Incretin-Based Therapy in Patients with Malignancy and Obesity or Type 2 Diabetes. An Italian Association of Medical Oncology (AIOM), Italian Association of Medical Diabetologists (AMD), Italian Society of Diabetology (SID), Italian Society of Endocrinology (SIE), Italian Society of Pharmacology (SIF), and Italian Society of Obesity (SIO) Position Paper.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as pivotal agents in the treatment of type 2 diabetes (T2D) and obesity, with well-established metabolic and cardiovascular benefits that translate into improvement in quality of life and life expectancy. While a potential benefit may also be hypothesized in patients with metabolic disorders and malignancy, robust clinical evidence is still lacking. In recent years, attention has turned to their potential impact on cancer risk, although current evidence remains limited and, in some cases, conflicting. Several biological pathways, such as improvements in insulin sensitivity, reductions in chronic inflammation, modulation of cellular signaling, and changes in the tumor microenvironment, have been proposed as possible mechanisms through which GLP-1RAs might influence cancer development or progression. However, available data derive from preclinical or observational studies, and high-quality prospective clinical evidence is still lacking. While some reports suggest possible protective associations in specific cancer types, others raise concerns about potential risks, particularly in hormonally sensitive or receptor-expressing tissues. This position paper synthesizes available data on the oncologic safety and potential antitumor effects of GLP-1RAs, highlights key knowledge gaps, and discusses clinical implications, underscoring the need for further research to clarify their role in cancer prevention and treatment.