Liraglutide 3.0 mg: weight-loss dependent and independent effects — ASN Events
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Liraglutide 3.0 mg: weight-loss dependent and independent effects (#305)

Luc van Gaal 1 , Joanna Uddén Hemmingsson 2 , Xavier Pi-Sunyer 3 , Christine B Jensen 4 , Sabina Furber 5 , Harold Bays 6
  1. University Hospital, Antwerp, Antwerp, ANTWERP, Belgium
  2. Capio St Göran’s Hospital / Karolinska Institutet, Stockholm, Sweden
  3. St Luke’s-Roosevelt Hospital Center, Columbia University, New York, NY, USA
  4. Novo Nordisk A/S, Søborg, Denmark
  5. Novo Nordisk Pharmaceuticals, Sydney, NSW, Australia
  6. L-MARC Research Center, Louisville, KY, USA

Liraglutide 3.0 mg may benefit individuals with obesity via weight-loss dependent and independent effects. The SCALE phase 3 clinical trial programme examined the efficacy and safety of liraglutide 3.0 mg in overweight or obese individuals (n=4936) with or without prediabetes (NCT01272219), type 2 diabetes (NCT01272232), or obstructive sleep apnoea (NCT01557166). Across all these trials, liraglutide 3.0 mg vs. placebo reduced mean body weight by 5.7–8.0% vs. 0.2–2.6% and waist circumference by 4.7–8.2 cm vs. 1.2–4.0 cm, respectively (all p<0.0001). Liraglutide 3.0 mg also significantly improved secondary endpoints such as HbA1c, fasting plasma glucose (FPG), blood pressure, lipid profile, and reduced concomitant use of glucose-lowering, lipid-lowering and antihypertensive medications. Health-related quality of life (QoL) scores and the apnoea-hypopnoea index (AHI) also improved.

Mediation analysis is a tool that may help to explain the observed effects and investigate the underlying mechanisms. This post hoc mediation analysis investigated the direct and indirect effects of liraglutide 3.0 mg on several secondary efficacy endpoints using weight loss as potential mediator. Data were derived from the SCALE Obesity and Prediabetes. In addition, glycaemic endpoints (HbA1c, FPG), and use of oral anti-diabetic drugs (OADs) were included from the SCALE Diabetes and Sleep Apnoea trials, and AHI from the SCALE Sleep Apnoea trial. The effect of liraglutide-induced weight loss on several secondary endpoints was ranked between 0 and 100%; 100% indicting complete mediation by weight loss. Endpoints primarily driven by weight loss included waist circumference, diastolic blood pressure, triglycerides and HDL cholesterol levels, AHI, IWQoL-Lite total, and physical function scores (ranked 88–100%). Endpoints predominantly independent of weight loss included glycaemic endpoints and use of OADs (ranked 18–32%). For each endpoint, including those driven by weight-loss independent mechanisms, weight loss was a significant contributor to the treatment effect. In individuals with overweight or obesity, treatment with liraglutide 3.0 mg contributes to improved secondary endpoints through both weight-loss-dependent and weight-loss-independent effects.