Appetite, Obesity, Metabolism, and Malignancy: Do Incretin-Mimetic Drugs Reduce Cancer Risk?

Obesity is associated with increased risk of at least 13 adult cancer types and is the second most common cause of cancer (after tobacco) in many populations. Uncertainty about the extent to which intentional weight loss leads to reduced cancer risk represents a gap in knowledge. Evidence from bariatric surgery studies shows that sustained weight reduction of 20% to 30% in individuals with severe obesity is associated with reduced risk of obesity-related cancers over 10 years. However, in terms of population health, this is not a viable cancer prevention strategy. Recently, glucagon-like peptide-1 receptor agonists (GLP-1RA), known to be effective antidiabetes drugs, have been shown in randomized trials to cause substantial weight loss (in the order of 15%) in obese individuals with or without diabetes. This is a rapidly evolving field, which has revolutionized the modern management of obesity. Much clinical experience has been with semaglutide (a GLP-1RA) and tirzepatide (a dual agonist of the GLP-1 receptor and the glucose-dependent insulinotropic polypeptide receptor), but newer drugs in the class are being developed. We review available data that provide a strong rationale for evaluating incretin-mimetic drugs in a cancer prevention trial but show that the feasibility of such a trial is questionable.