Tools for Practice Outils pour la pratique


#295 Mission Slimpossible: Semaglutide for weight loss


CLINICAL QUESTION
QUESTION CLINIQUE
Is semaglutide effective for weight loss?


BOTTOM LINE
RÉSULTAT FINAL
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
DONNÉES PROBANTES
  • 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)].
    • 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


Olukayode Fawole August 29, 2021

Very relevant to my practice

Lydia Derzko November 5, 2021

“Weight regain occurs once the medication is stopped? … even if the person maintains positive lifestyle changes?

YS Son December 8, 2021

Weight regain once medication is stopped – this information is really important when treatment is discussed with the patient.

Augustine Opara June 12, 2024

On a lighter, yet sober note – sounds like paying $200 ‘subscription’ a month for 10 – 15% wt loss, if subscription ever cancelled, all the weight comes back. Useful thought while having conversations around initiating semaglutide for wt loss


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

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.

Les auteurs n’ont aucun conflit d’intérêts à déclarer.