Health-related quality of life in two randomized controlled trials of phentermine/topiramate for obesity: What mediates improvement?
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Phentermine/topiramate combination therapy resulted in significant weight loss and improvements in cardiometabolic risk factors in patients with obesity/overweight in two published 56-week randomized, placebo-controlled trials (EQUIP and CONQUER). The purpose of the current study was to examine whether phentermine/topiramate is also associated with greater improvements in health-related quality of life (HRQOL) and whether HRQOL improvements are solely attributable to weight reduction.
Patients in EQUIP (n = 751) had a body mass index (BMI) ≥ 35 with no obesity-related comorbidity. Patients in CONQUER (n = 1623) had a BMI ≥ 27 and ≤ 45 and at least two obesity-related comorbid conditions. HRQOL was assessed with Impact of Weight on Quality of Life-Lite (IWQOL-Lite) and Medical Outcomes Study Short Form (SF-36) (CONQUER only).
Significant improvements in both obesity-specific and physical HRQOL were observed at 56 weeks in both trials (p < .0001). In EQUIP, BMI reduction fully mediated improvements in IWQOL-Lite total score (p < .0001). In CONQUER, both BMI reduction (all p values <.0001) and change in depressive symptoms (all p values <.025) were significant mediators of improved IWQOL-Lite total score and SF-36 Physical Component Summary score. Gender, psychiatric history, and baseline triglycerides moderated these relationships.
Both trials demonstrated that treatment with phentermine/topiramate improved HRQOL compared with placebo. Although reduction in BMI accounted for the majority of improvements in obesity-specific and physical HRQOL, decrease in depressive symptoms was also a significant mediator. Results highlight the predominance of weight reduction as a key factor in improving HRQOL in obesity.
KeywordsHealth-related quality of life Phentermine/topiramate Weight loss Mediation analysis Impact of Weight on Quality of Life-Lite (IWQOL-Lite) Short-Form-36 (SF-36)
Vivus was the sponsor of the two trials (EQUIP and CONQUER) upon which the current study was based.
Compliance with ethical standards
Conflict of interest
Authors R.L.K. and R.D.C. received consulting fees from Vivus, the sponsor of the trials. K.M.G. was the principal investigator for the trial. C.A.P. is an employee of Vivus. R.L.K. received royalties from Duke University for the use of the IWQOL-Lite.
- 1.Gadde, K. M., Allison, D. B., Ryan, D. H., Peterson, C. A., Troupin, B., Schwiers, M. L., et al. (2011). Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): A randomised, placebo-controlled, phase 3 trial. Lancet, 377(9774), 1341–1352.CrossRefPubMedGoogle Scholar
- 3.Fujioka, K., Seaton, T. B., Rowe, E., Jelinek, C. A., Raskin, P., Lebovitz, H. E., et al. (2000). Weight loss with sibutramine improves glycaemic control and other metabolic parameters in obese patients with type 2 diabetes mellitus. Diabetes, Obesity & Metabolism, 2(3), 175–187.CrossRefGoogle Scholar
- 9.Hayes, A. F. (2013). Introduction to mediation, moderation, and conditional process analysis : A regression-based approach. In. NY: Guilford Press.Google Scholar
- 13.Ware, J. E., Snow, K. K., Kosinski, M., & Gandek, B. (1993). SF-36 health survey: Manual and interpretation guide. Boston: Health Institute, New England Medical Center.Google Scholar
- 18.Wee, C. C., Davis, R. B., Huskey, K. W., Jones, D. B., & Hamel, M. B. (2013). Quality of life among obese patients seeking weight loss surgery: The importance of obesity-related social stigma and functional status. Journal of General Internal Medicine, 28(2), 231–238.CrossRefPubMedPubMedCentralGoogle Scholar
- 19.Astrup, A., Madsbad, S., Breum, L., Jensen, T. J., Kroustrup, J. P., & Larsen, T. M. (2008). Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: A randomised, double-blind, placebo-controlled trial. Lancet, 372(9653), 1906–1913.CrossRefPubMedGoogle Scholar
- 23.Brandão, I., Ramalho, S., Pinto-Bastos, A., Arrojado, F., Faria, G., Calhau, C., et al. (2015). Metabolic profile and psychological variables after bariatric surgery: Association with weight outcomes. Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity, 1–6. doi: 10.1007/s40519-015-0199-7.
- 29.Williamson, D. A., Rejeski, J., Lang, W., Van Dorsten, B., Fabricatore, A. N., & Toledo, K. (2009). Impact of a weight management program on health-related quality of life in overweight adults with type 2 diabetes. Archives of Internal Medicine, 169(2), 163–171.CrossRefPubMedPubMedCentralGoogle Scholar
- 30.Palmeira, A. L., Markland, D. A., Silva, M. N., Branco, T. L., Martins, S. C., Minderico, C. S., et al. (2009). Reciprocal effects among changes in weight, body image, and other psychological factors during behavioral obesity treatment: A mediation analysis. The International Journal of Behavioral Nutrition and Physical Activity, 6, 9.CrossRefPubMedPubMedCentralGoogle Scholar
- 37.Rothberg, A. E., McEwen, L. N., Kraftson, A. T., Neshewat, G. M., Fowler, C. E., Burant, C. F., et al. (2014). The Impact of Weight Loss on Health-Related Quality-of-Life: Implications for cost-effectiveness analyses. Quality of Life Research, 23(4), 1371–1376.CrossRefPubMedPubMedCentralGoogle Scholar