AIM: The effect on body composition of liraglutide, a once-daily human 
glucagon-like peptide-1 analogue, as monotherapy or added to metformin was 
examined in patients with type 2 diabetes (T2D).
METHODS: These were randomized, double-blind, parallel-group trials of 26 
[Liraglutide Effect and Action in Diabetes-2 (LEAD-2)] and 52 weeks (LEAD-3). 
Patients with T2D, aged 18-80 years, body mass index (BMI) < or =40 kg/m(2) 
(LEAD-2), < or =45 kg/m(2) (LEAD-3) and HbA1c 7.0-11.0% were included. Patients 
were randomized to liraglutide 1.8, 1.2 or 0.6 mg/day, placebo or glimepiride 4 
mg/day, all combined with metformin 1.5-2 g/day in LEAD-2 and to liraglutide 
1.8, 1.2 or glimepiride 8 mg/day in LEAD-3. LEAD-2/3: total lean body tissue, 
fat tissue and fat percentage were measured. LEAD-2: adipose tissue area and 
hepatic steatosis were assessed.
RESULTS: LEAD-2: fat percentage with liraglutide 1.2 and 1.8 mg/metformin was 
significantly reduced vs. glimepiride/metformin (p < 0.05) but not vs. placebo. 
Visceral and subcutaneous adipose tissue areas were reduced from baseline in all 
liraglutide/metformin arms. Except with liraglutide 0.6 mg/metformin, reductions 
were significantly different vs. changes seen with glimepiride (p < 0.05) but 
not with placebo. Liver-to-spleen attenuation ratio increased with liraglutide 
1.8 mg/metformin possibly indicating reduced hepatic steatosis. LEAD-3: 
reductions in fat mass and fat percentage with liraglutide monotherapy were 
significantly different vs. increases with glimepiride (p < 0.01).
CONCLUSION: Liraglutide (monotherapy or added to metformin) significantly 
reduced fat mass and fat percentage vs. glimepiride in patients with T2D.