CHICAGO—At the world’s largest oncology conference, Ozempic, a diabetes drug, found its way to the center of the conversation. As thousands of attendees bounced between presentations at the American Society of Clinical Oncology (ASCO) meeting, some of the biggest buzz focused on the connection between taking Ozempic and similar glucagonlike peptide 1 (GLP-1) receptor agonists and having a decreased risk of several types of cancer.
GLP-1 drugs, originally designed to treat type 2 diabetes, have become blockbuster treatments for weight loss and metabolic conditions such as heart, liver and kidney disease. Now researchers are investigating whether certain cancers, such as breast cancer, could be added to that list. At the conference, scientists announced their findings that people taking GLP-1 drugs were less likely to be diagnosed with certain cancers, have them spread or die from them when compared with nonusers and those on other diabetes medications. Even though the findings are largely based on observational studies, they reinforce animal research that shows GLP-1 drugs do more than just shed pounds and improve metabolic health. The drugs may also dial down the inflammation that can drive cancer development—and might even act directly on tumors.
Obesity has long been identified as a risk factor for at least 13 types of cancer. Excess weight promotes chronic inflammation, raises insulin levels in the blood and increases estrogen circulating in the body—all potential drivers of cancer development. Whether GLP-1 treatments reduce cancer risk by reversing these pathways through weight loss, or through some other mechanism entirely, remains an open question. Several lines of research presented at ASCO offer evidence of the drugs’ protective effect against cancer, including several not typically associated with weight, such as leukemia and lung cancer, says Elizabeth McDonald, radiologist at the Hospital of the University of Pennsylvania.
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McDonald’s team at the University of Pennsylvania found GLP-1 drugs were linked to a 30 percent lower likelihood of a breast cancer diagnosis in more than 111,000 women who underwent breast imaging. Another large analysis from the Virginia Commonwealth University (VCU) Massey Comprehensive Cancer Center, published in JAMA Network Open before the conference, followed breast cancer patients for up to 10 years and found that those who took GLP-1s had a lower risk of death from any cause—and a reduced risk of cancer recurrence—compared with patients who did not take them. And in another investigation, co-led by researchers at Massey, found that GLP-1 drugs were associated with improved survival among people with colorectal cancer as well. A Cleveland Clinic study tracking people across seven cancer types found that those taking the drugs were significantly less likely to progress to stage four disease in lung, breast, colorectal and liver cancers—with a 43 percent risk reduction seen in breast cancer and a 50 percent reduction in lung cancer.
These studies collectively provide an “interesting signal,” says Jasmine Sukumar, a breast medical oncologist at the University of Texas MD Anderson Cancer Center, who also presented research on GLP-1s’ protective effect against breast cancer. The data are still observational, which means the research teams cannot prove cause and effect, she adds. Still, Sukumar and other scientists are trying to understand what might be driving these findings.
The most straightforward explanation is the weight loss that the drugs can cause. Reducing weight also reduces the pathways by which obesity fuels cancer, explains Bernard Fuemmeler, associate director of population science at the VCU Massey Comprehensive Cancer Center and a co-author of the breast cancer study and the colorectal cancer study presented at ASCO. The drugs may also reduce deaths through their effect on cardiovascular disease, he says. Additionally, fat tissue is a source of estrogen, so shrinking fat tissue reduces the hormones that promote certain types of breast cancer tumors.
But some of the new research suggests a mechanism that goes beyond weight loss. GLP-1 drugs could be working on inflammation, which is a key driver linked to tumor development. Chronic inflammation can create conditions that help cancers take root and spread. Because GLP-1 receptors are found throughout the body, not just in the gut and pancreas, activating them appears to dampen inflammation through multiple pathways—such as by acting on immune cells and endothelial cells and other vascular cells or by influencing body-wide inflammatory cascades that affect multiple organs.
GLP-1 drugs might also act on tumors directly. In animal studies, tirzepatide—the dual-receptor drug sold as Zepbound—appears to have target tumors in breast cancer and endometrial cancer, possibly by reversing the inflammatory effects of obesity and inhibiting tumor growth.
Certain cancers might be more responsive to GLP-1 treatment. For instance, the Cleveland Clinic researchers found that, across seven tumor types, people who had tumors packed with GLP-1 receptors were 33 percent less likely to die during the follow up period; people with breast cancer tumors had the greatest improvements in survival. High amounts of such receptors in breast cancer tumors might explain the higher survival rate, but it’s not fully understood, says Mark Orland of the Cleveland Clinic Taussig Cancer Institute, who led the analysis.
“Each of these cancers has to be looked at fairly individually and very specifically, stage by stage and mutation by mutation,” Orland says.
He and his Cleveland Clinic colleague Jaroslaw Maciejewski, a co-author of the research, speculate that the drugs might also be working through something more systemic. Early-stage cancers can only progress in the right environment, one often shaped by aging-related chronic inflammation. “Such an effect would not necessarily be tumor-specific,” Maciejewski says. One possibility is that GLP-1 drugs might be narrowing the gap between chronological age and biological age, the apparent age of various tissues. This could mean GLP-1 drugs may affect biological aging more broadly, the researchers suggest.
Orland says that the field is still far from calling GLP-1 drugs the next big deal for cancer treatment. “It would be a little bit aggressive to say it’s going to cure my cancer or stop my cancer,” he says.
While there isn’t strong evidence to suggest that the drugs worsen cancer in humans, the Food and Drug Administration has warned against their use among people with a family history of certain thyroid cancers, with the agency citing rodent studies. Cancer patients and survivors would also need to carefully monitor their loss of muscle mass, a common side effect of the drugs, during any potential GLP-1-based cancer therapy, Fuemmeler says. For now, clinicians are holding off on prescribing GLP-1 drugs to prevent or treat cancer until there is more research, particularly human clinical trials, which some researchers are already beginning to design. “We don’t know for sure if these [initial] results will hold up in a randomized clinical trial,” Fuemmeler says. “All of these mechanisms are really ripe for future investigation.”