AACR report finds mixed evidence on GLP-1 drugs and cancer risk

The American Association for Cancer Research's 2026 Cancer Progress Report states that evidence linking GLP-1 medications to reduced cancer risk is mixed, with randomized clinical trials for cancer outcomes yet to be conducted. The report identifies obesity as a major risk factor for many cancers, a condition that glucagon-like peptide-1 drugs, including semaglutides like Ozempic and Wegovy, and tirzepatides like Mounjaro and Zepbound, are known to treat through substantial weight loss and metabolic improvement.

Sai Yendamuri, a thoracic surgeon at Roswell Park Comprehensive Cancer Center in Buffalo, New York, noted that obesity is a leading cause of cancer, second only to smoking. He explained that other risk factors, such as alcohol and poor nutrition, are often layered into obesity. Yendamuri, who was not associated with the AACR report, suggested that if obesity drives cancer progression, a drug that decreases obesity might have an impact. He pointed to studies of metabolic surgery showing decreased cancer incidence in patients who lost weight.

Researchers have compared cancer incidence in patients taking GLP-1 receptor agonists against those not taking them. Many of these studies found lower cancer risk and higher survival rates among patients using the medications. However, Yendamuri noted that some studies found no relationship, and a couple showed an increased risk for specific cancers, such as thyroid cancer. He attributed this disconnect to the retrospective nature of the studies, which derive associations from existing data while lacking control over other variables.

Yendamuri's own team has investigated the link between obesity and lung cancer. He stated that every investigation conducted by his team found that obesity increases the risk of lung cancer. The research also examined how obesity is measured, noting a shift away from relying solely on body mass index toward more precise assessments of body fat composition.

Two key findings from Yendamuri's research suggest potential benefits for patients on GLP-1 receptor agonists. First, patients undergoing lung cancer resection while on these drugs appeared to have lower recurrence rates. Second, patients with advanced-stage cancers receiving immunotherapy and taking GLP-1s also had lower recurrence rates. Based on preclinical laboratory studies, Yendamuri believes these medications have only a limited direct effect on cancer cells.

Instead, Yendamuri proposed that the drugs change the body's immune response to cancer cells, improving the body's ability to fight them. He noted that this effect may vary by cancer type because the immune response is more critical in some diseases than others. For example, in melanoma, the immune response is considered incredibly important. Yendamuri acknowledged that at least some of the cancer benefit likely stems from weight loss itself.

He highlighted that not every patient taking GLP-1 receptor agonists responds with substantial weight loss. Future trials would need to determine if the cancer benefit depends on weight loss by comparing outcomes between patients who lose weight and those who do not. Yendamuri expressed hope that GLP-1 drugs could eventually be regarded as a preventive mechanism for cancer. He emphasized that lifestyle modifications, including exercise, weight decrease, and GLP-1 receptor agonists, will likely play a role in enhancing cancer treatment and preventing second cancers.

Yendamuri concluded by emphasizing the importance of continued funding for the National Cancer Institute to support researchers advancing cancer research and developing new discoveries.