Exp Clin Endocrinol Diabetes 2015; 123 - LB_20
DOI: 10.1055/s-0035-1549086

Efficacy and safety of liraglutide 3.0 mg for weight management in overweight and obese adults: the SCALE™ Obesity and Prediabetes, a randomised, double-blind and placebo-controlled trial

M Blüher 1, J Wilding 2, A Astrup 3, K Fujioka 4, F Greenway 5, A Halpern 6, M Krempf 7, D Lau 8, CW le Roux 9, R Violante Ortiz 10, NS Schaaf 11, CB Jensen 12, X Pi-Sunyer 13
  • 1Universitätsklinikum Leipzig, Klinik und Poliklinik für Endokrinologie und Nephrologie, Deutschland
  • 2Department of Obesity and Endocrinology, University Hospital Aintree, Liverpool L97AL, England
  • 3Department of Nutrition, Exercise and Sports, University of Copenhagen, DK-1958 Frederiksberg C, Denmark.
  • 4Division of Endocrinology, Department of Nutrition and Metabolic Research, Scripps Clinic, La Jolla, California 92130, USA
  • 5Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA
  • 6Obesity & Metabolic Syndrome Unit, Division of Endocrinology & Metabolism, Hospital das Clínicas, University of São Paulo Medical School, São Paulo 01406 – 100, Brazil.
  • 7Clinique d'endocrinologie et Nutrition, Université de Nantes, 44093 Nantes Cedex 1, France
  • 8Departments of Medicine and Biochemistry & Molecular Biology, University of Calgary, Calgary, Alberta, Canada T2N 4N1
  • 9Diabetes Complications Research Centre, University College Dublin, Ireland
  • 10Departamento Endocrinología, Instituto Mexicano del Seguro Social, Hospital Regional num. 6 Cd. Madero, Tam. México
  • 11Novo Nordisk Pharma GmbH, Mainz, Deutschland
  • 12Novo Nordisk A/S, DK-2860 Soeborg, Denmark
  • 13St Luke's – Roosevelt Hospital Center, Columbia University, New York, NY 10025, USA

Introduction:

The 56-week efficacy and safety of liraglutide 3.0 mg, as adjunct to diet and exercise, was investigated in overweight and obese individuals without T2DM.

Methods:

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. Randomisation was stratified by prediabetes status (ADA 2010) and BMI. Clinicaltrials.gov ID: NCT01272219.

Results:

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 (WL) related parameters (Table) and improved glycaemia, blood pressure and lipids (not shown). WL was independent of pre-treatment prediabetes status and BMI. The most common adverse events (AEs) with liraglutide were early onset nausea and diarrhoea. Most events were 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 (1.1 and 0.1 events/100 PYE). AE withdrawal was < 10% in both groups. The safety profile was generally consistent with that of previous clinical trials with liraglutide for T2DM.

Tab. 1: Change baseline to 56-weeks, full-analysis-set, last-observation-carried-forward

Liraglutide

LS-mean

[95% CI]

Placebo

LS-mean

Estimated treatment-

difference/Odds ratio

1. WL (%)*

-8.0

-2.6

-5.4 [-5.8; -5.0] p < 0.0001**

2. 5% responders (%)*

63.5

26.6

4.8 [4.1; 5.6] p < 0.0001***

3. 10% responders (%)*

32.8

10.1

4.3 [ 3.5; 5.3] p < 0.0001***

Waist circumference (cm)

-8.2

-4.0

-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 in hierarchical order

**ANCOVA

***Logistic-regression

Conclusion: Liraglutide 3.0 mg, as adjunct to diet and exercise, was efficacious and generally well tolerated.