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Trial · Interventional

TerminatedPhase 3Results postedRegistry data

To Evaluate the Effect of Liraglutide Versus Glimepiride (Amaryl®) on Haemoglobin A1c

Short name LEAD-3

NCTNCT00294723 (opens ClinicalTrials.gov in a new tab)Other idNN2211-1573
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Terminated
Phase
Phase 3
Enrollment
746 participants (actual)
Sponsor
Novo Nordisk A/S · Industry
Design
Randomized · Double masking
Countries
3 countries

United States, Mexico, Puerto Rico

Start
Feb 2006
Primary completion
Nov 2008
Completion
Nov 2008
First posted
22 Feb 2006 (estimated)
Last update posted
7 Mar 2017
Conditions
Diabetes · Diabetes Mellitus, Type 2

Timeline

1 trial · 1 stopped early · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2006200720082009
  1. Ph 3

    LEAD-3

    NCT00294723

    Feb 2006 to Nov 2008

    Terminated

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

This trial is conducted in North America (the United States of America (USA) and Mexico). The trial is designed to evaluate the effects of treatment with liraglutide versus glimepiride in subjects with type 2 diabetes. The trial is a 52-week randomised, double-blind trial period plus a 52-week open-label extension (week 104) followed by an additional 156-week continued open-label extension. The total duration of the treatment period is planned to be 260 weeks (5 years).

Interventions

  • liraglutideDrug
  • glimepirideDrug
  • liraglutideDrug
  • placeboDrug
  • placeboDrug
  • placeboDrug

Arms4

  • Experimental

    Lira 1.8

    Liraglutide 1.8 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.8 mg once daily in the extension periods (weeks 52-195).

  • Experimental

    Lira 1.2

    Liraglutide 1.2 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.2 mg once daily in the extension periods (weeks 52-195).

  • Active comparator

    Glimepiride - 1

    Glimepiride 8 mg once daily + liraglutide placebo 200 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension periods (weeks 52-195).

  • Active comparator

    Glimepiride - 2

    Glimepiride 8 mg once daily + liraglutide placebo 300 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension periods (weeks 52-195).

Primary outcomes3

Outcomes the sponsor listed as primary.

  1. Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 52

    Time frame · week 0, week 52

    Registry description

    Percentage point change in Glycosylated Haemoglobin A1c (HbA1c) from baseline (week 0) to 52 weeks (end of double-blind period)

  2. Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 104

    Time frame · week 0, week 104

    Registry description

    Percentage point change in Glycosylated Haemoglobin A1c (HbA1c) from baseline (week 0) to 104 weeks (end of 52-week extension)

  3. Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 156

    Time frame · week 0, week 156

    Registry description

    Percentage point change in Glycosylated Haemoglobin A1c (HbA1c) from baseline (week 0) to 156 weeks

Secondary outcomes(14)

  1. Change in Body Weight at Week 52

    Time frame · week 0, week 52

    Registry description

    Change in body weight from baseline (week 0) to 52 weeks (end of double-blind period)

  2. Change in Body Weight at Week 104

    Time frame · week 0, week 104

    Registry description

    Change in body weight from baseline (week 0) to 104 weeks (end of 52-week extension)

  3. Change in Body Weight at Week 156

    Time frame · week 0, week 156

    Registry description

    Change in body weight from baseline (week 0) to 156 weeks

  4. Change in Fasting Plasma Glucose at Week 52

    Time frame · week 0, week 52

    Registry description

    Change in fasting plasma glucose (FPG) from baseline (week 0) to 52 weeks (end of double-blind period)

  5. Change in Fasting Plasma Glucose at Week 104

    Time frame · week 0, week 104

    Registry description

    Change in fasting plasma glucose (FPG) from baseline (week 0) to 104 weeks (end of 52-week extension)

  6. Change in Fasting Plasma Glucose at Week 156

    Time frame · week 0, week 156

    Registry description

    Change in fasting plasma glucose (FPG) from baseline (week 0) to 156 weeks

  7. Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 52

    Time frame · week 0, week 52

    Registry description

    Change in mean postprandial glucose (PPG) based on self-measured 8-point plasma glucose profiles from baseline (week 0) to 52 weeks (end of double-blind period). The 8 time points for self-measurements of plasma glucose were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min.

  8. Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 104

    Time frame · week 0, week 104

    Registry description

    Change in mean postprandial glucose (PPG) based on self-measured 8-point plasma glucose profiles from baseline (week 0) to 104 weeks (end of 52-week extension). The 8 time points for self-measurements of plasma glucose were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min.

  9. Change in Mean Postprandial Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 156

    Time frame · week 0, week 156

    Registry description

    Change in mean postprandial glucose (PPG) based on self-measured 8-point plasma glucose profiles from baseline (week 0) to 156 weeks. The 8 time points for self-measurements of plasma glucose were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min.

  10. Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 52

    Time frame · week 0, week 52

    Registry description

    Change in mean prandial increments of plasma glucose from baseline (week 0) to 52 weeks (end of double-blind period). The 8 time points for self-measured 8-point plasma glucose profiles were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min. Mean prandial increments of plasma glucose were calculated as the sum of the plasma glucose differences between post- and pre-meal values (for breakfast, lunch and dinner) divided by three.

  11. Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 104

    Time frame · week 0, week 104

    Registry description

    Change in mean prandial increments of plasma glucose from baseline (week 0) to 104 weeks (end of 52-week extension). The 8 time points for self-measured 8-point plasma glucose profiles were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min. Mean prandial increments of plasma glucose were calculated as the sum of the plasma glucose differences between post- and pre-meal values (for breakfast, lunch and dinner) divided by three.

  12. Change in Prandial Increments of Plasma Glucose Based on Self-measured 8-point Plasma Glucose Profiles at Week 156

    Time frame · week 0, week 156

    Registry description

    Change in mean prandial increments (incr.) of plasma glucose from baseline (week 0) to 156 weeks. The 8 time points for self-measured 8-point plasma glucose profiles were: before each meal (breakfast, lunch and dinner), at 90 min after start of each meal (breakfast, lunch and dinner), at bedtime, and at 3:00 AM ± 30 min. Mean prandial increments of plasma glucose were calculated as the sum of the plasma glucose differences between post- and pre-meal values (for breakfast, lunch and dinner) divided by three.

  13. Hypoglycaemic Episodes

    Time frame · weeks 0-104

    Registry description

    Total number of hypoglycaemic episodes occuring from baseline (week 0) to 104 weeks (end of the 52-week extension). 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 56 mg/dL. Symptoms only if subject was able to treat her/himself and with no plasma glucose measurement or plasma glucose higher than or equal to 56 mg/dL.

  14. Hypoglycaemic Episodes

    Time frame · weeks 104-195

    Registry description

    Total number of hypoglycaemic episodes occuring from week 104 to end of trial (week 195). 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 56 mg/dL. Symptoms only if subject was able to treat her/himself and with no plasma glucose measurement or plasma glucose higher than or equal to 56 mg/dL.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeLeast squares mean· week 0, week 52

Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 52

GroupValue (percentage point of total HbA1c)Spread
Lira 1.8-1.140.08
Lira 1.2-0.840.08
Glimepiride-0.510.08
Primary outcomeLeast squares mean· week 0, week 104

Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 104

GroupValue (percentage point of total HbA1c)Spread
Lira 1.8-0.880.09
Lira 1.2-0.590.09
Glimepiride-0.280.09
Secondary and other outcome results(6)
Secondary outcomeLeast squares mean· week 0, week 52

Change in Body Weight at Week 52

GroupValue (kg)Spread
Lira 1.8-2.450.28
Lira 1.2-2.050.28
Glimepiride1.120.27
Secondary outcomeLeast squares mean· week 0, week 104

Change in Body Weight at Week 104

GroupValue (kg)Spread
Lira 1.8-2.700.32
Lira 1.2-1.890.31
Glimepiride0.950.30
Secondary outcomeLeast squares mean· week 0, week 156

Change in Body Weight at Week 156

GroupValue (kg)Spread
Lira 1.8-2.430.32
Lira 1.2-1.680.32
Glimepiride1.050.31
Secondary outcomeLeast squares mean· week 0, week 52

Change in Fasting Plasma Glucose at Week 52

GroupValue (mg/dL)Spread
Lira 1.8-25.573.50
Lira 1.2-15.213.50
Glimepiride-5.293.33
Secondary outcomeLeast squares mean· week 0, week 104

Change in Fasting Plasma Glucose at Week 104

GroupValue (mg/dL)Spread
Lira 1.8-15.823.85
Lira 1.2-9.363.85
Glimepiride1.973.66
Secondary outcomeLeast squares mean· week 0, week 156

Change in Fasting Plasma Glucose at Week 156

GroupValue (mg/dL)Spread
Lira 1.8-12.063.8
Lira 1.2-5.453.8
Glimepiride4.573.62

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Lira 1.8 (Weeks 0-104)Liraglutide 1.8 mg once daily + glimepiride placebo 8 mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.8 mg once daily in the extension period (weeks 52-104)–22 / 246183 / 246
Lira 1.2 (Weeks 0-104)Liraglutide 1.2 mg once daily + glimepiride placebo 8mg once daily, weeks 0-52 (double-blinded period) and open-label liraglutide 1.2 mg once daily in the extension period (weeks 52-104)–23 / 251181 / 251
Glimepiride (Weeks 0-104)Glimepiride 8 mg once daily + liraglutide placebo 200 mcl or liraglutide placebo 300 mcl, weeks 0-52 (double-blinded period) and open-label glimepiride 8 mg once daily in the extension period (weeks 52-104)–20 / 248148 / 248
Lira 1.8 (Weeks 104-195)Open-label liraglutide 1.8 mg once daily in the additional extension period (weeks 104-195)–5 / 6240 / 62
Lira 1.2 (Weeks 104-195)Open-label liraglutide 1.2 mg once daily in the additional extension period (weeks 104-195)–1 / 5337 / 53
Glimepiride (Weeks 104-195)Open-label glimepiride 8 mg once daily in the additional extension period (weeks 104-195)–2 / 2813 / 28

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies19

Studies that cite this trial.

Studies with results

13 studies on this page

Indexing hint: Randomized controlled trial · 2016

1 result

COMPARISON OF THE LONG-TERM EFFECTS OF LIRAGLUTIDE AND GLIMEPIRIDE MONOTHERAPY ON BONE MINERAL DENSITY IN PATIENTS WITH TYPE 2 DIABETES.

Gilbert et al. 2016Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologistscited by 68

PMID 26574791DOI 10.4158/ep15758.orPUB-26574791

Full text at the publisher1 result
Publisher pageSee results (1)

Indexing hint: Meta-analysis (pooled) · 2016

6 results

Efficacy and safety of liraglutide, a once-daily human glucagon-like peptide-1 analogue, in Latino/Hispanic patients with type 2 diabetes: post hoc analysis of data from four phase III trials.

Davidson et al. 2016Diabetes, obesity & metabolismcited by 12

PMID 26936426DOI 10.1111/dom.12653PUB-26936426

Rights unknown6 results
Source linkSee results (6)

Indexing hint: Randomized controlled trial · 2013

8 results

Weight change with liraglutide and comparator therapies: an analysis of seven phase 3 trials from the liraglutide diabetes development programme.

Niswender et al. 2013Diabetes, obesity & metabolismcited by 75

PMID 22862847DOI 10.1111/j.1463-1326.2012.01673.xPUB-22862847

Full text at the publisher8 results
Publisher pageSee results (8)

Indexing hint: Meta-analysis (pooled) · 2012

3 results

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.

Zinman et al. 2012Diabetes, obesity & metabolismcited by 81

PMID 21883806DOI 10.1111/j.1463-1326.2011.01493.xPUB-21883806

Full text at the publisher3 results
Publisher pageSee results (3)

Indexing hint: Randomized controlled trial · 2012

Dosing rationale for liraglutide in type 2 diabetes mellitus: a pharmacometric assessment.

Ingwersen et al. 2012Journal of clinical pharmacologycited by 32

PMID 22174428DOI 10.1177/0091270011430504PUB-22174428

Full text at the publisher
Publisher page

Indexing hint: Meta-analysis (pooled) · 2012

3 results

A meta-analysis of serious adverse events reported with exenatide and liraglutide: acute pancreatitis and cancer.

Alves et al. 2012Diabetes research and clinical practicecited by 142

PMID 23010561DOI 10.1016/j.diabres.2012.09.008PUB-23010561

Full text at the publisher3 results
Publisher pageSee results (3)

Indexing hint: Randomized controlled trial · 2011

3 results

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.

Hegedüs et al. 2011The Journal of clinical endocrinology and metabolismcited by 150

PMID 21209033DOI 10.1210/jc.2010-2318PUB-21209033

Rights unknown3 results
Source linkSee results (3)

Indexing hint: Clinical trial · 2011

6 results

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.

Buse et al. 2011The Journal of clinical endocrinology and metabolismcited by 116

PMID 21450987DOI 10.1210/jc.2010-2822PUB-21450987

Full text at the publisher6 results
Publisher pageSee results (6)

Indexing hint: Observational study · 2011

8 results

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.

Bode et al. 2011The American journal of geriatric pharmacotherapycited by 43

PMID 22055210DOI 10.1016/j.amjopharm.2011.09.007PUB-22055210

Full text at the publisher8 results
Publisher pageSee results (8)

Indexing hint: Meta-analysis (pooled) · 2011

4 results

Efficacy of antihyperglycemic therapies and the influence of baseline hemoglobin A(1C): a meta-analysis of the liraglutide development program.

Henry et al. 2011Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologistscited by 42

PMID 22193143DOI 10.4158/ep.17.6.906PUB-22193143

Full text at the publisher4 results
Publisher pageSee results (4)

Indexing hint: Randomized controlled trial · 2010

11 results

Patient-reported outcomes following treatment with the human GLP-1 analogue liraglutide or glimepiride in monotherapy: results from a randomized controlled trial in patients with type 2 diabetes.

Bode et al. 2010Diabetes, obesity & metabolismcited by 62

PMID 20590735PMC2901519DOI 10.1111/j.1463-1326.2010.01196.xPUB-20590735

CC BY11 results
Download PDFSee results (11)

Indexing hint: Randomized controlled trial · 2009

4 results

Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial.

Garber et al. 2009Lancet (London, England)cited by 798

PMID 18819705DOI 10.1016/s0140-6736(08)61246-5PUB-18819705

Full text at the publisher4 results
Publisher pageSee results (4)

Indexing hint: Clinical trial · 2009

10 results

Long-term outcomes in patients with type 2 diabetes receiving glimepiride combined with liraglutide or rosiglitazone.

Sullivan et al. 2009Cardiovascular diabetologycited by 18

PMID 19245711PMC2667489DOI 10.1186/1475-2840-8-12PUB-19245711

CC BY10 results
Download PDFSee results (10)

Indexing hint: Randomized controlled trial · 2009

11 results

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.

Jendle et al. 2009Diabetes, obesity & metabolismcited by 236

PMID 19930006DOI 10.1111/j.1463-1326.2009.01158.xPUB-19930006

Rights unknown11 results
Source linkSee results (11)

More studies

5 studies on this page

Indexing hint: Meta-analysis (pooled) · 2015

Corrected

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.

Jensen et al. 2015Diabetes carecited by 45

PMID 25504028DOI 10.2337/dc13-1210PUB-25504028

Rights unknown
Source linkRead the notice

PubMed tag: none · 2014

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.

Fonseca et al. 2014Journal of diabetes and its complicationscited by 79

PMID 24561125PMC4231710DOI 10.1016/j.jdiacomp.2014.01.009PUB-24561125

Free to read · publisher termsCC BY-NC-ND
Read at source

PubMed tag: none · 2013

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%.

King et al. 2013Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologistscited by 14

PMID 23186975DOI 10.4158/ep12232.orPUB-23186975

Full text at the publisher
Publisher page

Indexing hint: Review · 2009

Insights from the Liraglutide Clinical Development Program--the Liraglutide Effect and Action in Diabetes (LEAD) studies.

McGill et al. 2009Postgraduate medicinecited by 32

PMID 19491536DOI 10.3810/pgm.2009.05.1998PUB-19491536

Full text at the publisher
Publisher page

Indexing hint: Review · 2009

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.

Blonde et al. 2009Diabetes, obesity & metabolismcited by 165

PMID 19878259DOI 10.1111/j.1463-1326.2009.01075.xPUB-19878259

Full text at the publisher
Publisher page

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years up to 80 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: * Type 2 diabetes * TTreatment with diet/exercise or with not more than half maximal dose of oral anti-diabetic drugs alone for at least 2 months * Diet/exercise treated subjects with HbA1c between 7.0% and 11%, inclusive * OAD (oral anti-diabetic drug) treated subjects with HbA1c between 7.0% and 10%, inclusive * Body Mass Index (BMI) less than or equal to 45 kg/m\^2 Exclusion Criteria: * Treatment with insulin for the last 3 months, except short-term treatment for intercurrent illness * Treatment with any drug that could interfere with the glucose level (besides use of a single anti-diabetic compound) * Any serious medical condition

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