Tools for Practice


#295 Mission Slimpossible: Semaglutide for weight loss


CLINICAL QUESTION
Is semaglutide effective for weight loss?

BOTTOM LINE
Used with lifestyle changes, 2.4mg weekly subcutaneous semaglutide resulted in an average 10-15% loss in weight (10-15kg) over 68 weeks versus 2-3% (3-4kg) with placebo. Most (70-80%) semaglutide participants lost 5% or more of their body weight. About ¾ of patients experienced gastrointestinal side effects, but few stop. Weight regain occurs once the medication is stopped.


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EVIDENCE
  • Four industry-funded, randomized, placebo-controlled trials (RCTs) of subcutaneous semaglutide 2.4mg/week for weight loss, plus lifestyle interventions (counseling, diet, and physical activity).1-4 Baseline weight ~96-105kg.
    • 1961 non-diabetics.1 After 68 weeks:
      • Mean weight loss: 15% of weight (15kg) versus 2% (3kg, placebo).
      • Proportion who lost ≥5% weight: 86% versus 32% (placebo), number need to treat (NNT)=2.
        • Lost ≥10%: 69% versus 12%, NNT=2.
        • Weight loss plateaued ~week 60.
      • Adverse effects:
        • Gastrointestinal: 74% versus 48% (placebo), number needed to harm (NNH)=3.
        • Withdrawal due to adverse effects: 7% versus 3%, NNH=25.
    • RCT of semaglutide with more intensive lifestyle intervention found similar [weight loss 16% (17kg) versus 6% (6kg, placebo)].2 
    • Dose-finding RCT, 1210 diabetics. Given semaglutide 2.4mg/week, 1.0mg/week or placebo.3 After 68 weeks:
      • Mean weight loss: 10% (2.4mg), 7% (1mg) and 3% (placebo)
      • Proportion who lost ≥5% weight: 69% (2.4mg) versus 57% (1mg) versus 29% (placebo), 2.4mg versus 1mg: NNT=9.
      • Adverse effects similar between doses.
    • Weight maintenance RCT. 803 non-diabetics given semaglutide 2.4mg/week for 20 weeks then randomized to continue semaglutide or switch to placebo. After 48 weeks:4
      • Continued semaglutide lost 8% versus 7% gain (placebo).
Context
  • Weight loss with oral semaglutide studied as secondary outcome in cardiovascular disease and glucose-lowering trials. Participants weight loss was 4.6% (4.2kg) versus 0.9% (0.8kg, placebo) at 15.9 months in largest RCT.5
  • High-dose semaglutide (0.4mg daily) superior to liraglutide (3mg daily) in semaglutide-sponsored RCT:
    • Weight loss: 14% semaglutide (17kg) versus 8% liraglutide (8kg).
    • Weight loss similar between 0.1mg daily semaglutide and liraglutide.6
  • Semaglutide titration in RCTs: Every 4 weeks as tolerated.
  • Semaglutide 2.4mg not currently available (Canada), but lower doses are.7
    • 1mg weekly costs ~$200/month.8
July 26, 2021

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Author(s):

  • Adrienne J Lindblad BSP ACPR PharmD
  • Allison Paige MD CCFP
  • Betty Dube BPharm MSc(Pharm) R.Ph
  • Joey Ton BScPharm PharmD
  • Mo Ojeniran BPharm MPH R.Ph

1. Wilding JPH, Batterham RL, Calanna S, et al. NEJM. 2021; 384:989-1002.

2. Wadden TA, Bailey TS, Billings LK, et al. JAMA. 2021; 325(14):1403-13.

3. Davies M, Færch L, Jeppesen OK, et al. Lancet. 2021 Mar 13; 397(10278):971-984.

4. Rubino D, Abrahamsson N, Davies M, et al. JAMA. 2021 Apr 13; 325(14):1414-1425.

5. Husain M, Birkenfeld AL, Donsmark M, et al. N Engl J Med. 2019; 381:841-51.

6. O’Neil PM, Birkenfeld AL, McGowan B, et al. Lancet. 2018; 392:637-49.

7. Health Canada Drug Product Database. Available at: https://health-products.canada.ca/ Accessed: June 29, 2021.

8. PEER/Alberta College of Family Physicians. Price Comparison of Commonly Prescribed Pharmaceuticals in Alberta 2021. Available at: https://pricingdoc.acfp.ca/ Accessed April 30, 2021.

Authors do not have any conflicts of interest to declare.