#168 Liraglutide: Weighing the evidence for weight loss?

CLINICAL QUESTION

Does liraglutide reduce weight and improve health in obese patients?

BOTTOM LINE

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

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.

August 15, 2016

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Author(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.