Trial · Interventional

CompletedPhase 3Results postedRegistry data

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

Short name LEAD-2

NCTNCT00318461Other idNN2211-1572

Open at ClinicalTrials.govAsk about this trial

Overview

Status: Completed
Phase: Phase 3
Enrollment: 1,091 participants (actual)
Sponsor: Novo Nordisk A/S · Industry
Design: Randomized · Double masking
Countries: 20 countries
Argentina, Australia, Belgium, Bulgaria, Croatia, Denmark, Germany, Hungary, India, Ireland, Italy, Netherlands, Norway, Romania, Russia, Slovakia, South Africa, Spain, Sweden, United Kingdom
Start: May 2006
Primary completion: May 2007
Completion: Nov 2008
First posted: 26 Apr 2006 (estimated)
Last update posted: 7 Mar 2017
Conditions: Diabetes · Diabetes Mellitus, Type 2

Timeline

1 trial · 1 completed · 1 with posted results

Completed
Ongoing
Not yet recruiting
Stopped
Estimated dates (est.)
Results posted

2006200720082009

Ph 3
LEAD-2
NCT00318461
May 2006 to Nov 2008

Registry summary

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

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. Two trial periods: A 6 month (26 weeks) randomised, double-blinded period followed by an 18 months open-label extension, in total 2 years (104 weeks).

Interventions

liraglutideDrug
metforminDrug
glimepirideDrug
placeboDrug
placeboDrug
liraglutideDrug
liraglutideDrug

Arms5

Experimental
Lira 0.6 + Met
Liraglutide 0.6 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day
Experimental
Lira 1.2 + Met
Liraglutide 1.2 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day
Experimental
Lira 1.8 + Met
Liraglutide 1.8 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day
Active comparator
Met Mono
Metformin 1.5-2.0 g/day + liraglutide placebo + glimepiride placebo
Active comparator
Met + Glim
Glimepiride 4 mg/day + metformin 1.5-2.0 g/day + liraglutide placebo

Primary outcomes2

Outcomes the sponsor listed as primary.

Change in Glycosylated A1c (HbA1c) at Week 26
Time frame · week 0, week 26
Registry description
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
Registry description
Change in glycosylated A1c (HbA1c) baseline (week 0) to 104 weeks (end of randomisation)

Secondary outcomes(12)

Change in Body Weight at Week 26
Time frame · week 0, week 26
Registry description
Change in body weight from baseline (week 0) to 26 weeks (end of randomisation)
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 treatment)
Change in Fasting Plasma Glucose (FPG) at Week 26
Time frame · week 0, week 26
Registry description
Change in fasting plasma glucose (FPG) from baseline (week 0) to 26 weeks (end of randomisation)
Change in Fasting Plasma Glucose (FPG) 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 treatment)
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
Registry description
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.
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
Registry description
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.
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
Registry description
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.
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
Registry description
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.
Change in Beta-cell Function at Week 26
Time frame · week 0, week 26
Registry description
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).
Change in Beta-cell Function at Week 104
Time frame · week 0, week 104
Registry description
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).
Hypoglycaemic Episodes at Week 26
Time frame · weeks 0-26
Registry description
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.
Hypoglycaemic Episodes at Week 104
Time frame · weeks 0-104
Registry description
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.

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 26

Change in Glycosylated A1c (HbA1c) at Week 26

Group	Value (Percentage point of total HbA1c)	Spread
Lira 0.6 + Met	-0.69	0.07
Lira 1.2 + Met	-0.97	0.07
Lira 1.8 + Met	-1.00	0.07
Met Mono	0.09	0.09
Met + Glim	-0.98	0.07

Primary outcomeLeast squares mean· week 0, week 104

Change in Glycosylated A1c (HbA1c) at Week 104

Group	Value (percentage of total haemoglobin)	Spread
Lira 0.6 + Met	-0.36	0.08
Lira 1.2 + Met	-0.56	0.08
Lira 1.8 + Met	-0.58	0.08
Met Mono	0.25	0.10
Met + Glim	-0.50	0.08

Secondary and other outcome results(6)

Secondary outcomeLeast squares mean· week 0, week 26

Change in Body Weight at Week 26

Group	Value (kg)	Spread
Lira 0.6 + Met	-1.78	0.23
Lira 1.2 + Met	-2.58	0.24
Lira 1.8 + Met	-2.79	0.23
Met Mono	-1.51	0.31
Met + Glim	0.95	0.23

Secondary outcomeLeast squares mean· week 0, week 104

Change in Body Weight at Week 104

Group	Value (kg)	Spread
Lira 0.6 + Met	-2.07	0.28
Lira 1.2 + Met	-3.03	0.29
Lira 1.8 + Met	-2.91	0.28
Met Mono	-1.80	0.38
Met + Glim	0.70	0.29

Secondary outcomeLeast squares mean· week 0, week 26

Change in Fasting Plasma Glucose (FPG) at Week 26

Group	Value (mmol/L)	Spread
Lira 0.6 + Met	-1.13	0.15
Lira 1.2 + Met	-1.63	0.16
Lira 1.8 + Met	-1.68	0.15
Met Mono	0.40	0.21
Met + Glim	-1.31	0.16

Secondary outcomeLeast squares mean· week 0, week 104

Change in Fasting Plasma Glucose (FPG) at Week 104

Group	Value (mmol/L)	Spread
Lira 0.6 + Met	-0.80	0.17
Lira 1.2 + Met	-1.20	0.18
Lira 1.8 + Met	-1.18	0.17
Met Mono	0.75	0.23
Met + Glim	-0.64	0.17

Secondary outcomeLeast squares mean· week 0, week 26

Change in Mean Prandial Increments of Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 26

Group	Value (mmol/l)	Spread
Lira 0.6 + Met	-0.23	0.12
Lira 1.2 + Met	-0.40	0.13
Lira 1.8 + Met	-0.56	0.12
Met Mono	-0.44	0.18
Met + Glim	-0.44	0.12

Secondary outcomeLeast squares mean· week 0, week 104

Change in Mean Prandial Increments of Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 104

Group	Value (mmol/L)	Spread
Lira 0.6 + Met	-0.27	0.12
Lira 1.2 + Met	-0.56	0.13
Lira 1.8 + Met	-0.44	0.13
Met Mono	-0.20	0.18
Met + Glim	-0.29	0.13

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
Group	Deaths	Serious events	Other events
Lira 0.6 + MetLiraglutide 0.6 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 0.6 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	–	36 / 242	132 / 242
Lira 1.2 + MetLiraglutide 1.2 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.2 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	–	25 / 240	144 / 240
Lira 1.8 + MetLiraglutide 1.8 mg/day + glimepiride placebo + metformin 1.5-2.0 g/day, weeks 0-26 (double-blinded period) and open-label liraglutide 1.8 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	–	16 / 242	158 / 242
Met MonoMetformin 1.5-2.0 g/day + liraglutide placebo + glimepiride placebo, weeks 0-26 (double-blinded period) and open-label metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	–	9 / 121	44 / 121
Met + GlimGlimepiride 4 mg/day + metformin 1.5-2.0 g/day + liraglutide placebo, weeks 0-26 (double-blinded period) and open-label glimepiride 4 mg/day + metformin 1.5-2.0 g/day in the extension period (weeks 26-104)	–	24 / 242	128 / 242

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

Studies18

Studies that cite this trial.

Studies with results

13 studies on this page

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 page See results (8)

Indexing hint: Observational study · 2013

12 results

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.

Nauck et al. 2013Diabetes, obesity & metabolismcited by 122

PMID 22985213DOI 10.1111/dom.12012PUB-22985213

Full text at the publisher12 results

Publisher page See results (12)

Indexing hint: Observational study · 2012

12 results

Cost-utility analysis of liraglutide compared with sulphonylurea or sitagliptin, all as add-on to metformin monotherapy in Type 2 diabetes mellitus.

Davies et al. 2012Diabetic medicine : a journal of the British Diabetic Associationcited by 37

PMID 21883438PMC3378710DOI 10.1111/j.1464-5491.2011.03429.xPUB-21883438

CC BY12 results

Download PDF See results (12)

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 page See results (3)

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 page See 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 link See 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 page See 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 page See 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 page See results (4)

Indexing hint: Randomized controlled trial · 2009

8 results

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.

Nauck et al. 2009Diabetes carecited by 849

PMID 18931095PMC2606836DOI 10.2337/dc08-1355PUB-18931095

Free to read · publisher termsCC BY-NC-ND8 results

Read at source See results (8)

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 PDF See results (10)

Indexing hint: Randomized controlled trial · 2009

6 results

Adding liraglutide to oral antidiabetic drug monotherapy: efficacy and weight benefits.

Nauck et al. 2009Postgraduate medicinecited by 25

PMID 19491535DOI 10.3810/pgm.2009.05.1997PUB-19491535

Full text at the publisher6 results

Publisher page See results (6)

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 link See 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 link Read 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: * 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 Exclusion Criteria: * 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)

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