Objective: This study examined (1) the association between weight loss and changes in health-related quality of life (HRQoL) and (2) treatment response heterogeneity among patients in a weight loss intervention.
Methods: Eighteen primary care clinics were randomized to a 24-month intensive lifestyle intervention or usual care. Generic HRQoL and weight-related QoL were assessed at baseline and months 6, 12, and 24. Associations were analyzed using repeated-measures linear multilevel models.
Results: The sample included 803 patients with obesity. Changes in generic HRQoL did not differ by race or sex, and weight-related QoL did not differ by sex. However, Black patients experienced less improvement in weight-related QoL compared to other races. There was a graded association between improvements in weight-related QoL and greater weight loss between baseline and 24 months: 7.4 (95% CI: 5.1, 9.7) for those who lost < 5% of their initial body weight, 15.0 (11.4, 18.5) for 5% to < 10% weight loss, and 18.9 (15.4, 22.4) for ≥ 10% weight loss. Greater weight loss was also related to greater improvements in most generic HRQoL domains.
Conclusions: Weight loss was associated with improvements in HRQoL, and race differences were identified in changes in weight-related QoL, highlighting the need for precision medicine approaches to weight loss.
Trial registration: ClinicalTrials.gov identifier NCT02561221.
Keywords: patient‐reported outcomes; treatment effect heterogeneity; well‐being.
© 2026 The Obesity Society.