The identification of potential treatment targets to reduce the risk of obesity‐related complications: a step toward a treat‐to‐target approach in obesity management

  • Luca Busetto*
  • , Volker Schnecke
  • , Maria Overvad
  • , Silvia Capucci
  • , Ricardo Reynoso
  • , Rafael Bravo
  • , Abd A. Tahrani
  • , Camilla S. Morgen
  • *Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Aims: Obesity‐related complications (ORCs) are associated with substantial health and economic burdens. Although treatment targets are routinely used for other chronic conditions, none currently exist in obesity management. We aimed to identify an adiposity measure that indicates a reduced risk of four ORCs.

Materials and Methods: This population‐based cohort study of patients aged 18–60 years used data from the UK Clinical Practice Research Datalink Aurum. Associations between absolute 10‐year ORC risk and baseline body mass index (BMI), waist–height ratio (WHtR), and changes in adiposity measures after weight loss were calculated. Absolute values and changes in adiposity measures were evaluated as a proxy for achieving an absolute 10‐year ORC risk similar to that of people without obesity, and optimal cut‐offs were identified based on the balance between true positive and true negative rates for achieving the treatment goal.

Results: Absolute values of BMI and WHtR post‐weight change were more strongly associated with 10‐year ORC risk than relative changes; WHtR was the best proxy for a low absolute risk for type 2 diabetes, hypertension, and atherosclerotic cardiovascular disease, and BMI for hip/knee osteoarthritis. Based on the balance between true negative and true positive rates of multiple cut‐offs, a BMI ≤ 27 kg/m2 and WHtR ≤ 0.53 are proposed as potential treatment targets for obesity.

Conclusions: These findings suggest that treatment goals for obesity management may be considered on post–weight‐change absolute adiposity measures, rather than relative changes. Both weight and WHtR may be considered when defining treatment targets for ORC risk reduction.
Original languageEnglish
Article numbere70094
Number of pages11
JournalObesity Science & Practice
Volume11
Issue number6
Early online date5 Nov 2025
DOIs
Publication statusPublished - Dec 2025

Keywords

  • cohort study
  • observational
  • primary care
  • obesity care
  • database research

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