Oral Presentation Australian & New Zealand Obesity Society 2016 Annual Scientific Meeting

Liraglutide 3.0 mg reduces body weight and improves cardiometabolic risk factors in adults with obesity or overweight, but without diabetes: the SCALE Obesity and Prediabetes randomised, double-blind, placebo-controlled 3-year trial (#78)

Tania Markovic 1 , Arne Astrup 2 , Frank Greenway 3 , Michel Krempf 4 , Carel W Le Roux 5 , Roberto Vettor 6 , Linda Shapiro Manning 7 , Søren K Lilleøre 7 , Ken Fujioka 8
  1. Garvan Institue of Medical Research, Darlinghurst, NSW
  2. University of Copenhagen, Frederiksberg, Denmark
  3. Pennington Biomedical Research Center, Baton Rouge, LA, USA
  4. Université de Nantes, Nantes, France
  5. University College Dublin, Dubllin, Ireland
  6. University of Padua, Padua, Italy
  7. Novo Nordisk A/S, Soeborg, Denmark
  8. 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. Clinicaltrials.gov 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.