Table 1.

Weight loss as a secondary endpoint in phase III trials of liraglutide for the treatment of type 2 diabetes.

Trial name	Study population	Study groups	Primary outcome measure	Duration	Weight change with 0.6 mg	1.2 mg	1.8 mg	Statistical significance of weight loss
LEAD-1 (SU)	n = 1041 T2DM OHGs for >3 months HbA1c 7.0–11.0% BMI < 45 Age 18–80 No insulin in previous 3 months	OHGs discontinued and glimepiride (2–4 mg daily) introduced.Study arms: (1) liraglutide (0.6 or 1.2 or 1.8 mg daily) + rosiglitazone placebo; (2) liraglutide placebo + rosiglitazone 4 mg daily; (3) liraglutide placebo + rosiglitazone placebo	Change in HbA1c from baseline at 26 weeks	26 weeks	+0.7 kg	+0.3 kg	−0.2 kg	Nonsignificant compared with double placebo
LEAD-2 (Met)	n = 1091 T2DM OHGs for >3 months HbA1c 7.0–11.0% BMI < 45 Age 18–80 No insulin in previous 3 months	OHGs discontinued and metformin (1000 mg BD) introduced.Study arms: (1) liraglutide (0.6 or 1.2 or 1.8 mg daily) + glimepiride placebo; (2) liraglutide placebo + glimepiride 4 mg daily; (3) liraglutide placebo + glimepiride placebo	Change in HbA1c from baseline at 26 weeks	26 weeks	−1.8 kg	−2.6 kg	−2.8 kg	Versus placebop < 0.01 for 1.2 and 1.8 mgVersus glimepiride 4 mg p < 0.0001 for 0.6, 1.2 and 1.8 mg
LEAD-3 (Mono)	n = 746 T2DM Managed with diet and exercise or up to half the maximum dose of OHG monotherapy HbA1c 7.0–11.0% BMI < 45 Age 18–80 No insulin in previous 3 months	OHG monotherapy discontinued.Study arms: (1) liraglutide (1.2 or 1.8 mg daily) + glimepiride placebo; (2) liraglutide placebo + glimepiride 8 mg daily	Change in HbA1c from baseline at 52 weeks	52 weeks	N/A	−2.0 kg	−2.4 kg	Versus glimepiride 8 mg p = 0.0001 for 1.2 and 1.8 mg
LEAD-4 (Met+TZD)	n = 821 T2DM HbA1c 7.0–11.0% BMI < 45 Age 18–80 On one or more OHGs No insulin in previous 3 months	OHG therapy discontinued.	Change in HbA1c from baseline at 26 weeks	26 weeks	N/A	−1.0 kg	−2.0 kg	Versus placebo p < 0.0001 for 1.2 and 1.8 mg
		Metformin (1000 mg BD) and rosiglitazone (8 mg OD) introduced.
		Study arms: (1) liraglutide 1.2 mg; (2) liraglutide 1.8 mg; (3) liraglutide placebo.
LEAD-5 (Met + SU)	n = 581 T2DM HbA1c 7.0–10.0% BMI < 45 Age 18–80 On one or more OHGs No insulin in previous 3 months	OHG therapy discontinued.	Change in HbA1c at 26 weeks	26 weeks	N/A	N/A	−1.8 kg	Versus placebop = 0.0001 Versus lantusp < 0.0001
		Metformin (1000 mg BD) and glimepiride 4 mg OD) introduced.
		Study arms: (1) liraglutide 1.8 mg; (2) liraglutide placebo; (3) Lantus (patient-titrated by protocol – open label)
LEAD-6 (versus exanatide BD head-to-head)	n = 464 T2DM HbA1c 7.0–11.0% BMI < 45 Age 18–80 On metformin, sulfonylurea or both No previous insulin or GLP-1 agonist	Previous therapy continued.	Change in HbA1c at 26 weeks	26 weeks	N/A	N/A	−3.2 kg	Nonsignificant
		Study arms: (1) liraglutide 1.8 mg OD; (2) Exenatide (Byetta) 10 µg BD
		Open label
DURATION-6 (versus exenatide once weekly head-to-head)	n = 911 T2DM HbA1c 7.1–11.0% BMI < 45 Age 18 or older Metformin ± sulfonylurea or pioglitazone	Previous therapy continued.Study arms: (1) liraglutide 1.8 mg OD; (2) exenatide (Bydureon) 2 mg once weekly Open Label	Change in HbA1c at 26 weeks	26 weeks	N/A	N/A	−3.6 kg	Liraglutide superior to exenatide, p = 0.0005

OHG, Oral hypoglycaemic; T2DM, type 2 diabetes mellitus; BMI, body mass index; OD, once daily; BD, twice daily; N/A, not available.