title: Health-related quality of life in two randomized controlled trials of phentermine/topiramate for obesity: What mediates improvement?
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Community and Family Medicine, Duke University School of Medicine, Durham, NC, USA. rkolotkin@qualityoflifeconsulting.com.|Quality of Life Consulting, 732 Ninth Street #563, Durham, NC, 27705, USA. rkolotkin@qualityoflifeconsulting.com.|Department of Health Studies, Sogn og Fjordane University College, Førde, Norway. rkolotkin@qualityoflifeconsulting.com.|Morbid Obesity Centre, Vestfold Hospital Trust, Tønsberg, Norway. rkolotkin@qualityoflifeconsulting.com.
authors.forename: Ronette L
authors.initials: RL
authors.lastname: Kolotkin
authors.affiliation: Pennington Biomedical Research Centre, Baton Rouge, LA, USA.
authors.forename: Kishore M
authors.initials: KM
authors.lastname: Gadde
authors.affiliation: VIVUS, Inc., Mountain View, CA, USA.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Peterson
authors.affiliation: Neuropsychiatric Research Institute, Fargo, ND, USA.|Department of Psychiatry and Behavioral Science, University of North Dakota School of Medicine and Health Sciences, Fargo, ND, USA.
authors.forename: Ross D
authors.initials: RD
authors.lastname: Crosby
mesh_terms: D000328:Adult; D015992:Body Mass Index; D001835:Body Weight; D003863:Depression / Q000188:drug therapy*; D005260:Female; D005632:Fructose / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006304:Health Status; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy* / Q000523:psychology; D017063:Outcome Assessment, Health Care; D010645:Phentermine / Q000627:therapeutic use*; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D011795:Surveys and Questionnaires; D000077236:Topiramate; D015431:Weight Loss / Q000187:drug effects*
chemical_list: D000077236:Topiramate; D005632:Fructose; D010645:Phentermine
keywords: Health-related quality of life; Impact of Weight on Quality of Life-Lite (IWQOL-Lite); Mediation analysis; Phentermine/topiramate; Short-Form-36 (SF-36); Weight loss