William G. Nelson, MD, PhD Photo by Joe Rubino

THE CENTERS FOR DISEASE CONTROL AND PREVENTION estimates that nearly 42% of U.S. adults are obese, up from 30% at the dawn of the new millennium. By 2030, the global burden of obesity will climb to more than a billion adults.

Obesity likely contributes to poorer outcomes for patients with cancers of the breast, prostate, colon and rectum, uterus, liver, kidney and pancreas. It is responsible for as much as a 17% increased risk of cancer mortality. Could the growing number of drugs available for obesity treatment reduce cancer deaths?

The relationships between obesity and cancer are varied and complex. Body fat deposits lie within adipose tissues under the skin, in and around internal organs, and in many other locations like bone marrow, breast tissue, eye sockets and other sites. Together, the distributed adipose tissues act like an independent organ—storing and releasing energy, releasing and responding to hormone signals, and regulating appetite and satiety, the feeling of fullness.

When there is too much need for fat storage, the existing fat cells grow larger, leading to chronic inflammation and to insulin insensitivity with poor glucose control, both conditions tending to promote cancer growth and progression. Fat cells also produce estrogenic hormones, which can contribute to cancers of the breast and uterus. In addition, the bacteria residing in the intestines, referred to as the microbiome, tend to be altered in the setting of obesity, which can impact cancer development and treatment.

Apart from cancer, there are countless health benefits to weight loss in the setting of obesity. Yet, despite a strong motivation to lose weight, most self-directed attempts at weight reduction are unsuccessful. Coach-directed weight loss tactics perform better, with more than half of obese adults able to lose 5% or more of their initial weight, though rebound weight gain is common. Weight-reduction surgery can deliver 25% or greater weight loss, with most people regaining at least 5% to 10% of their lowest weight over the decade or so following surgery.

More recently, there has been an explosion of drugs now available or under active development for treating obesity. This new wave of drug discovery has focused on agents that mimic the actions of glucagon-like peptide-1 (GLP-1), a short-lived hormone that enhances insulin secretion (helping to control blood sugar in people with diabetes), delays stomach emptying and promotes a sense of satiety that limits food intake. The GLP-1-like drugs persist longer in the body than GLP-1 itself, enabling these agents to improve blood sugar control for diabetes and to promote weight loss.

Since the first GLP-1-like drug, semaglutide (with brand names Ozempic, Wegovy and Rybelsus), was approved by the Food and Drug Administration, eight additional GLP-1-like drugs have been introduced into clinical trials. As of January 2024, there were 369 ongoing clinical studies of these agents—mostly for diabetes and related complications. Already, semaglutide (as Wegovy), liraglutide (as Saxenda) and tirzepatide (as Zepbound) have been approved for weight loss in the absence of diabetes and are able to effect as much as a 5% to 15% weight reduction in the obesity setting. Adoption of these drugs has been astonishing: A recent report suggests that more than 9 million prescriptions for Ozempic, Wegovy and similar drugs were filled in the last three months of 2022.

What will GLP-1-like drugs do for cancer control? There have been worries that the agents might increase the risk of cancer, particularly of thyroid cancers and pancreatic cancer. Thus far, use of these drugs does appear to increase thyroid cancer risk but not the risk of pancreatic cancer, though more real-world evidence needs to be collected and reviewed. On the other hand, the use of GLP-1-like drugs for diabetes treatment may decrease colorectal cancer risk by as much as 44%, much greater than other diabetes drugs. Tantalizing risk reductions have also been seen for prostate cancer.

The incredibly rapid adoption of GLP-1-like drugs for weight loss calls for carefully designed clinical trials to ascertain effects of these agents on the risk of developing cancer, on the efficacy of cancer treatment, and on improving the health of cancer survivors. Hopefully, when used along with diet changes and exercise, the GLP-1-like drugs will be able to safely reverse the ongoing epidemic of obesity and limit the deleterious impact of obesity on cancer.

William G. Nelson, MD, PhD, is the director of the Johns Hopkins Kimmel Cancer Center in Baltimore.