Phase 3 · Liraglutide

LEAD-2 trial results

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

Change in Glycosylated A1c (HbA1c) at Week 26 (Percentage point of total HbA1c), week 0, week 26. Lira 0.6 + Met: -0.69; Lira 1.2 + Met: -0.97; Lira 1.8 + Met: -1.00; Met Mono: 0.09; Met + Glim: -0.98.

Participants: 1,091
Status: completed
Completed: 2008-11
Sponsor: Novo Nordisk A/S

As posted on ClinicalTrials.gov (NCT00318461), updated at source Mar 7, 2017. Read again whenever the registry updates it. Registry figures can differ from a published paper, which may use another analysis.

Primary outcome

What LEAD-2 measured first

Change in Glycosylated A1c (HbA1c) at Week 26Percentage point of total HbA1c · week 0, week 26 · least squares mean

Lira 0.6 + Metn=239	Lira 1.2 + Metn=232	Lira 1.8 + Metn=236	Met Monon=120	Met + Glimn=234
-0.69(0.07)	-0.97(0.07)	-1.00(0.07)	0.09(0.09)	-0.98(0.07)

Change in Glycosylated A1c (HbA1c) at Week 104percentage of total haemoglobin · week 0, week 104 · least squares mean

Lira 0.6 + Metn=239	Lira 1.2 + Metn=231	Lira 1.8 + Metn=235	Met Monon=120	Met + Glimn=234
-0.36(0.08)	-0.56(0.08)	-0.58(0.08)	0.25(0.10)	-0.50(0.08)

Side effects by arm

Side effects in LEAD-2

Percent of participants affected, Adverse events were collected over 24 months of treatment. The most common events the registry lists.

Event	Lira 0.6 + Met	Lira 1.2 + Met	Lira 1.8 + Met	Met Mono	Met + Glim
Any serious event	14.9%	10.4%	6.6%	7.4%	9.9%
Nausea	12.4%	17.5%	21.5%	4.1%	4.1%
Nasopharyngitis	17.8%	15%	14.9%	9.9%	20.2%
Diarrhoea	12.8%	11.3%	16.5%	4.1%	5.8%
Headache	10.7%	14.2%	14.5%	6.6%	13.2%
Vomiting	7.9%	7.5%	9.9%	0%	0.4%
Dyspepsia	5%	2.5%	9.1%	0.8%	2.9%
Back pain	6.6%	6.3%	7%	4.1%	8.7%
Arthralgia	5.8%	2.1%	3.7%	4.1%	7.9%
Influenza	5.8%	6.3%	7%	4.1%	7.4%
Upper respiratory tract infection	4.5%	5.8%	6.2%	3.3%	5%
Bronchitis	4.1%	5.4%	5%	2.5%	6.2%
Anorexia	2.5%	4.2%	6.2%	0.8%	0.4%
Decreased appetite	1.7%	5.8%	4.1%	0%	0%
Gastritis	4.1%	3.3%	5.4%	0.8%	1.7%
Toothache	2.5%	5.4%	2.9%	5%	1.2%
Hypertension	4.5%	5.4%	4.5%	1.7%	5%
Cough	3.3%	2.5%	0.8%	1.7%	5.4%

Secondary outcomes

What else it measured

Change in Body Weight at Week 26kg · week 0, week 26 · least squares mean

Lira 0.6 + Metn=242	Lira 1.2 + Metn=236	Lira 1.8 + Metn=241	Met Monon=121	Met + Glimn=237
-1.78(0.23)	-2.58(0.24)	-2.79(0.23)	-1.51(0.31)	0.95(0.23)

Change in Body Weight at Week 104kg · week 0, week 104 · least squares mean

Lira 0.6 + Metn=242	Lira 1.2 + Metn=236	Lira 1.8 + Metn=241	Met Monon=121	Met + Glimn=237
-2.07(0.28)	-3.03(0.29)	-2.91(0.28)	-1.80(0.38)	0.70(0.29)

Change in Fasting Plasma Glucose (FPG) at Week 26mmol/L · week 0, week 26 · least squares mean

Lira 0.6 + Metn=238	Lira 1.2 + Metn=234	Lira 1.8 + Metn=235	Met Monon=116	Met + Glimn=234
-1.13(0.15)	-1.63(0.16)	-1.68(0.15)	0.40(0.21)	-1.31(0.16)

Change in Fasting Plasma Glucose (FPG) at Week 104mmol/L · week 0, week 104 · least squares mean

Lira 0.6 + Metn=238	Lira 1.2 + Metn=233	Lira 1.8 + Metn=234	Met Monon=116	Met + Glimn=234
-0.80(0.17)	-1.20(0.18)	-1.18(0.17)	0.75(0.23)	-0.64(0.17)

Change in Mean Prandial Increments of Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 26mmol/l · week 0, week 26 · least squares mean

Lira 0.6 + Metn=214	Lira 1.2 + Metn=207	Lira 1.8 + Metn=205	Met Monon=90	Met + Glimn=213
-0.23(0.12)	-0.40(0.13)	-0.56(0.12)	-0.44(0.18)	-0.44(0.12)

Change in Mean Prandial Increments of Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 104mmol/L · week 0, week 104 · least squares mean

Lira 0.6 + Metn=218	Lira 1.2 + Metn=208	Lira 1.8 + Metn=206	Met Monon=90	Met + Glimn=215
-0.27(0.12)	-0.56(0.13)	-0.44(0.13)	-0.20(0.18)	-0.29(0.13)

Change in Mean Post Prandial Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 26mmol/L · week 0, week 26 · least squares mean

Lira 0.6 + Metn=214	Lira 1.2 + Metn=207	Lira 1.8 + Metn=205	Met Monon=90	Met + Glimn=214
-1.68(0.16)	-2.33(0.17)	-2.57(0.16)	-0.62(0.24)	-2.46(0.16)

Change in Mean Post Prandial Plasma Glucose Based on Self-measured 7-point Plasma Glucose Profiles at Week 104mmol/L · week 0, week 104 · least squares mean

Lira 0.6 + Metn=218	Lira 1.2 + Metn=208	Lira 1.8 + Metn=206	Met Monon=90	Met + Glimn=216
-1.59(0.18)	-2.22(0.18)	-2.10(0.18)	-0.43(0.26)	-1.80(0.18)

Change in Beta-cell Function at Week 26percentage point (%point) · week 0, week 26 · least squares mean

Lira 0.6 + Metn=229	Lira 1.2 + Metn=224	Lira 1.8 + Metn=224	Met Monon=109	Met + Glimn=226
20.45(5.19)	20.33(5.34)	26.12(5.20)	-1.63(7.19)	24.68(5.25)

Change in Beta-cell Function at Week 104percentage point (%point) · week 0, week 104 · least squares mean

Lira 0.6 + Metn=230	Lira 1.2 + Metn=224	Lira 1.8 + Metn=224	Met Monon=110	Met + Glimn=226
64.48(24.93)	27.30(25.70)	17.81(25.03)	-7.89(34.47)	11.25(25.27)

Hypoglycaemic Episodes at Week 26episodes · weeks 0-26 · number

Measure	Lira 0.6 + Metn=242	Lira 1.2 + Metn=240	Lira 1.8 + Metn=242	Met Monon=121	Met + Glimn=242
Major	0	0	0	0	0
Minor	15	3	9	6	136
Symptoms only	17	7	22	10	175

Hypoglycaemic Episodes at Week 104episodes · weeks 0-104 · number

Measure	Lira 0.6 + Metn=242	Lira 1.2 + Metn=240	Lira 1.8 + Metn=242	Met Monon=121	Met + Glimn=242
All	52	51	49	18	524
Major	0	1	0	0	0
Minor	23	26	22	6	284
Symptoms only	29	24	27	12	240

The trial

How LEAD-2 was run

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).

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

Who could join the trial

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)

Published papers

Papers from LEAD-2

Trial averages do not predict what one person will experience. Results are shown as the registry posts them, without interpretation.

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