The 56-week efficacy and safety of liraglutide 3.0 mg, as adjunct to diet and exercise, were investigated in overweight and obese individuals without type 2 diabetes (T2D). Adults (BMI ≥27 kg/m2 with comorbidities or ≥30 kg/m2) were randomised 2:1 to once-daily subcutaneous liraglutide or placebo plus diet (500 kcal/day deficit) and exercise. 3731 individuals were randomised (age 45.1±12.1 years, body weight 106.2±21.4 kg, BMI 38.3±6.4 kg/m2, 61.2% with prediabetes). Liraglutide was superior to placebo on all weight loss-related parameters (Table) and improved glycaemia, blood pressure and lipids. Weight loss was independent of pre-treatment prediabetes status and BMI. The most common adverse events (AEs) with liraglutide were early-onset nausea and diarrhoea (mostly mild/moderate and transient). Gallbladder disorders and pancreatitis were more common with liraglutide (2.7 and 0.3 events/100 patient-years of exposure [PYE], respectively) than with placebo (1.0 and 0.1 events/100 PYE). AE withdrawal was <10% in both groups. The safety profile was generally consistent with previous trials with liraglutide for T2D. In conclusion, liraglutide 3.0 mg, as adjunct to diet and exercise, was efficacious and generally well tolerated.
Table – Change from baseline to week 56, full analysis set, last observation carried forward
Liraglutide (n=2432) Observed mean |
Placebo (n=1220) Observed mean |
Estimated treatment-difference/Odds ratio [95% CI] |
|
Weight loss (%)* |
-8.0 |
-2.6 |
-5.4 [-5.8;-5.0] p<0.0001** |
5% responders (%)* |
63.2 |
27.1 |
4.8 [4.1;5.6] p<0.0001*** |
10% responders (%)* |
33.1 |
10.6 |
4.3 [ 3.5;5.3] p<0.0001*** |
Waist circumference (cm) |
-8.2 |
-3.9 |
-4.2 [-4.7;-3.7] p<0.0001** |
BMI (kg/m2) |
-3.0 |
-1.0 |
-2.0 [-2.2;-1.9] p<0.0001** |
*Co-primary endpoints tested hierarchically
**ANCOVA
***Logistic-regression