semaglutide in the treatment of obesity

Last edited 10/2023 and last reviewed 11/2023

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

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