104 weeks (end of treatment). The 7 time points for self-measurements were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner) and at bedtime.
Mean prandial increments of plasma glucose were calculated as the sum of the plasma glucose differences between values measured before and after a meal (breakfast, lunch and dinner) divided by three.
Measured: week 0, week 104
Change in Mean Post Prandial Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 26
Change in mean post prandial plasma glucose from baseline (Week 0) to 26 weeks (end of randomisation). The 7 time points for self-measurements were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner) and at bedtime. Mean post prandial plasma glucose were calculated as the sum of the post pradial plasma glucose values divided by three.
Measured: week 0, week 26
Change in Mean Post Prandial Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 104
Change in mean post prandial plasma glucose from baseline (Week 0) to 104 weeks (end of treatment) The 7 time points for self-measurements were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner) and at bedtime. Mean post prandial plasma glucose were calculated as the sum of the post pradial plasma glucose values divided by three.
Measured: week 0, week 104
Change in Beta-cell Function at Week 26
Change in beta cell function from baseline (week 0) to 16 weeks (end of treatment). Beta-cell function was derived from fasting plasma glucose (FPG) and fasting insulin concentrations using the homeostasic model assessment (HOMA) method which uses the assumption that normal-weight normal subjects aged under 35 years have a 100% beta-cell function (HOMA-B).
Beta-cell function: HOMA-B (%) = 20∙fasting insulin[uU/mL] divided by (FPG mmol/L]-3.5).
Measured: week 0, week 26
Change in Beta-cell Function at Week 104
Change in beta cell function from baseline (week 0) to 16 weeks (end of treatment). Beta-cell function was derived from fasting plasma glucose (FPG) and fasting insulin concentrations using the homeostasic model assessment (HOMA) method which uses the assumption that normal-weight normal subjects aged under 35 years have a 100% beta-cell function (HOMA-B).
Beta-cell function: HOMA-B (%) = 20∙fasting insulin[uU/mL] divided by (FPG mmol/L]-3.5).
Measured: week 0, week 104
Hypoglycaemic Episodes at Week 26
Total number of hypoglycaemic episodes occuring after baseline (week 0) until week 26 (end of randomisation). 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 3.1 mmol/L. Symptoms only if subject was able to treat her/himself and with no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L.
Measured: weeks 0-26
Hypoglycaemic Episodes at Week 104
Total number of hypoglycaemic episodes occuring after baseline (week 0) until 104 weeks (end of treatment). 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 3.1 mmol/L. Symptoms only if subject was able to treat her/himself and with no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L.
Measured: weeks 0-104

Timeline

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

May 2006Nov 2008

First posted26 Apr 2006 (estimated)
Study startMay 2006
Primary completionMay 2007
Study completionNov 2008

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 (18)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: 1,091 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00318461
Sponsor's protocol ID: NN2211-1572
Acronym: LEAD-2
Status last verified: Jan 2017
First submitted: 25 Apr 2006
Last updated: 7 Mar 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Nauck M, Frid A, Hermansen K, Shah NS, Tankova T, Mitha IH, Zdravkovic M, During M, Matthews DR; LEAD-2 Study Group. Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study. Diabetes Care. 2009 Jan;32(1):84-90. doi: 10.2337/dc08-1355. Epub 2008 Oct 17.
PubMed 18931095
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
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.
PubMed 19491535
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
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
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
Davies MJ, Chubb BD, Smith IC, Valentine WJ. Cost-utility analysis of liraglutide compared with sulphonylurea or sitagliptin, all as add-on to metformin monotherapy in Type 2 diabetes mellitus. Diabet Med. 2012 Mar;29(3):313-20. doi: 10.1111/j.1464-5491.2011.03429.x.
PubMed 21883438
Nauck M, Frid A, Hermansen K, Thomsen AB, During M, Shah N, Tankova T, Mitha I, Matthews DR. Long-term efficacy and safety comparison of liraglutide, glimepiride and placebo, all in combination with metformin in type 2 diabetes: 2-year results from the LEAD-2 study. Diabetes Obes Metab. 2013 Mar;15(3):204-12. doi: 10.1111/dom.12012. Epub 2012 Oct 11.
PubMed 22985213
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

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

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All Diabetes trials

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-2): Effect on Glycaemic Control After Once Daily Administration of Liraglutide in Combination With Metformin Versus Metformin Monotherapy Versus Metformin and Glimepiride Combination Therapy in Subjects With Type 2 Diabetes
ClinicalTrials.gov ID: NCT00318461
Acronym / sponsor ID: LEAD-2 / NN2211-1572
Conditions: Diabetes, Diabetes Mellitus, Type 2
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 1,091 participants (actual)
Lead sponsor: Novo Nordisk A/SIndustry (pharma, biotech, devices)
Study start: May 2006
Primary completion: May 2007 (actual)
Study completion: Nov 2008 (actual)
First posted: 26 Apr 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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 5

Arm	Type	Receives
Lira 0.6 + Met	Experimental	Drug: liraglutide, Drug: metformin, Drug: placeboLiraglutide 0.6 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day
Lira 1.2 + Met	Experimental	Drug: metformin, Drug: placebo, Drug: liraglutideLiraglutide 1.2 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day
Lira 1.8 + Met	Experimental	Drug: metformin, Drug: placebo, Drug: liraglutideLiraglutide 1.8 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day
Met Mono	Active comparator	Drug: metformin, Drug: placeboMetformin 1.5-2.0 g/day + liraglutide placebo + glimepiride placebo
Met + Glim	Active comparator	Drug: metformin, Drug: glimepiride, Drug: placeboGlimepiride 4 mg/day + metformin 1.5-2.0 g/day + liraglutide placebo

Who may qualify

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

Key inclusion criteria (3 listed)

Subjects diagnosed with type 2 diabetes and treated with oral anti-diabetic drugs (OADs) 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 40 kg/m2

Key exclusion criteria (4 listed)

Subjects treated with insulin within the last three months
Subjects with any serious medical condition
Females of child bearing potential who are pregnant, breast-feeding or have the intention of becoming pregnant or not using adequate contraceptive methods
Subjects using any drug (except for OADs), which in the Investigator's opinion could interfere with the glucose level (e.g. systemic corticosteroids)

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
liraglutide0.6 mg for s.c. (under the skin) injection.	Drug	Lira 0.6 + Met
metformin1.5-2.0 g tablets	Drug	Lira 0.6 + Met, Lira 1.2 + Met, Lira 1.8 + Met, Met + Glim, Met Mono
glimepiride4 mg tablets	Drug	Met + Glim
placeboGlimepiride placebo 1 mg and 2 mg tablets	Drug	Lira 0.6 + Met, Lira 1.2 + Met, Lira 1.8 + Met, Met Mono
placeboLiraglutide placebo 1-3 mL for s.c. (under the skin) injection	Drug	Met + Glim, Met Mono
liraglutide1.2 mg for s.c. (under the skin) injection	Drug	Lira 1.2 + Met
liraglutide1.8 mg for s.c. (under the skin) injection	Drug	Lira 1.8 + Met

Primary outcome

Change in Glycosylated A1c (HbA1c) at Week 26
Time frame: week 0, week 26
Percentage point change in Glycosylated A1c (HbA1c) from baseline (week 0) to 26 weeks (end of randomisation)
Change in Glycosylated A1c (HbA1c) at Week 104
Time frame: week 0, week 104
Change in glycosylated A1c (HbA1c) baseline (week 0) to 104 weeks (end of randomisation)

12 secondary outcomes

Change in Body Weight at Week 26
Time frame: week 0, week 26
Change in Body Weight at Week 104
Time frame: week 0, week 104
Change in Fasting Plasma Glucose (FPG) at Week 26
Time frame: week 0, week 26
Change in Fasting Plasma Glucose (FPG) at Week 104
Time frame: week 0, week 104
Change in Mean Prandial Increments of Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 26
Time frame: week 0, week 26
Change in Mean Prandial Increments of Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 104
Time frame: week 0, week 104
Change in Mean Post Prandial Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 26
Time frame: week 0, week 26
Change in Mean Post Prandial Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 104
Time frame: week 0, week 104
Change in Beta-cell Function at Week 26
Time frame: week 0, week 26
Change in Beta-cell Function at Week 104
Time frame: week 0, week 104
Hypoglycaemic Episodes at Week 26
Time frame: weeks 0-26
Hypoglycaemic Episodes at Week 104
Time frame: weeks 0-104

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 0.6 + Met	242	208
Lira 1.2 + Met	241	197
Lira 1.8 + Met	242	191
Met Mono	122	74
Met + Glim	244	210

Primary outcome: Change in Glycosylated A1c (HbA1c) at Week 26

Time frame: week 0, week 26. Least squares mean (Standard Error). Unit: Percentage point of total HbA1c

Measure	Lira 0.6 + Met n = 239	Lira 1.2 + Met n = 232	Lira 1.8 + Met n = 236	Met Mono n = 120	Met + Glim n = 234
Value	-0.69 (0.07)	-0.97 (0.07)	-1.00 (0.07)	0.09 (0.09)	-0.98 (0.07)

Lira 1.8 + Met vs Met Mono: Estimated treatment difference, LS Mean: -1.09 (95% CI -1.30 to -0.88), p <0.0001, ANCOVA
Lira 1.8 + Met vs Met + Glim: Estimated treatment difference, LS Mean: -0.02 (95% CI -0.19 to 0.15), p <0.0001, ANCOVA
Lira 1.2 + Met vs Met Mono: Estimated treatment difference, LS Mean: -1.06 (95% CI -1.27 to -0.85), p <0.0001, 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 A1c (HbA1c) at Week 104

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

Measure	Lira 0.6 + Met n = 239	Lira 1.2 + Met n = 231	Lira 1.8 + Met n = 235	Met Mono n = 120	Met + Glim n = 234
Value	-0.36 (0.08)	-0.56 (0.08)	-0.58 (0.08)	0.25 (0.10)	-0.50 (0.08)

Lira 1.8 + Met vs Met Mono: Estimated treatment difference, LS Mean: -0.83 (95% CI -1.07 to -0.59), p <0.0001, ANCOVA
Lira 1.8 + Met vs Met + Glim: Estimated treatment difference, LS Mean: -0.08 (95% CI -0.28 to 0.12), p <0.0001, ANCOVA
Lira 1.2 + Met vs Met Mono: Estimated treatment difference, LS Mean: -0.81 (95% CI -1.05 to -0.57), p <0.0001, 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.

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were collected over 24 months of treatment. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Lira 0.6 + Met	36 of 242 (14.9%)	132 of 242 (54.5%)	Not reported
Lira 1.2 + Met	25 of 240 (10.4%)	144 of 240 (60%)	Not reported
Lira 1.8 + Met	16 of 242 (6.6%)	158 of 242 (65.3%)	Not reported
Met Mono	9 of 121 (7.4%)	44 of 121 (36.4%)	Not reported
Met + Glim	24 of 242 (9.9%)	128 of 242 (52.9%)	Not reported

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 18931095Nauck M, Frid A, Hermansen K, Shah NS, Tankova T, Mitha IH, Zdravkovic M, During M, Matthews DR; LEAD-2 Study Group. Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study. Diabetes Care. 2009 Jan;32(1):84-90. doi: 10.2337/dc08-1355. Epub 2008 Oct 17.
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 19491535Nauck 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.
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 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 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 21883438Davies MJ, Chubb BD, Smith IC, Valentine WJ. Cost-utility analysis of liraglutide compared with sulphonylurea or sitagliptin, all as add-on to metformin monotherapy in Type 2 diabetes mellitus. Diabet Med. 2012 Mar;29(3):313-20. doi: 10.1111/j.1464-5491.2011.03429.x.
Results publication: PubMed 22985213Nauck M, Frid A, Hermansen K, Thomsen AB, During M, Shah N, Tankova T, Mitha I, Matthews DR. Long-term efficacy and safety comparison of liraglutide, glimepiride and placebo, all in combination with metformin in type 2 diabetes: 2-year results from the LEAD-2 study. Diabetes Obes Metab. 2013 Mar;15(3):204-12. doi: 10.1111/dom.12012. Epub 2012 Oct 11.
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

190 sites in 20 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing liraglutide, metformin and glimepiride in people with Diabetes and Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 190 sites in 20 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 3 inclusion and 4 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: finished, 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 190 sites in Germany, Australia, Spain, Italy, United Kingdom and 15 more countries. 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 A1c (HbA1c) at Week 26 (time frame: week 0, week 26). The study lists 2 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 NCT00318461, which also lists 18 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.