LEAD-3

TerminatedPhase 3Results posted

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

Liraglutide Effect and Action in Diabetes (LEAD-3): Effect on Glycemic Control of Liraglutide Versus Glimepiride in Type 2 Diabetes

Lead sponsor

Novo Nordisk A/S

Asset

Liraglutide

Subcutaneous · GLP-1 agonist

Listed sites

117

Recruiting sites

—

Enrollment

746

actual

Study population

Type 2 diabetes

Key I/E criteria

•BMI ≤45•HbA1c 7-11%

Primary endpoint

•HbA1c, change

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT00294723

Org study IDNN2211-1573

Timeline

Milestones

Study first posted2006-02-22estimated

Results first posted2010-03-12estimated

Last update posted2017-03-07actual

Study start2006-02 (month precision)

Primary completion2008-11actual (month precision)

Study completion2008-11actual (month precision)

Assets

Investigational agents

Liraglutide

Study populations

Who this study enrolls

Type 2 diabetes

Eligibility

Who can enroll

Minimum age18 Years

Maximum age80 Years

SexAll

Healthy volunteersNot accepted

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

Endpoints (34)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Glycemic / diabetes

Weight & body composition

Safety / tolerability / PK

Weight & body composition

6 endpoints

Secondary/registry result

Change in Body Weight at Week 52

Time frame:week 0, week 52

Body weight, absolute change (kg)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), kg	95% CI
Lira 1.8	-2.45	—
Lira 1.2	-2.05	—
Glimepiride	1.12	—

Estimated treatment difference, LS Mean-3.5895% CI-4.28 – -2.87p<.0001ANCOVA

Estimated treatment difference, LS Mean-3.1795% CI-3.87 – -2.47p<.0001ANCOVA

Estimated treatment difference, LS Mean-0.4195% CI-1.11 – 0.30p0.2584ANCOVA

Secondary/registry result

Change in Body Weight at Week 104

Time frame:week 0, week 104

Body weight, absolute change (kg)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), kg	95% CI
Lira 1.8	-2.70	—
Lira 1.2	-1.89	—
Glimepiride	0.95	—

Estimated treatment difference, LS Mean-3.6595% CI-4.44 – -2.86p<.0001ANCOVA

Estimated treatment difference, LS Mean-2.8495% CI-3.63 – -2.06p<.0001ANCOVA

Estimated treatment difference, LS Mean-0.8095% CI-1.59 – -0.01p0.0462ANCOVA

Secondary/registry result

Change in Body Weight at Week 156

Time frame:week 0, week 156

Body weight, absolute change (kg)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), kg	95% CI
Lira 1.8	-2.43	—
Lira 1.2	-1.68	—
Glimepiride	1.05	—

Estimated treatment difference, LS Mean-3.4895% CI-4.28 – -2.68p<0.0001ANCOVA

Estimated treatment difference, LS Mean-2.7295% CI-3.52 – -1.93p<0.0001ANCOVA

Estimated treatment difference, LS Mean-0.7595% CI-1.55 – 0.05p0.0642ANCOVA

Secondary/protocol endpoint

Change in Body Weight at Week 52

Time frame:week 0, week 52

Body weight, absolute change (kg)

change from baseline, improvement

Secondary/protocol endpoint

Change in Body Weight at Week 104

Time frame:week 0, week 104

Body weight, absolute change (kg)

change from baseline, improvement

Secondary/protocol endpoint

Change in Body Weight at Week 156

Time frame:week 0, week 156

Body weight, absolute change (kg)

change from baseline, improvement

Glycemic / diabetes

24 endpoints

Primary/registry result

Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 52

Time frame:week 0, week 52

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Posted result

Group	Value (least_squares_mean), percentage point of total HbA1c	95% CI
Lira 1.8	-1.14	—
Lira 1.2	-0.84	—
Glimepiride	-0.51	—

Estimated treatment difference, LS Mean-0.6295% CI-0.83 – -0.42p<0.0001ANCOVA

Estimated treatment difference, LS Mean-0.3395% CI-0.53 – -0.13p0.0014ANCOVA

Estimated treatment difference, LS Mean-0.2995% CI-0.50 – -0.09p0.0046ANCOVA

Primary/registry result

Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 104

Time frame:week 0, week 104

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Posted result

Group	Value (least_squares_mean), percentage point of total HbA1c	95% CI
Lira 1.8	-0.88	—
Lira 1.2	-0.59	—
Glimepiride	-0.28	—

Estimated treatment difference, LS Mean-0.6095% CI-0.83 – -0.38p<.0001ANCOVA

Estimated treatment difference, LS Mean-0.3195% CI-0.54 – -0.08p0.0076ANCOVA

Estimated treatment difference, LS Mean-0.2995% CI-0.52 – -0.06p0.0129ANCOVA

Primary/registry result

Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 156

Time frame:week 0, week 156

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Posted result

Group	Value (least_squares_mean), percentage point of total HbA1c	95% CI
Lira 1.8	-0.71	—
Lira 1.2	-0.44	—
Glimepiride	-0.16	—

Estimated treatment difference, LS Mean-0.5595% CI-0.77 – -0.34p<0.0001ANCOVA

Estimated treatment difference, LS Mean-0.2895% CI-0.49 – -0.06p0.0122ANCOVA

Estimated treatment difference, LS Mean-0.2895% CI-0.49 – -0.06p0.0123ANCOVA

Primary/protocol endpoint

Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 52

Time frame:week 0, week 52

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Primary/protocol endpoint

Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 104

Time frame:week 0, week 104

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Primary/protocol endpoint

Change in Glycosylated Haemoglobin A1c (HbA1c) at Week 156

Time frame:week 0, week 156

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/registry result

Change in Fasting Plasma Glucose at Week 52

Time frame:week 0, week 52

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Posted result

Group	Value (least_squares_mean), mg/dL	95% CI
Lira 1.8	-25.57	—
Lira 1.2	-15.21	—
Glimepiride	-5.29	—

Estimated treatment difference, LS Mean-20.2895% CI-29.09 – -11.46p<.0001ANCOVA

Estimated treatment difference, LS Mean-9.9295% CI-18.70 – -1.12p0.0270ANCOVA

Estimated treatment difference, LS Mean-10.3695% CI-19.24 – -1.48p0.0223ANCOVA

Secondary/registry result

Change in Fasting Plasma Glucose at Week 104

Time frame:week 0, week 104

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Posted result

Group	Value (least_squares_mean), mg/dL	95% CI
Lira 1.8	-15.82	—
Lira 1.2	-9.36	—
Glimepiride	1.97	—

Estimated treatment difference, LS Mean-17.7995% CI-27.48 – -8.09p0.0003ANCOVA

Estimated treatment difference, LS Mean-11.3395% CI-20.99 – -1.66p0.0217ANCOVA

Estimated treatment difference, LS Mean-6.4695% CI-16.23 – 3.30p0.1942ANCOVA

Secondary/registry result

Change in Fasting Plasma Glucose at Week 156

Time frame:week 0, week 156

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Posted result

Group	Value (least_squares_mean), mg/dL	95% CI
Lira 1.8	-12.06	—
Lira 1.2	-5.45	—
Glimepiride	4.57	—

Estimated treatment difference, LS Mean-16.6395% CI-26.19 – -7.06p0.0007ANCOVA

Estimated treatment difference, LS Mean-10.0295% CI-19.56 – -0.49p0.0395ANCOVA

Estimated treatment difference, LS Mean-6.6095% CI-16.24 – 3.03p0.1789ANCOVA

Secondary/registry result

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

Time frame:week 0, week 52

Postprandial glucose

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), mg/dL	95% CI
Lira 1.8	-37.4	—
Lira 1.2	-30.8	—
Glimepiride	-24.5	—

Estimated treatment difference, LS Mean-12.995% CI-21.6 – -4.2p0.0038ANCOVA

Estimated treatment difference, LS Mean-6.395% CI-15.0 – 2.5p0.1616ANCOVA

Estimated treatment difference, LS Mean-6.695% CI-15.3 – 2.0p0.1319ANCOVA

Secondary/registry result

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

Time frame:week 0, week 104

Postprandial glucose

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), mg/dL	95% CI
Lira 1.8	-37.15	—
Lira 1.2	-27.34	—
Glimepiride	-24.85	—

Estimated treatment difference, LS Mean-12.3095% CI-21.71 – -2.89p0.0105ANCOVA

Estimated treatment difference, LS Mean-2.4995% CI-11.95 – 6.98p0.6060ANCOVA

Estimated treatment difference, LS Mean-9.8195% CI-19.14 – -0.49p0.0392ANCOVA

Secondary/registry result

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

Time frame:week 0, week 156

Postprandial glucose

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), mg/dL	95% CI
Lira 1.8	-34.83	—
Lira 1.2	-25.68	—
Glimepiride	-23.84	—

Estimated treatment difference, LS Mean-10.9895% CI-20.42 – -1.54p0.0227ANCOVA

Estimated treatment difference, LS Mean-1.8395% CI-11.33 – 7.66p0.7047ANCOVA

Estimated treatment difference, LS Mean-9.1595% CI-18.51 – 0.21p0.0553ANCOVA

Secondary/registry result

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

Postprandial glucose

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), mg/dL	95% CI
Lira 1.8	-9.6	—
Lira 1.2	-8.4	—
Glimepiride	-5.6	—

Estimated treatment difference, LS Mean-4.095% CI-9.4 – 1.3p0.1396ANCOVA

Estimated treatment difference, LS Mean-2.995% CI-8.3 – 2.5p0.2968ANCOVA

Estimated treatment difference, LS Mean-1.295% CI-6.5 – 4.1p0.6639ANCOVA

Secondary/registry result

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

Postprandial glucose

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), mg/dL	95% CI
Lira 1.8	-11.76	—
Lira 1.2	-8.28	—
Glimepiride	-7.95	—

Estimated treatment difference, LS Mean-3.8195% CI-9.28 – 1.66p0.1720ANCOVA

Estimated treatment difference, LS Mean-0.3395% CI-5.82 – 5.16p0.9060ANCOVA

Estimated treatment difference, LS Mean-3.4895% CI-8.91 – 1.95p0.2089ANCOVA

Secondary/registry result

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

Postprandial glucose

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), mg/dL	95% CI
Lira 1.8	-11.01	—
Lira 1.2	-7.53	—
Glimepiride	-7.97	—

Estimated treatment difference, LS Mean-3.0495% CI-8.51 – 2.42p0.2749ANCOVA

Estimated treatment difference, LS Mean0.4395% CI-5.05 – 5.92p0.8765ANCOVA

Estimated treatment difference, LS Mean-3.4895% CI-8.90 – 1.95p0.2088ANCOVA

Secondary/protocol endpoint

Change in Fasting Plasma Glucose at Week 52

Time frame:week 0, week 52

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Secondary/protocol endpoint

Change in Fasting Plasma Glucose at Week 104

Time frame:week 0, week 104

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Secondary/protocol endpoint

Change in Fasting Plasma Glucose at Week 156

Time frame:week 0, week 156

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Secondary/protocol endpoint

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

Time frame:week 0, week 52

Postprandial glucose

change from baseline, improvement

Secondary/protocol endpoint

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

Time frame:week 0, week 104

Postprandial glucose

change from baseline, improvement

Secondary/protocol endpoint

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

Time frame:week 0, week 156

Postprandial glucose

change from baseline, improvement

Secondary/protocol endpoint

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

Postprandial glucose

change from baseline, improvement

Secondary/protocol endpoint

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

Postprandial glucose

change from baseline, improvement

Secondary/protocol endpoint

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

Postprandial glucose

change from baseline, improvement

Safety / tolerability / PK

4 endpoints

Secondary/registry result

Hypoglycaemic Episodes

Time frame:weeks 0-104

Documented hypoglycemia

event count, event

Posted result

Group	Value (number), episodes	95% CI
Lira 1.8Major	1	—
Minor	71	—
Symptoms only	87	—
Lira 1.2Major	0	—
Minor	68	—
Symptoms only	133	—
GlimepirideMajor	0	—
Minor	533	—
Symptoms only	405	—

Secondary/registry result

Hypoglycaemic Episodes

Time frame:weeks 104-195

Documented hypoglycemia

event count, event

Posted result

Group	Value (number), episodes	95% CI
Lira 1.8Major	0	—
Minor	13	—
Symptoms only	3	—
Lira 1.2Major	0	—
Minor	3	—
Symptoms only	1	—
GlimepirideMajor	1	—
Minor	34	—
Symptoms only	4	—

Secondary/protocol endpoint

Hypoglycaemic Episodes

Time frame:weeks 0-104

Documented hypoglycemia

event count, event

Secondary/protocol endpoint

Hypoglycaemic Episodes

Time frame:weeks 104-195

Documented hypoglycemia

event count, event

Publications (19)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

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.
Diabetes, obesity & metabolism2016 Jul (month)PMID26936426doi:10.1111/dom.12653via CT.gov reference
COMPARISON OF THE LONG-TERM EFFECTS OF LIRAGLUTIDE AND GLIMEPIRIDE MONOTHERAPY ON BONE MINERAL DENSITY IN PATIENTS WITH TYPE 2 DIABETES.
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists2016 Apr (month)PMID26574791doi:10.4158/EP15758.ORvia CT.gov reference + pubmed nct search
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 care2015 Jun (month)PMID25504028doi:10.2337/dc13-1210via CT.gov reference
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.
Journal of diabetes and its complications2014 May-Jun (year)PMID24561125doi:10.1016/j.jdiacomp.2014.01.009via clinicaltrials gov reference derived + pubmed nct search
Weight change with liraglutide and comparator therapies: an analysis of seven phase 3 trials from the liraglutide diabetes development programme.
Diabetes, obesity & metabolism2013 Jan (month)PMID22862847doi:10.1111/j.1463-1326.2012.01673.xvia CT.gov reference
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%.
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists2013 Jan-Feb (year)PMID23186975doi:10.4158/EP12232.ORvia CT.gov reference
Dosing rationale for liraglutide in type 2 diabetes mellitus: a pharmacometric assessment.
Journal of clinical pharmacology2012 Dec (month)PMID22174428doi:10.1177/0091270011430504via CT.gov reference
A meta-analysis of serious adverse events reported with exenatide and liraglutide: acute pancreatitis and cancer.
Diabetes research and clinical practice2012 Nov (month)PMID23010561doi:10.1016/j.diabres.2012.09.008via CT.gov reference
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, obesity & metabolism2012 Jan (month)PMID21883806doi:10.1111/j.1463-1326.2011.01493.xvia CT.gov reference
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.
The American journal of geriatric pharmacotherapy2011 Dec (month)PMID22055210doi:10.1016/j.amjopharm.2011.09.007via CT.gov reference
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.
The Journal of clinical endocrinology and metabolism2011 Jun (month)PMID21450987doi:10.1210/jc.2010-2822via CT.gov reference + pubmed nct search
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.
The Journal of clinical endocrinology and metabolism2011 Mar (month)PMID21209033doi:10.1210/jc.2010-2318via clinicaltrials gov reference derived + pubmed nct search
Efficacy of antihyperglycemic therapies and the influence of baseline hemoglobin A(1C): a meta-analysis of the liraglutide development program.
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists2011 Nov-Dec (year)PMID22193143doi:10.4158/ep.17.6.906via CT.gov reference
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.
Diabetes, obesity & metabolism2010 Jul (month)PMID20590735doi:10.1111/j.1463-1326.2010.01196.xvia CT.gov reference
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, obesity & metabolism2009 Dec (month)PMID19878259doi:10.1111/j.1463-1326.2009.01075.xvia CT.gov reference
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, obesity & metabolism2009 Dec (month)PMID19930006doi:10.1111/j.1463-1326.2009.01158.xvia CT.gov reference
Insights from the Liraglutide Clinical Development Program--the Liraglutide Effect and Action in Diabetes (LEAD) studies.
Postgraduate medicine2009 May (month)PMID19491536doi:10.3810/pgm.2009.05.1998via CT.gov reference
Long-term outcomes in patients with type 2 diabetes receiving glimepiride combined with liraglutide or rosiglitazone.
Cardiovascular diabetology2009 Feb 26PMID19245711doi:10.1186/1475-2840-8-12via CT.gov reference + pubmed nct search
Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial.
Lancet (London, England)2009 Feb 7PMID18819705doi:10.1016/S0140-6736(08)61246-5via CT.gov reference + pubmed nct search

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 1, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.