Objective: Determine the effects of liraglutide with diet and exercise, on cardiometabolic risk factors in obese adults.
Design and intervention: Multicentre placebo-controlled double blind trial, with randomisation 2:1 to liraglutide 3.0 mg or placebo, stratified by pre-diabetes status. All participants received a structured diet (500 kcal/day deficit) and exercise program.
Participants: 3731 non-diabetic individuals (age >18 years, BMI ≥27 kg/m2 with comorbidities, or ≥30 kg/m2) were randomised to either liraglutide 3.0 mg (n=2487) or placebo (n=1244).
Outcome measures (Week 56): Primary – weight loss; Secondary – waist circumference and other cardiometabolic risk factors. Data are estimated treatment differences (ETD) or relative difference (lipids) from model-adjusted data (ANCOVA/logistic regression) using the full analysis set (n=3662), last observation carried forward.
Results: Baseline characteristics: 45.1 years, 78.5% female, weight 106.2 kg, BMI 38.3 kg/m2, 61.2% pre-diabetes). Liraglutide 3.0 mg compared with placebo induced: greater decreases in weight (8.0% vs. 2.6%, ETD: -5.4% [95%CI: ‑5.8; -5.0]; p<0.0001), waist (‑4.2 [-4.7; -3.7] cm) and diastolic/systolic blood pressure (-2.8/-0.9 [‑3.6; -2.1/-1.4; -0.4] mmHg) (all p<0.001); increase in pulse (2.4 [1.9; 3.0] beats/min, p<0.0001); decreases in glucose (-0.38 [-0.42; -0.35] mmol/L), HbA1c (-0.23% [-0.25%; -0.21%]), triglycerides (-9% [-12%; -7%]), total (-2% [‑3%; ‑1%]), VLDL (-9% [‑11%; -7%]) [all p<0.0001], and LDL (-2% [-4%; -1%]) cholesterol and increase in HDL cholesterol (+2% [1%; 3%]) [both p<0.01]; improved hsCRP (-30% [‑34%; ‑26%]), PAI-1 (-21% [-26%; -17%]) and adiponectin (+8% [5%; 12%]) [all p<0.0001]) occurred.
Conclusion: Over 56 weeks, added to diet and exercise, liraglutide 3.0 mg reduced weight and multiple cardiometabolic risk factors compared with placebo.