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

Evidence from conventional and Mendelian Randomisation epidemiological studies support the conclusion that obesity is causally associated with increased risk of several common cancer types. Some evidence, notably from quasi-experimental bariatric surgery studies, support the concept that sustained long-term weight loss in individuals is associated with reduction of cancer incidence, particularly in women. Yet, there are no authoritative public health policies directed specifically at large-scale weight management interventions to prevent obesity-related cancers. At least two adversities conspire against public health success: (i) awareness of the causal link between obesity and cancer risk; and (ii) lifestyle interventions are associated with only moderate weight loss that is generally not sustained long enough to result in clinically meaningful cancer prevention. However, there is now a revolution of effective pharmacotherapy for obesity, namely glucagon-like-peptide (GLP)-1 agonists and their extended family of dual and triple agonists, which leads to substantial rates of weight loss, sustained while individuals continue to take the drug. There is now a key new cancer prevention research question, whether this drug class might significantly reduce cancer risk with long-term use. The logistics of addressing this question in a clinical trial setting are discussed and potential strategies to overcome these challenges are proposed.