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Naltrexon/bupropion for obesity


The slimming product Mysimba®, a combination of naltrexon and bupropion, was recently included in the Dutch drug reimbursement system (Geneesmiddelenvergoedingssysteem, GVS). The drug is fully reimbursed under the national basic health insurance package, though with specific preconditions, including its use together with the Dutch programme known as combined lifestyle intervention (CLI). Its inclusion in the GVS was reported in the Dutch TV news on Tuesday 24 May 2022. Despite what this media attention suggests, results achieved with naltrexon/bupropion in terms of weight loss have been disappointing, and it is to be expected that over a third of users will discontinue the treatment for this reason. A study using cardiovascular endpoints yielded no conclusions, as it was prematurely ended. There is therefore no reason to recommend this drug to obese patients in practice.

  • The proportion of people who reduce their weight by more than 5 or 10% by treatment with naltrexon/bupropion is higher than with combined lifestyle intervention alone. The average weight loss compared to placebo is less than 5%.
  • The results are biased, for one thing by the fact that participants with insufficient weight loss or who were unable to tolerate the treatment, were removed from the study after 16 weeks.
  • The use of naltrexon/bupropion was associated with significantly more gastrointestinal, psychiatric and central adverse effects than placebo.
  • No health gains could be proven on cardiovascular end points.
  • Large-scale use of naltrexon/bupropion for the treatment of obesity should be discouraged.

  1. De Vries S. Farmacotherapeutisch rapport naltrexon/bupropion (Mysimba®) voor gewichtsbeheersing bij volwassen patiënten met obesitas of overgewicht in combinatie met een comorbiditeit. 15 maart 2022. Available from: https://www.zorginstituutnederland.nl/publicaties/adviezen/2022/05/17/gvs-advies-naltrexon-in-combinatie-met-bupropion-mysimba. Accessed 21-07-2022.
  2. Verpeut JL, Bello NT. Drug safety evaluation of naltrexone/bupropion for the treatment of obesity. Expert Opin Drug Saf. 2014 Jun;13(6):831-41. doi: 10.1517/14740338.2014.909405. Epub 2014 Apr 28. PMID: 24766397.
  3. Anoniem. De medicamenteuze behandeling van overgewicht. Gebu. 2015;49(10):111-8.
  4. Nissen SE, Wolski KE, Prcela L, Wadden T, Buse JB, Bakris G, Perez A, Smith SR. Effect of Naltrexone-Bupropion on Major Adverse Cardiovascular Events in Overweight and Obese Patients With Cardiovascular Risk Factors: A Randomized Clinical Trial. JAMA. 2016 Mar 8;315(10):990-1004. doi: 10.1001/jama.2016.1558. PMID: 26954408.
  5. Partnerschap Overgewicht Nederland (PON), Zorgstandaard Obesitas. 25-11-2010. Available from: https://www.partnerschapovergewicht.nl/wp-content/uploads/2020/03/PON_Zorgstandaard_Obesitas_2011_A4_v1_04.pdf.
  6. Ross R. Is setting a criterion for 'clinically significant weight loss' necessary? Obesity (Silver Spring). 2016 Apr;24(4):791. doi: 10.1002/oby.21437. Epub 2016 Mar 1. PMID: 26929116.
  7. Williamson DA, Bray GA, Ryan DH. Is 5% weight loss a satisfactory criterion to define clinically significant weight loss? Obesity (Silver Spring). 2015 Dec;23(12):2319-20. doi: 10.1002/oby.21358. Epub 2015 Nov 2. PMID: 26523739. 
  8. Middelburg RA. Semaglutide voor gewichtsverlies bij obesitas. Gebu. 2021;55(9):89-94
  9. Productinformatie Mysimba®. Available from: https://www.geneesmiddeleninformatiebank.nl/ords/f?p=111:3::SEARCH:::P0_DOMAIN,P0_LANG,P3_RVG1:H,NL,114449. Accessed 21-07-2022.
  10. Greenway FL, Fujioka K, Plodkowski RA, Mudaliar S, Guttadauria M, Erickson J, Kim DD, Dunayevich E; COR-I Study Group. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2010 Aug 21;376(9741):595-605. doi: 10.1016/S0140-6736(10)60888-4. Epub 2010 Jul 29. Erratum in: Lancet. 2010 Aug 21;376(9741):594. Erratum in: Lancet. 2010 Oct 23;376(9750):1392. PMID: 20673995.
  11. Apovian CM, Aronne L, Rubino D, Still C, Wyatt H, Burns C, Kim D, Dunayevich E; COR-II Study Group. A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II). Obesity (Silver Spring). 2013 May;21(5):935-43. doi: 10.1002/oby.20309. PMID: 23408728; PMCID: PMC3739931.
  12. Wadden TA, Foreyt JP, Foster GD, Hill JO, Klein S, O'Neil PM, Perri MG, Pi-Sunyer FX, Rock CL, Erickson JS, Maier HN, Kim DD, Dunayevich E. Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification: the COR-BMOD trial. Obesity (Silver Spring). 2011 Jan;19(1):110-20. doi: 10.1038/oby.2010.147. Epub 2010 Jun 17. PMID: 20559296; PMCID: PMC4459776.
  13. Hollander P, Gupta AK, Plodkowski R, Greenway F, Bays H, Burns C, Klassen P, Fujioka K; COR-Diabetes Study Group. Effects of naltrexone sustained-release/bupropion sustained-release combination therapy on body weight and glycemic parameters in overweight and obese patients with type 2 diabetes. Diabetes Care. 2013 Dec;36(12):4022-9. doi: 10.2337/dc13-0234. Epub 2013 Oct 21. Erratum in: Diabetes Care. 2014 Feb;37(2):587. PMID: 24144653; PMCID: PMC3836105.
  14. Kolotkin RL, Chen S, Klassen P, Gilder K, Greenway FL. Patient-reported quality of life in a randomized placebo-controlled trial of naltrexone/bupropion for obesity. Clin Obes. 2015 Oct;5(5):237-44. doi: 10.1111/cob.12108. Epub 2015 Jul 29. PMID: 26222044.
  15. Dekkers OM. Het non-inferioriteitsonderzoek. Gebu. 2015;49(3):27-34.
  16. G-Standaard september 2022. Via KNMP Kennisbank. Accessed 01-09-2022.
  17. Van Binsbergen JJ, Langens FNM, Dapper ALM, Van Halteren MM, Glijsteen R, Cleyndert GA, Mekenkamp-Oei SN, Van Avendonk MJP. NHG-Standaard Obesitas 2010. Laatste herziening september 2020. Available from: https://richtlijnen.nhg.org/standaarden/obesitas#volledige-tekst-medicamenteuze-behandeling. Accessed 28-07-2022.

Authors

  • Marielle A.E. Nieuwhof, pharmacist