What Impact Will GLP-1 Agonists Have on Cancer?

John M. Burke, MD

Hematologist and Medical Oncologist

Rocky Mountain Cancer Centers

Associate Chair

US Oncology Hematology Research Program

Aurora, CO

The prevalence of obesity, defined as a body mass index (BMI) greater than 30 kg/m², and overweight, defined as a BMI of 25-29.9 kg/m², in the US has increased over time. Estimates are that 42% of American adults are obese,¹ and projections have estimated that, by the year 2030, nearly half of American adults may have obesity.² Among the many adverse health consequences of obesity is an increased risk of 13 cancers: endometrial, kidney, gastric, colon, rectal, biliary tract, pancreas, breast, esophageal, ovarian, multiple myeloma, hepatocellular, and meningioma.³

Drug therapy to treat obesity has improved. Development of glucagon-like peptide 1 (GLP-1) agonists semaglutide (Wegovy, Ozempic) and liraglutide (Saxenda), and the glucose-dependent insulinotropic polypeptide/GLP-1 dual receptor agonist tirzepatide (Mounjaro), has been the key driver in the increased use of the drug. According to a recent Kaiser Family Foundation (KFF) health tracking poll, 6% of American adults are currently taking GLP-1 agonists, and 12% have taken them at some point.⁴ In addition, these drugs are improving blood sugar control in diabetes, cardiovascular outcomes, reduction in steatohepatitis and liver fibrosis and in the severity of sleep apnea.

Wang et al attempted to understand how the impact of these agents will effect the incidence of cancer in a paper published in JAMA Network Open.⁵ The authors used electronic health records to identify more than 1.6 million patients with type 2 diabetes mellitus, and found that, compared with insulins, GLP-1 receptor agonists were associated with a significant reduction in the risk of 10 of the 13 obesity-associated cancers, with the 3 exceptions being gastric, postmenopausal breast, and thyroid. Previous studies evaluating other methods of achieving weight loss have shown reduction in the incidence of obesity-associated cancers. However, other methods of weight loss, such as intensive lifestyle intervention and bariatric surgery, may not have the potential to impact as many people as GLP-1 agonists. One aberration in the study was that use of GLP-1 agonists was associated with a higher risk of kidney cancer vs metformin.

Despite this retrospective study, and the associated limitations, the study creates optimism that suggests that addressing obesity in the US will reduce the cancer burden in our society.