Researchers warn that GLP-1RA medications may not be the magic bullet we’re looking for when it comes to cancer

The rapid rise of adults taking GLP-1RA medications (e.g., Wegovy, Ozempic, Mounjaro) in the U.S. (16 million and counting) and around the world has been accompanied by a slew of the drugs’ proclaimed health benefits. Weight loss is a common (and extremely popular) side effect, making GLP-1RAs some of the most exciting weapons in the arsenal for battling the obesity epidemic. Loss of unhealthy visceral fat and improved blood sugar control are just two of the downstream effects of this weight loss, which, in turn, promise their own health benefits.

But what do we really know about the long-term impacts of GLP-1RA medications? Researchers caution us not to get ahead of ourselves when it comes to the logical, though still theoretical, possibilities of how these drugs may influence related health conditions such as cancer. 

“Short-term research has shown that GLP-1RAs result in substantial weight loss and accompanying metabolic benefits such a reduction in visceral adipose tissue – the hard-to-lose fat that attaches to our organs – improved insulin sensitivity, and lower systemic inflammation,” says Health Sciences Distinguished Professor James Hébert, a cancer epidemiologist and inflammation expert who has published nearly a thousand peer-reviewed journal articles. “It stands to reason that these improved health markers would lead to a reduced risk in the more than 13 obesity-related cancers, but it’s just too soon to make that claim.”

Hébert and other cancer experts from the Arnold School’s Department of Exercise Science, USC School of Medicine Columbia and College of Pharmacy, University of Utah, and University of Tennessee recently published a paper in the Nature Reviews Cancer to weigh in on the debate.

A number of scientists have reviewed previous studies involving patients with type 2 diabetes – predicting that the effects of GLP-1RAs might lead to a reduction in the risk of obesity-related cancers such as hepatocellular, endometrial, colorectal and kidney. But Hébert and his co-authors caution that the conclusions drawn from these meta-analyses overlook two important factors. First, they point out, these types of cancers generally take a long time to develop. And, second, the widespread (i.e., population-level) use of GLP-1RAs for weight loss is very recent.

The unknown intermediate and long-term side effects of these drugs is concerning, but so are the known risks. Skeletal muscle atrophy/loss, for example, is a common side effect for individuals who experience significant weight loss but who do not engage in the parallel physical activity required to support muscle retention. Loss of skeletal muscle mass actually undermines blood sugar control and increases cancer susceptibility. The nutrient deficiencies that may result from GLP-1RA-induced appetite suppression also pose increased cancer risks.

Another concern? The rebound effect of discontinuing the medication. Individuals who stop taking GLP-1RAs are not only likely to return to a state of visceral fat re-accumulation, insulin resistance, and widespread, systemic and tissue-specific simmering inflammation (e.g., knee osteoarthritis), they could face additional challenges (e.g., complex hormonal shifts, disruptions to neurological signals related to appetite cues) that increase their risk of cancer beyond their baseline level of risk before taking GLP-1RAs. Further, inconsistent insurance coverage can impact the availability and continuity of these prescriptions, putting low-resource populations at increased risk for possible rebound effects.  

The way forward is twofold.

Well-designed clinical trials are a must, the authors state. These studies must evaluate short-, intermediate-, and long-term cancer risk biomarkers. Further, epidemiological datasets must be leveraged to clarify the associations between the medications and health outcomes as well as track long-term cancer incidence and mortality.

In addition to these studies, the authors suggest that clinicians prescribe dietary and physical activity recommendations alongside GLP-1RAs. Not only will this guidance help mitigate muscle loss, but it also helps address the drivers of both obesity and cancer (e.g., poor diet, sedentary lifestyles). Relying solely on GLP1-RAs also ignores additional drivers, such as environmental exposures and genetic factors, that should also be addressed but may be ignored if attempting a “magic bullet” solution.

“The rise of GLP-1RA medications presents a powerful obesity intervention with potential for obesity-related cancer prevention,” Hébert says. “Yet, rapid adoption for obesity treatment may outpace our understanding of the potential consequences for long-term cancer risk.”