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#314 Weight to Go: Naltrexone/bupropion for weight loss

Is naltrexone/bupropion (Contrave®) effective for weight loss?

Over 28-56 weeks, at best, ~50% of patients taking naltrexone/bupropion achieved a >5% loss in body weight, compared to ~20% in control. Naltrexone/bupropion adverse events (examples nausea, constipation) lead to withdrawal in 23% of patients versus 12% on placebo.

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  • Focused on systematic reviews with meta-analysis of randomized, placebo-controlled trials (RCTs). Results statistically significant unless noted.
  • Systematic review, 4 RCTs, 3955 patients who received at least one dose, baseline weight 100kg.1 Both arms included lifestyle changes (e.g., 500kcal/day deficit, increase activity). Naltrexone-bupropion (titrated to 16/180mg BID) versus placebo. At 56 weeks:
    • Participants with ≥5% weight loss: Naltrexone/bupropion 53% versus placebo 21%, number needed to treat (NNT)=4.
    • ≥10% weight loss: Naltrexone/bupropion 29% versus placebo 9%, NNT=5.
    • Mean weight loss (2 RCTs reporting): ~ 6 kg versus ~1 kg control.
    • Withdrawals due to adverse effects: 25% versus 13% placebo, number needed to harm (NNH)=8.
    • Other systematic reviews found similar.2-4
  • Systematic review, same 4 RCTs as above except included lower dosage arm (8/180mg BID) and used all randomized participants, 4536 patients.5
    • Outcomes at 28-56 weeks:
      • ≥5% weight loss: Naltrexone/bupropion 38% versus placebo 17%, NNT=5.
      • ≥10% weight loss: Naltrexone/bupropion 22% versus placebo 8%, NNT=8.
      • Mean weight loss: ~4.5kg versus 2kg (placebo).
      • Withdrawals due to adverse events: 23% versus 12% (placebo), NNH=10.
      • Most common adverse events include nausea (31% versus 7% placebo) and constipation (18% versus 7% placebo).
  • Limitations: All RCTs were industry funded, high dropout rates (~45%), inconsistent magnitude of effects across RCTs but all showed benefit.
  • Trial looking at cardiovascular safety stopped early due to data breach, however, systematic review of 5 RCTs found no association with cardiovascular events.6-7
  • Weight regain after stopping medication unknown.
  • Cost (1 month)8: ~$350 (generally not covered). Off-label prescribing of individual components at lower doses ~$80.
  • Other medications for weight loss include (with mean weight loss in RCTs): Orlistat (~2.6kg)1 or GLP-1 agonists such as semaglutide (~10-15kg)10 or liraglutide (~5kg)11. Baseline weight in studies ~101-106kg.

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  • Betsy Thomas BSc. Pharm
  • Adrienne J Lindblad BSP ACPR PharmD
  • Thao Luu BScPharm PharmD candidate
  • Allison Paige MD CCFP

1. Khera R, Murad MH, Chandar AK, et al. JAMA. 2016 Jun 14; 315(22):2424-34.

2. Singh A, Singh R. Expert Rev Clin Pharmacol. 2020 Jan; 13(1):53-64.

3. Khalil H, Ellwood L, Lord H, et al. Ann Pharmacother. 2020 Jul; 54(7):691-705.

4. LeBlanc EL, Patnode CD, Webber EM, et al. Rockville (MD): Agency for Healthcare Research and Quality (US); 2018 Sep. Report No.: 18-05239-EF-1.

5. Onakpoya IJ, Lee JJ, Mahtani KR, et al. Br J Clin Pharmacol. 2020 Apr; 86(4):646-667.

6. Nissen SE, Wolski KE, Prcela L, et al. JAMA. 2016 Mar 8; 315(10):990-1004.

7. Sposito AC, Bonilha I, Luchiari B, et al. Cardiovascular safety of naltrexone and bupropion therapy: Systematic review and meta-analyses. Obes Rev. 2021 Jun; 22(6):e13224.

8. Alberta Blue Cross Drug Price List effective April 14, 2022. Available at: Accessed on April 14, 2022.

9. Alberta Blue Cross Interactive Drug Benefit List. Available at: Accessed on April 14, 2022.

10. Ojeniran M, Dube B, Paige A, et al. Tools for Practice #295. Available at: Accessed on February 1, 2022.

11. Antony N, Korownyk C. Tools for Practice #168. Available at: Accessed on February 1, 2022.

Authors do not have any conflicts of interest to declare.

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