Poster Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2016

Weight loss and associated improvements in cardiometabolic risk factors with liraglutide 3.0 mg in the SCALE Obesity and Prediabetes randomised, double-blind, placebo-controlled 3-year trial (#247)

Trisha O'Moore-Sullivan 1 , Arne Astrup 2 , Frank Greenway 3 , Michel Krempf 4 , Carel Le Roux 5 , Roberto Vettor 6 , Linda Shapiro Manning 7 , Søren K Lilleøre 7 , Ken Fujioka 8
  1. Mater Health Services, South Brisbane, QLD, Australia
  2. Nutrition, Exercise and Sports, University of Copenhagen, Frederiksberg, Denmark
  3. Pennington Biomedical Research Center, Baton Rouge, LA, USA
  4. Clinique d’endocrinologie et Nutrition, Université de Nantes, Nantes, France
  5. Diabetes Complications Research Centre, Conway Institute, University College Dublin, Dubllin, Ireland
  6. Internal Medicine 3 Center for the Study and the Integrated Treatment of Obesity , University of Padua, Padua, Italy
  7. Novo Nordisk A/S, Soeborg, Denmark
  8. Nutrition and Metabolic Research , Scripps Clinic, La Jolla, CA, USA

Aims/Objectives: Obesity and prediabetes are risk factors for developing T2D. 5-10% weight-loss can reduce risk of developing T2D by >50%. This phase-3 trial investigated effects of liraglutide 3.0mg, as adjunct to diet+exercise, on delaying onset of T2D over 3 years (primary endpoint), body-weight and cardiometabolic risk factors.

Methods: Individuals (BMI ≥30kg/m2, or ≥27kg/m2 with ≥1 comorbidity) were randomised 2:1 to once-daily subcutaneous liraglutide 3.0mg (n=1505) or placebo (n=749) and advised on a 500-kcal/day deficit diet and 150-min/week exercise. Efficacy data are observed means, with last-observation-carried-forward (LOCF) imputation. NCT01272219.

Results: Baseline characteristics were (mean±SD): age 47.5±11.7 years, 76.0% female, weight 107.6±21.6kg, BMI 38.8±6.4kg/m2. With continued treatment over 160 weeks, time to T2D onset was 2.7-fold longer with liraglutide 3.0mg than placebo [95%CI 1.9;3.9, p<0.0001], corresponding to a hazard ratio of 0.2; 3% vs 11% of patients, respectively were diagnosed with T2D. More individuals on liraglutide (66%) than placebo (36%) regressed from prediabetes (ADA2010 criteria) to normoglycaemia by week 160 (OR 3.6 [3.0;4.4], p<0.0001). Individuals on liraglutide 3.0 mg lost more weight than on placebo (6.1% vs 1.9%; estimated treatment difference [ETD] -4.3% [95%CI ‑4.9;-3.7]), accompanied by greater mean reductions in waist circumference (ETD ‑3.5 [‑4.2;‑2.8] cm), SBP (ETD ‑2.8 [-3.8;-1.8] mmHg), triglycerides (ETD -6%[‑9;-3]) and high-sensitivity C-reactive protein (ETD 29% [-34;-23]) (all p<0.001). Mean pulse increased with liraglutide 3.0mg vs placebo (ETD 2.0 [1.2;2.7] beats/min, p<0.0001). AE incidence was 94.7% with liraglutide 3.0mg vs 89.4% with placebo, SAEs 15.1% vs 12.9%. Adjudicated major adverse cardiovascular events (non-fatal myocardial infarction, stroke, cardiovascular death) were low overall (0.19 vs 0.20 events/100 patient-years-of-observation for liraglutide 3.0mg vs placebo).

Conclusion: Liraglutide 3.0mg, as adjunct to diet+exercise, delayed the onset and reduced the risk of T2D over 3 years in adults with prediabetes, reduced body weight and improved cardiometabolic risk factors.

Supported by Novo Nordisk.