liraglutide in obesity

Last edited 05/2021 and last reviewed 11/2021

Liraglutide is a glucagon like peptide-1 GLP-1) receptor agonist

  • Victoza (R) is a 1.8 mg daily subcutaneous injection of liraglutide that was initially approved by the FDA in 2010 as an adjunct therapy to diet and exercise for management of type 2 diabetes (1)
    • results from clinical trials repeatedly demonstrated the ability of GLP-1 analogs to induce weight loss - as a result, liraglutide was also developed as a weight loss agent and its 3.0 mg daily dose (Saxenda (R))
        • liraglutide 3 mg led to decreases in body weight of >5% to as much as 15% (2)

GLP-1 is a polypeptide incretin hormone secreted by the L-cells of the gastrointestinal tract in response to nutrients in the lumen.

  • GLP-1 causes (1):
      • a glucose dependent stimulation of insulin secretion
      • reduction in plasma glucagon concentrations
      • delayed gastric emptying
      • appetite suppression
      • and an increase in heart rate
    • appetite suppression and delayed gastric emptying are thought to be responsible for the weight lowering effects of GLP-1 (1)
  • a 5%-10% reduction in body weight in overweight and obese individuals improves several risk factors for cardiovascular disease (CVD), including elevated blood glucose, blood pressure, and plasma triglyceride concentrations

NICE have stated that (4):

  • Liraglutide is recommended as an option for managing overweight and obesity alongside a reduced-calorie diet and increased physical activity in adults, only if:
    • they have a body mass index (BMI) of at least 35 kg/m2 (or at least 32.5 kg/m2 for members of minority ethnic groups known to be at equivalent risk of the consequences of obesity at a lower BMI than the white population) and

    • they have non-diabetic hyperglycaemia (defined as a haemoglobin A1c level of 42 mmol/mol to 47 mmol/mol [6.0% to 6.4%] or a fasting plasma glucose level of 5.5 mmol/litre to 6.9 mmol/litre) and

    • they have a high risk of cardiovascular disease based on risk factors such as hypertension and dyslipidaemia and

    • it is prescribed in secondary care by a specialist multidisciplinary tier 3 weight management service and

    • the company provides it according to the commercial arrangement

Liraglutide plus exercise in weight loss management

  • in a Danish randomised controlled trial involving 195 people with obesity (5)
    • the combination of a moderate-to-vigorous-intensity exercise program and liraglutide treatment after diet-induced weight loss was more effective in improving healthy weight loss than exercise alone, at 1 year follow-up
    • participants were randomly assigned for 1 year to one of four strategies:
      • a moderate-to-vigorous–intensity exercise program plus placebo (exercise group);
      • treatment with liraglutide (3.0 mg per day) plus usual activity (liraglutide group);
      • exercise program plus liraglutide therapy (combination group);
      • or placebo plus usual activity (placebo group)
    • end points with prespecified hypotheses in the study were the change in body weight (primary end point) and the change in body-fat percentage (secondary end point) from randomization to the end of the treatment period in the intention-to-treat population. Prespecified metabolic health-related end points and safety were also assessed
    • all the active-treatment strategies led to greater weight loss than placebo: difference in the exercise group
      • - 4.1 kg in the exercise group
      • - 6.8 kg in the liraglutide group
      • -9.5 kg and in the combination group
        • combination strategy decreased body-fat percentage by 3.9 percentage points, which was approximately twice the decrease in the exercise group
        • only the combination strategy was associated with improvements in the glycated hemoglobin level, insulin sensitivity, and cardiorespiratory fitness
    • conclusion
      • a strategy combining exercise and liraglutide therapy improved healthy weight loss maintenance more than either treatment alone

Notes:

  • the dose of liraglutide for obesity (see summary of product characteristics for full details):
    • starting dose is 0.6 mg once daily. The dose should be increased to 3.0 mg once daily in increments of 0.6 mg with at least one week intervals to improve gastro-intestinal tolerability

Reference:

Related pages:

obesity

liraglutide

prediabetes