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#168 Liraglutide: Weighing the evidence for weight loss?


CLINICAL QUESTION
QUESTION CLINIQUE
Does liraglutide reduce weight and improve health in obese patients?


BOTTOM LINE
RÉSULTAT FINAL
Once daily Liraglutide 3.0 mg injections reduce weight 3.4%-4.6 % over one year and one in 3-4 patients treated will get a 5% weight loss over placebo. Adverse events (like nausea and vomiting) will cause one in 17 to stop liraglutide. The effect was not sustained beyond drug cessation and long-term health effects in obese non-diabetics are unknown.   



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EVIDENCE
DONNÉES PROBANTES
  • Primarily two large industry-funded randomized controlled trials (RCTs) assessing liraglutide injection for weight loss:
    • 3,731 non-diabetic obese (mean 106 kg) patients.1 Over 56 weeks, daily 3.0 mg liraglutide versus placebo resulted in:
      • Intention to treat analysis:2 4.6% (5 kg) reduction in total body weight. 
      • 63% versus 27% lost ≥5% body weight, Number Needed to Treat (NNT)=3.
      • 33% versus 11% lost >10% body weight, NNT=5. 
      • 12 weeks after stopping, subjects regained ~2.9% initial body weight.
    • 846 diabetic obese (mean 106 kg) patients, 3.0 mg, 1.8 mg liraglutide, or placebo for 56 weeks.3
      • Weight loss compared to placebo for 3.0 mg and 1.8 mg liraglutide was: 
        • Intention to treat analysis:2 3.4% and 2.5% respectively. 
      • 3.0 mg liraglutide versus placebo:
        • 54% versus 21% lost ≥5% body weight, NNT=4. 
        • 25% versus 7% lost ≥10% body weight, NNT=6.
    • Adverse Events: Nausea [Number Needed to Harm (NNH)~4] and vomiting (NNH ~9).2
      • Withdrawal due to adverse events:4 10% Liraglutide versus 4% placebo, NNH=17.  
    • Smaller RCTs support these findings.5,6
  Context:  
  • 5% weight loss is suggested as potentially meaningful.7 However, 17% weight loss was needed for the severely obese (BMI 46-49) to attain a minimally clinically significant improvement in quality of life.8
  • Liraglutide 1.8 mg is indicated for Type 2 Diabetes9 and 3.0 mg dose for weight loss.10
    • Canadian cost for 3.0 mg liraglutide is ~$400/month. 
  • Fit-obese individuals have similar mortality to fit-normal weight individuals.11  
  • In diabetic patients (mean BMI 32 and weight 92 kg), liraglutide led to a 13% relative reduction in cardiovascular events (NNT=53) over ~4 years.12  
    • Long-term outcomes in obese non-diabetics are unknown.


gregory Stroh April 29, 2024

Interesting


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Author(s)
Auteur(s)
  • Christina Korownyk MD CCFP
  • Nikytha Antony BHSc

1. Pi-Sunyer X, Astrup A, Fujioka K, et al. N Engl J Med. 2015; 373:11-22.

2. Endocrinologic and Metabolic Drug Advisory Committee. Summary review for regulatory action NDA 206-321 2014. FDA Sept 11, 2014. Available from: http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/endocrinologicandmetabolicdrugsadvisorycommittee/ucm413317.pdf. Last accessed June 27, 2016.

3. Davies MJ, Bergenstal R, Bode B, et al. JAMA. 2015; 314:687-99.

4. Khera R, Murad MH, Chandar AK, et al. JAMA. 2016; 315:2424-34.

5. Wadden TA, Hollander P, Klein S, et al. Int J Obes (Lond). 2013; 37:1443-51.

6. Astrup A, Carraro R, Finer N, et al. Int J Obes (Lond). 2012; 36(6):843-54.

7. Institute of Medicine, National Academy of Sciences. Weighing the Options: Criteria for Evaluating Weight Management Programs. Government Printing Office: Washington, DC, 1995.

8. Warkentin LM, Majumdar SR, Johnson JA, et al. BMC Medicine. 2014; 12:175.

9. Product Monograph. Victoza liraglutide 6mg/ml solution for injection in a pre-filled pen. Novo Nordisk Canada Inc. April 19, 2016.

10. Product Monograph. Saxenda liraglutide 6mg/ml solution for injection in a pre-filled pen. Novo Nordisk Canada Inc. March 11, 2016.

11. Barry VW, Baruth M, Beets MW, et al. Prog Cardiovasc Dis. 2014; 56:382-90.

12. Marso SP, Daniels GH, Brown-Frandsen K, et al. N Engl J Med. 2016 Jun 13. [Epub ahead of print]

Authors do not have any conflicts to disclose.