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Semaglutide in the treatment of obesity

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

Authoring team

Comparison between liraglutide and semaglutide in treatment of obesity (1):

  • randomized (3:1:3:1) to receive once-weekly subcutaneous semaglutide, 2.4 mg (16-week escalation; n = 126), or matching placebo, or once-daily subcutaneous liraglutide, 3.0 mg (4-week escalation; n = 127), or matching placebo, plus diet and physical activity
  • randomized clinical trial that included 338 participants, mean body weight change from baseline to 68 weeks was -15.8% with semaglutide vs -6.4% with liraglutide, a statistically significant difference

NICE guidance states (2):

  • Semaglutide is recommended as an option for weight management, including weight loss and weight maintenance, alongside a reduced-calorie diet and increased physical activity in adults, only if:
    • it is used for a maximum of 2 years, and within a specialist weight management service providing multidisciplinary management of overweight or obesity (including but not limited to tiers 3 and 4), and
    • they have at least 1 weight-related comorbidity and:
      • a body mass index (BMI) of at least 35.0 kg/m2, or
      • a BMI of 30.0 kg/m2 to 34.9 kg/m2 and meet the criteria for referral to specialist weight management services
    • use lower BMI thresholds (usually reduced by 2.5 kg/m2) for people from South Asian, Chinese, other Asian, Middle Eastern, Black African or African-Caribbean family backgrounds
  • the company provides semaglutide according to the commercial arrangement
  • Consider stopping semaglutide if less than 5% of the initial weight has been lost after 6 months of treatment

The NICE committee state (2):

  • "...Clinical trial evidence shows that:
    • people lose more weight with semaglutide alongside supervised weight management support than with the support alone
    • more weight is lost with semaglutide than with liraglutide
    • in people with non-diabetic hyperglycaemia, semaglutide plus lifestyle measures helps normalise blood glucose more frequently than lifestyle measures alone
    • semaglutide may decrease the risk of cardiovascular disease.."

In the OASIS 1 study:

  • in adults with overweight or obesity without type 2 diabetes, oral semaglutide 50 mg once per day led to a superior and clinically meaningful decrease in bodyweight compared with placebo (3)
    • estimated mean bodyweight change from baseline to week 68 was -15.1% with oral semaglutide 50 mg versus -2.4% with placebo
    • gastrointestinal adverse events (mostly mild to moderate) were reported in 268 (80%) participants with oral semaglutide 50 mg and 154 (46%) with placebo

Use of glucagon like peptide-1 (GLP-1) receptor agonists for weight loss has been linked to an increased risk of pancreatitis, gastroparesis, and bowel obstruction (4)

  • study evidence showed that GLP-1 agonists are associated with increased risk of pancreatitis (HR 9.1), bowel obstruction (HR 4.2) and gastroparesis (HR 3.7) when compared with bupropion-naltrexone for weight loss
    • based on a comparison of outcomes in 4144 non-diabetic patients using liraglutide, 613 using semaglutide and 654 using bupropion-naltrexone, it was calculated that the incidence of biliary disease was 18.6 per 1000 person-years for liraglutide, 11.7 for semaglutide and 12.6 for bupropion. For pancreatitis the incidence rates were 7.9, 4.6 and 1.0 respectively

The STEP7 study (n=375)

  • investigated the use of once weekly GLP-1 receptor agonist semaglutide 2·4 mg for weight management in people from east Asia
    • found semaglutide 2.4mg/week resulted in greater weight loss at 44 weeks vs placebo (estimated mean percentage weight change −12.1% [SE 0.5] vs −3.6% [0.7]) and greater proportion of patients with loss of ≥ 5% bodyweight (85% vs 31% placebo)
    • study authors noted that results of this study support the use of semaglutide 2·4 mg for weight management in people of east Asian ethnicity with overweight or obesity and with or without type 2 diabetes

Reference:

  • 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;327(2):138-150. doi:10.1001/jama.2021.23619
  • NICE (Sept 2023). Semaglutide for managing overweight and obesity
  • Knop FK et al. Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet June 25, 2023
  • Mahase E. GLP-1 agonists linked to adverse gastrointestinal events in weight loss patients BMJ 2023; 383 :p2330 doi:10.1136/bmj.p2330
  • Mu Y et al. Efficacy and safety of once weekly semaglutide 2·4 mg for weight management in a predominantly east Asian population with overweight or obesity (STEP 7): a double-blind, multicentre, randomised controlled trial. Lancet Diabetes and Endocrinology February 05, 2024

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