Health-related quality of life in two randomized controlled trials of phentermine/topiramate for obesity: What mediates improvement?

Qual Life Res. 2016 May;25(5):1237-44. doi: 10.1007/s11136-015-1153-x. Epub 2015 Oct 7.


Purpose: 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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Body Mass Index
  • Body Weight
  • Depression / drug therapy*
  • Female
  • Fructose / analogs & derivatives*
  • Fructose / therapeutic use
  • Health Status*
  • Humans
  • Male
  • Middle Aged
  • Obesity / drug therapy*
  • Obesity / psychology
  • Outcome Assessment, Health Care
  • Phentermine / therapeutic use*
  • Quality of Life*
  • Randomized Controlled Trials as Topic
  • Surveys and Questionnaires
  • Topiramate
  • Weight Loss / drug effects*


  • Topiramate
  • Fructose
  • Phentermine