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Drug Evaluation

Naltrexone/bupropion for the treatment of obesity and obesity with Type 2 diabetes

    Caroline M Apovian

    *Author for correspondence:

    E-mail Address: caroline.apovian@bmc.org

    Boston University School of Medicine & Boston Medical Center, Boston, MA 02118, USA

    Search for more papers by this author

    Published Online:18 Dec 2015https://doi.org/10.2217/fca.15.79

    Abstract

    Contrave® is a combination of naltrexone hydrochloride extended release and bupropion hydrochloride extended release for the treatment of obesity, and is used with lifestyle modification. Its safety and efficacy were assessed in four randomized, double-blind, placebo-controlled, 56-week Phase III clinical trials in 4536 adult subjects: COR-1, COR-II, COR-BMOD and COR-DM. All four studies demonstrated statistically significant and clinically meaningful weight loss following up to 52 weeks of treatment with naltrexone/bupropion compared with placebo. The average weight loss from baseline across the four studies was approximately 11–22 lbs (5–9 kg). Results show the efficacy of Contrave for weight loss, as well as significant improvements in cardiometabolic markers. This review focuses on the four studies, their outcomes and the mechanism of action of Contrave.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

    References

    • 1 National Heart Lung, and Blood Institute, U.S. Department of Health and Human Services. What causes overweight and obesity? (2012). www.nhlbi.nih.gov/health/health-topics/topics/obe/causes#
      Google Scholar
    • 2 Apovian CM, Aronne LJ, Bessesen DH et al. Pharmacological management of obesity: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 100(2), 342–362 (2015).
      Medline CASGoogle Scholar
    • 3 Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011–2012. JAMA 311(8), 806–814 (2014).
      Medline CASGoogle Scholar
    • 4 Ogden CL, Carroll MD. Prevalence of overweight, obesity, and extreme obesity among adults: United States, trends 1960–1962 through 2007–2008, NCHS Health E-Stat, Hyattsville, MD: National Center for Health Statistics (2010). www.cdc.gov/nchs/data/hestat/obesity_adult_07_08/obesity_adult_07_08.pdf.
      Google Scholar
    • 5 Jensen MD, Ryan DH, Apovian CM et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. Circulation 129(25 Suppl. 2), S102–S138 (2014).
      MedlineGoogle Scholar
    • 6 Blackburn GL, Hutter MM, Harvey AM et al. Expert panel on weight loss surgery: executive report update. Obesity (Silver Spring) 17(5), 842–862 (2009).
      MedlineGoogle Scholar
    • 7 Fujioka K. Current and emerging medications for overweight or obesity in people with comorbidities. Diabetes Obes. Metab. 17(11), 1021–1032 (2015). • This article examines the current and emerging pharmacological options for weight management in people with overweight or obesity who have, or are at a high risk of, weight-related comorbidities.
      Medline CASGoogle Scholar
    • 8 Apovian CM, Aronne LJ, Powell AG. Clinical Management of Obesity (1st Edition). Professional Communication, West Islip, NY, USA (2015).
      Google Scholar
    • 9 Apovian CM, Garvey WT, Ryan DH. Challenging obesity: patient, provider, and expert perspectives on the roles of available and emerging nonsurgical therapies. Obesity (Silver Spring) 23(Suppl. 2), S1–S26 (2015).
      MedlineGoogle Scholar
    • 10 Kakkar AK, Dahiya N. Drug treatment of obesity: current status and future prospects. Eur. J. Intern. Med. 26(2), 89–94 (2015).
      Medline CASGoogle Scholar
    • 11 Torgerson JS, Hauptman J, Boldrin MN, Sjostrom L. XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of Type 2 diabetes in obese patients. Diabetes Care 27(1), 155–161 (2004).
      Medline CASGoogle Scholar
    • 12 Pucci A, Finer N. New medications for treatment of obesity: metabolic and cardiovascular effects. Can. J. Cardiol. 31(2), 142–152 (2015).
      MedlineGoogle Scholar
    • 13 Smith SR, Weissman NJ, Anderson CM et al. Multicenter, placebo-controlled trial of lorcaserin for weight management. N. Engl. J. Med. 363(3), 245–256 (2010).
      Medline CASGoogle Scholar
    • 14 O'Neil PM, Smith SR, Weissman NJ et al. Randomized placebo-controlled clinical trial of lorcaserin for weight loss in Type 2 diabetes mellitus: the BLOOM-DM study. Obesity (Silver Spring) 20(7), 1426–1436 (2012).
      MedlineGoogle Scholar
    • 15 Fidler MC, Sanchez M, Raether B et al. A one-year randomized trial of lorcaserin for weight loss in obese and overweight adults: the BLOSSOM trial. J. Clin. Endocrinol. Metab. 96(10), 3067–3077 (2011).
      Medline CASGoogle Scholar
    • 16 Malm-Erjefalt M, Bjornsdottir I, Vanggaard J et al. Metabolism and excretion of the once-daily human glucagon-like peptide-1 analog liraglutide in healthy male subjects and its in vitro degradation by dipeptidyl peptidase IV and neutral endopeptidase. Drug Metab. Dispos. 38(11), 1944–1953 (2010).
      Medline CASGoogle Scholar
    • 17 Wadden TA, Hollander P, Klein S et al. Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the SCALE Maintenance randomized study. Int. J. Obes. (Lond.) 37(11), 1443–1451 (2013).
      CASGoogle Scholar
    • 18 Davies MJ, Bergenstal R, Bode B et al. Efficacy of liraglutide for weight loss among patients with Type 2 diabetes: the SCALE Diabetes Randomized Clinical Trial. JAMA 314(7), 687–699 (2015).
      Medline CASGoogle Scholar
    • 19 Astrup A, Carraro R, Finer N et al. Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide. Int. J. Obes. (Lond.) 36(6), 843–854 (2012).
      CASGoogle Scholar
    • 20 Yanovski SZ, Yanovski JA. Naltrexone extended-release plus bupropion extended-release for treatment of obesity. JAMA 313(12), 1213–1214 (2015).
      Medline CASGoogle Scholar
    • 21 Caixas A, Albert L, Capel I, Rigla M. Naltrexone sustained-release/bupropion sustained-release for the management of obesity: review of the data to date. Drug Des. Devel. Ther. 8, 1419–1427 (2014).
      Medline CASGoogle Scholar
    • 22 Mercer SL. ACS chemical neuroscience molecule spotlight on contrave. ACS Chem. Neurosci. 2(9), 484–486 (2011).
      Medline CASGoogle Scholar
    • 23 Naltrexone/bupropion: Contrave®; naltrexone SR/bupropion SR. Drugs R D 10(1), 25–32 (2010).
      MedlineGoogle Scholar
    • 24 Nuzzaci D, Laderriere A, Lemoine A et al. Plasticity of the melanocortin system: determinants and possible consequences on food intake. Front. Endocrinol. (Lausanne) 6, 143 (2015). • The melanocortin system is one of the most important neuronal pathways involved in the regulation of food intake. AgRP and POMC-expressing neurons located in the arcuate nucleus of the hypothalamus are the key elements of this system.
      MedlineGoogle Scholar
    • 25 Roseberry AG, Stuhrman K, Dunigan AI. Regulation of the mesocorticolimbic and mesostriatal dopamine systems by alpha-melanocyte stimulating hormone and agouti-related protein. Neurosci. Biobehav. Rev. 56, 15–25 (2015).
      Medline CASGoogle Scholar
    • 26 Aponte Y, Atasoy D, Sternson SM. AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training. Nat. Neurosci. 14(3), 351–355 (2011).
      Medline CASGoogle Scholar
    • 27 Krashes MJ, Koda S, Ye C et al. Rapid, reversible activation of AgRP neurons drives feeding behavior in mice. J. Clin. Invest. 121(4), 1424–1428 (2011).
      Medline CASGoogle Scholar
    • 28 Billes SK, Sinnayah P, Cowley MA. Naltrexone/bupropion for obesity: an investigational combination pharmacotherapy for weight loss. Pharmacol. Res. 84, 1–11 (2014).
      Medline CASGoogle Scholar
    • 29 Wang GJ, Tomasi D, Volkow ND et al. Effect of combined naltrexone and bupropion therapy on the brain's reactivity to food cues. Int. J. Obes. (Lond.) 38(5), 682–688 (2014).
      CASGoogle Scholar
    • 30 Greenway FL, Fujioka K, Plodkowski RA et al. 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 376(9741), 595–605 (2010). •• Mean change in bodyweight was -1.3% (SE 0.3) in the placebo group, -6.1% (0.3) in the naltrexone 32 mg plus bupropion group (p < 0.0001 vs placebo) and -5.0% (0.3) in the naltrexone 16 mg plus bupropion group (p < 0.0001 vs placebo).
      Medline CASGoogle Scholar
    • 31 Apovian CM, Aronne L, Rubino D et al. A randomized, Phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II). Obesity (Silver Spring) 21(5), 935–943 (2013). •• Significantly (p < 0.001) greater weight loss was observed with NB32 versus placebo at week 28 (-6.5 vs -1.9%) and week 56 (-6.4 vs -1.2%).
      Medline CASGoogle Scholar
    • 32 Wadden TA, Foreyt JP, Foster GD et al. Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification: the COR-BMOD trial. Obesity (Silver Spring) 19(1), 110–120 (2011). •• At week 56, weight loss was 5.1 +/- 0.6% with placebo + behavior modification (BMOD) vs 9.3 +/- 0.4% with NB32 + BMOD (p < 0.001).
      Medline CASGoogle Scholar
    • 33 Hollander P, Gupta AK, Plodkowski R et al. 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 36(12), 4022–4029 (2013). •• Naltrexone/bupropion (NB) resulted in significantly greater weight reduction (-5.0 vs -1.8%; p < 0.001) and proportion of patients achieving >/=5% weight loss (44.5 vs 18.9%, p < 0.001) compared with placebo. NB also resulted in significantly greater HbA1c reduction (-0.6 vs -0.1% [6.6 vs 1.1 mmol/mol]; p < 0.001), percent of patients achieving HbA1c <7% (53 mmol/mol) (44.1 vs 26.3%; p < 0.001), and improvement in triglycerides and HDL cholesterol compared with placebo.
      Medline CASGoogle Scholar
    • 34 Greig SL, Keating GM. Naltrexone ER/Bupropion ER: a review in obesity management. Drugs 75(11), 1269–1280 (2015).
      Medline CASGoogle Scholar
    • 35 Bragg R, Crannage E. Review of pharmacotherapy options for the management of obesity. J. Am. Assoc. Nurse Pract. doi:10.1002/2327-6924.12279 (2015) (Epub ahead of print).
      MedlineGoogle Scholar
    • 36 Takeda Pharmaceuticals America I. Contrave (package insert). Takeda Pharmaceuticals America, Inc., Deerfield, IL (2014).
      Google Scholar
    • 37 Verpeut JL, Bello NT. Drug safety evaluation of naltrexone/bupropion for the treatment of obesity. Expert Opin. Drug. Saf. 13(6), 831–841 (2014).
      Medline CASGoogle Scholar
    • 38 Lofti K, Palmer K, Apovian CM. Case study: weight loss in a patient with Type 2 diabetes: challenges of diabetes management. Obesity (Silver Spring) 23(Suppl. 1), S11–S12 (2015).
      MedlineGoogle Scholar