Liraglutide in prediabetes

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

NICE recommends liraglutide as an option for adults only if: (1)

• they have a BMI ≥35 kg/m² (or ≥32.5 kg/m² for members of ethnic groups known to be at greater risk)
• 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)
• a high risk of cardiovascular disease
• and if prescribed by a specialist weight management service

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 (2)

GLP-1 is a polypeptide incretin hormone secreted by the L-cells of the gastrointestinal tract in response to nutrients in the lumen and causes (2):

• 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 (2)

• 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

Liraglutide plus exercise in weight loss management

• in a Danish randomised controlled trial involving 195 people with obesity (3)
  • 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 haemoglobin 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
  • in one trial comparing use of semaglutide or liraglutide in addition to behavioural modifications, patients receiving semaglutide had significantly greater weight loss (4)

References:

1. National Institute for Health and Care Excellence. Liraglutide for managing overweight and obesity [TA664]. December 2020 [internet publication].
2. Mehta A et al. Liraglutide for weight management: a critical review of the evidence.Obes Sci Pract. 2017 Mar; 3(1): 3-14.
3. Lundgren JR et al. Healthy Weight Loss Maintenance with Exercise, Liraglutide, or Both Combined. N Engl J Med. 2021 May 6;384(18):1719-1730.
4. Rubino DM, Greenway FL, Khalid U, et al. Effect of weekly subcutaneous semaglutide vs daily liraglutide on body weight in adults with overweight or obesity without diabetes: the STEP 8 randomized clinical trial. JAMA. 2022 Jan 11;327(2):138-50.