Preventing obesity-related cancer with the revolution in obesity management: the challenges of undertaking a clinical trial and potential solutions.

This publication is a perspective piece examining whether modern anti-obesity pharmacotherapy—particularly GLP‑1 receptor agonists and related dual/triple agonists—could meaningfully reduce obesity‑related cancer risk, and how to generate robust evidence for this.

Key points:

• Existing evidence:
  • Conventional epidemiology and Mendelian randomisation strongly support a causal link between obesity and increased risk of several common cancers.
  • Quasi‑experimental data from bariatric surgery show that substantial, sustained weight loss is associated with lower cancer incidence, especially in women.
  • Despite this, there are no major public health strategies specifically focused on weight management for cancer prevention.
• Barriers to cancer prevention via obesity control:
  • Limited public and professional awareness of the causal obesity–cancer connection.
  • Lifestyle interventions typically yield modest weight loss that is rarely durable enough to meaningfully affect long‑term cancer risk.
• New context: GLP‑1–based pharmacotherapy:
  • GLP‑1 agonists and newer dual/triple agonists now produce large, sustained weight loss while treatment continues.
  • This creates a new, central research question: can long‑term use of these agents significantly reduce the incidence of obesity‑related cancers?
• Trial and research design considerations:
  • Direct randomized cancer‑endpoint trials would require very large sample sizes, long follow‑up, and substantial cost, posing major logistical challenges.
  • The authors discuss potential strategies to address this, including:
    • Alternative trial designs and endpoints.
    • Use of existing or new large cohorts and registries.
    • Quasi‑experimental and pharmacoepidemiologic approaches that leverage real‑world use of GLP‑1–based agents.

Overall, the article frames GLP‑1 and related anti‑obesity drugs as a major opportunity for cancer prevention research and outlines the practical hurdles and design options needed to determine whether these agents truly lower cancer risk.