Table 3.

Summary of liraglutide studies: the pivotal studies were termed the LEAD series. The dosages of liraglutide were 0.6 mg, 1.2 mg, and 1.8 mg.

Study	Intervening medication	Population, duration	Mean % change in HbA1c	Mean change in body weight	Adverse events (AEs)
Marre et al. [2009] LEAD 1	Liraglutide 0.6 mg Liraglutide 1.2 mg Liraglutide 1.8 mg Rosiglitazone 4 mg Placebo	Glimepiride treated (n = 1041) 26 weeks	Liraglutide 0.6 mg: –0.60% (p < 0.05 versus glimepiride) Liraglutide 1.2 mg: –1.08% (p < 0.001 versus placebo) Liraglutide 1.8 mg: –1.13% (p < 0.001 versus placebo) Rosiglitazone: –0.44% Placebo: +0.23%	Liraglutide 1.8 mg: –0.2 kg Liraglutide 1.2 mg: +0.3 kg Rosiglitazone: +2.1 kg Placebo: –0.1 kg (p < 0.0001)	Liraglutide 1.2 mg: nausea (10.2%), vomiting (4.4%), diarrhea (7.9%), serious AEs (4%) Liraglutide 1.8 mg: serious AEs (5%) Rosiglitazone: serious AEs (3%) Placebo: nausea (1.8%), serious AEs (3%)
Nauck et al. [2009] LEAD 2	Liraglutide 0.6 mg Liraglutide 1.2 mg Liraglutide 1.8 mg Glimepiride 4 mg Placebo	Metformin treated (n = 1091) 26 weeks	Liraglutide 0.6 mg: –0.69% (p < 0.001 versus placebo) Liraglutide 1.2 mg: –0.97% (p < 0.001 versus placebo) Liraglutide 1.8 mg: –1.00% Glimepiride: –0.98% (p < 0.001 versus placebo) Placebo: +0.09 (1.0)	Body weight decreased in all liraglutide groups (1.8–2.8 kg) compared with an increase in the glimepiride group (1.0 kg; p < 0.0001)	Liraglutide groups: nausea (35–44%), vomiting (5–7%), diarrhea (10–15%) Placebo and glimepiride groups: nausea (17%), vomiting (1%), diarrhea (4%)
Garber et al. [2009] LEAD 3	Liraglutide 1.2 mg Liraglutide 1.8 mg Glimepiride 8 mg	Diet and exercise treated (n = 746) 52 weeks	Liraglutide 1.2 mg: –0.84% (p < 0.01 versus diet) Liraglutide 1.8 mg: –1.14% (p < 0.001 versus placebo) Glimepiride: –0.51%		Liraglutide 1.2 mg: nausea (27.5%), vomiting (9.3%), diarrhea (15.5%) Liraglutide 1.8 mg: nausea (29.3%), vomiting (12.4%), diarrhea (18.7%) Glimepiride: nausea (8.5%; p < 0.001), vomiting (3.6%, p < 0.001), diarrhea (8.9%)
Zinman et al. [2009] LEAD 4	Liraglutide 1.2 mg Liraglutide 1.8 mg Placebo	Metformin and rosiglitazone n = 533 26 weeks	Liraglutide 1.2 mg: –1.5% (p < 0.001 versus placebo) Liraglutide 1.8 mg: –1.5% (p < 0.001 versus placebo) Placebo: –0.5%	Dose-dependent weight loss occurred with 1.2 and 1.8 mg liraglutide (1.0 ± 0.3 and 2.0 ± 0.3 kg, respectively) (p < 0.0001) compared with weight gain with placebo (0.6 ± 0.3 kg)	Gastrointestinal AEs (nausea, vomiting, diarrhea): Liraglutide 1.2 mg: 45% Liraglutide 1.8 mg: 56% Placebo: 19%
Russell-Jones [2009] LEAD 5	Liraglutide 1.8 mg Insulin glargine Placebo	Metformin and glimepiride n = 581 26 weeks	Liraglutide 1.8 mg: –1.33% (1.4) (p < 0.001 versus placebo) Glargine: –1.09% Placebo: –0.24%	Greater weight loss with liraglutide versus placebo (difference –1.39 kg, 95% CI 2.10–0.69; p = 0.0001), and versus glargine (difference –3.43 kg, 95% CI 4.00–2.86; p < 0.0001)	Liraglutide: nausea (13.9%), vomiting (6.5%), diarrhea (10%), Glargine: nausea (1.3%), vomiting (0.4%), diarrhea (1.3%) Placebo: nausea (3.9%), vomiting (3.5%), diarrhea (5.3%)
LEAD 6	Liraglutide 1.8 mg Exenatide 10 μg twice daily	Metformin or sulfonylurea (n = 464) 26 weeks	Liraglutide 1.8 mg: –1.12% (p < 0.001 versus placebo) Exenatide: –0.79%	Both drugs promoted similar weight losses (liraglutide –3.24 kg versus exenatide –2.87 kg)	Liraglutide: diarrhea (12.3%), dyspepsia (8.9%), nausea (25.5%), vomiting (6.0%) Exenatide: diarrhea (12.1%), dyspepsia (4.7%), nausea (28.0%), vomiting (9.9%)

The Liraglutide studies were grouped in a series named “LEAD”. Each study is listed by first author. The comparative treatments in each study are listed along with the baseline therapy in the population studied and the duration of the study. The mean change in hemoglobin A1c (HbA1c), mean weight loss, and adverse events, chiefly gastrointestinal, are listed for the comparative treatments. HbA1c, hemoglobin A1c.