Oral Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2014

Liraglutide 3.0 mg Reduces the Prevalence of Prediabetes and Delays Onset of Type 2 Diabetes in Overweight and Obese Adults: Results from SCALE Obesity and Prediabetes, a Randomized, Double-blind and Placebo-controlled 56-week Trial (#100)

Xavier Pi-Sunyer 1 , Arne Astrup 2 , Ken Fujoka 3 , Frank Greenaway 4 , Alfredo Halpern 5 , Michael Krempf 6 , David CW Lau 7 , Carel W le Roux 8 , Rafael Violante Ortiz 9 , Christine Bjørn Jensen 10 , John Wilding 11 , Ian Caterson 12
  1. Columbia University, New York, NY, USA
  2. Department of Nutrition Exercise and Sports, University of Copenhagen, Copenhagen, Denmark
  3. Division of Endocrinology, Scripps Clinic, La Jolla, California, USA
  4. Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA
  5. Obesity & Metabolic Syndrome Unit, Division of Endocrinology & Metabolism, Hospital das Clínicas, University of São Paulo Medical School, Sao Paulo, Brazil
  6. Clinique d’endocrinologie et Nutrition, Université de Nantes, Nantes, France
  7. Departments of Medicine and Biochemistry & Molecular Biology, University of Calgary, Calgary, Alberta, Canada
  8. Diabetes Complications Research Centre, University College Dublin, Dublin, Ireland
  9. Departamento Endocrinología, Instituto Mexicano del Seguro Social, Hospital Regional num. 6, Cd.Madero, Tam, Mexico
  10. Novo Nordisk A/S, Soeborg, Denmark
  11. Department of Obesity and Endocrinology, University of Liverpool, Liverpool, UK
  12. University of Sydney, University Of Sydney, NSW, Australia
Obesity is associated with prediabetes, a risk factor for developing T2D. We investigated the effects of liraglutide 3.0mg, as adjunct to diet and exercise (D&E), on weight loss, prediabetes prevalence and onset of T2D over 56 weeks. Effects of liraglutide cessation were investigated in a 12‑week re-randomized period. Adults (BMI ≥27kg/m2 with ≥1 comorbidity or ≥30kg/m2) received 500kcal/day deficit diet and exercise. Randomization was 2:1 to once-daily s.c. liraglutide 3.0 mg (n=2487) or placebo (n=1244), stratified by prediabetes status. At week 56, individuals without prediabetes on liraglutide were re-randomized 1:1 to liraglutide or placebo (D&E continued). Clinicaltrials.gov ID: NCT01272219. Of 3731 individuals (age 45.1 years, 78.5% female, weight 106.2kg, BMI 38.3kg/m2, 61.2% with prediabetes), 71.9% on liraglutide and 64.4% on placebo completed study. Data are observed means/proportions from the full analysis set with LOCF. Statistical analysis is ANCOVA (continuous endpoints) or logistic regression (categorical endpoints). After 56 weeks, individuals on liraglutide lost 8.0% (8.4kg) weight versus 2.6% (2.8kg) on placebo (estimated treatment difference [ETD] 5.4% [5.6kg], p<0.0001). Liraglutide improved fasting and post-load glycaemia versus placebo (ETD FPG -0.38mmol/L, PG [OGTT, AUC] 2.02 h*mmol/L, HbA1c ‑0.23%-points; p<0.0001 for all). More individuals reverted to normoglycaemia on liraglutide than placebo (69.2% vs. 32.7%; odds ratio [OR] 4.85, p<0.0001). More individuals taking placebo progressed to prediabetes (20.7% vs. 7.2%; OR 3.3, p<0.0001) or developed T2D (n=14, 1.3 events/100 patient years of exposure [PYE]) than liraglutide (n=4, 0.2 events/100 PYE; OR 8.06, p=0.0003). From week 56–68, individuals re-randomized to placebo regained more weight (2.9% vs. 0.7%; ETD 2.2%, p<0.0001) and progressed to prediabetes (8.0–22.4% vs. 9.1–8.6%; p<0.0001) than individuals on liraglutide. No-one developed T2D. Consistent with effects on weight and glycaemia, liraglutide 3.0mg was superior to placebo in reducing prevalence of prediabetes and T2D. Continued treatment was required to sustain these effects.