Could GLP-1s Prevent Cancer?

The rapid rise of glucagon-like peptide-1 (GLP-1) agonist drugs for obesity and type 2 diabetes has sparked interest far beyond metabolic health. 

 

Obesity and metabolic dysfunction are associated with increased cancer risk, leading researchers to investigate whether these therapies could also play a role in cancer prevention and treatment. While early findings are encouraging, important questions remain about the biological mechanisms involved and which patient populations may benefit most. 

Dr. Elizabeth Wellberg, an assistant professor of pathology at the University of Oklahoma Health Campus, investigates the relationship between obesity, metabolic disease, and cancer progression. Technology Networks spoke with Wellberg to find out more about why GLP-1 therapies have attracted attention in oncology, the biological pathways that may connect these drugs to cancer outcomes, and the clinical studies that could clarify their future role in cancer care. 

Exploring the link between GLP-1 therapies and cancer risk 

What initially led researchers to suspect that GLP-1 drugs might influence cancer risk or cancer progression? 

Obesity is a well-established risk factor for many types of cancer. “Since GLP-1 therapies are so effective at treating obesity, it seemed logical that they would have anticancer effects as well,” said Wellberg. 

The idea of using GLP-1s for cancer prevention and treatment gained momentum with the publication of numerous retrospective studies that examined past health records to correlate the use of GLP-1s and cancer development. 

For example, a prospective cohort study of more than 1.6 million patients with type 2 diabetes found that patients treated with GLP-1 drugs had a significant risk reduction in 10 obesity-associated cancers, including esophageal, colorectal, kidney, liver, and pancreatic cancers. 

“Now that we have a strong framework showing that GLP-1 therapies reverse obesity and showing that they associate with a lower risk for cancer, we can continue prospective studies that will strengthen the evidence we already have,” explained Wellberg.

 

Prospective studies, where data is gathered as events happen, could be used to identify which cancers and which individuals are most likely to benefit from GLP-1 treatment. 

Evidence for GLP-1s as an anticancer agent: 

• By treating obesity, a significant cancer risk factor, GLP-1s could have anticancer effects. 

• The majority of evidence so far comes from retrospective, observational studies. 

• Prospective studies and further research could pinpoint the cancers and individuals that are most influenced by GLP-1 treatment. 

How obesity and metabolic dysfunction create a pro-cancer environment 

How do obesity, insulin resistance, and other aspects of metabolic disease contribute to cancer development, and where might GLP-1 drugs intervene in those pathways? 

There are several possible mechanisms by which obesity and metabolic disease increase cancer risk. 

People with obesity often have high blood insulin levels and exhibit insulin resistance, which sustains insulin production and delays the removal of glucose from the circulation. Insulin signaling can promote cell proliferation and survival, while excess circulating glucose can fuel rapid cell growth and contribute to cell death resistance, promoting cancer development and progression. 

“By improving insulin sensitivity, GLP-1 therapies help the body quickly respond to insulin and clear glucose, keeping these tumor-promotional factors low over time,” Wellberg explained. 

Obesity is also associated with pro-inflammatory changes in immune cells and dysregulated inflammation, which can drive tumor development. “There is some evidence that GLP-1 drugs can change immune cell profiles in tissues and in tumors in a way that would help the body get rid of cancer cells,” said Wellberg. 

GLP-1 drugs may interfere with obesity-linked, cancer-promoting pathways: 

• GLP-1 drugs can improve insulin sensitivity, reducing levels of circulating insulin and glucose. 

• They may also promote antitumor immune cell phenotypes. 

Separating weight loss effects from direct GLP-1 cancer mechanisms 

How do researchers approach disentangling the potential direct effects of GLP‑1 signaling from the indirect effects of weight loss on cancer risk? 

Observational studies have suggested that weight loss reduces the risk of obesity-related cancers, whether through bariatric surgery or through diet and lifestyle changes. 

This begs the question: are the benefits of GLP-1s for cancer prevention due to their weight loss effects, or other biological mechanisms? 

One prospective study that compared GLP-1s and bariatric surgery for the prevention of obesity-related cancers found that although bariatric surgery caused superior weight loss, cancer risk was 40% lower in people who used GLP-1 drugs, indicating weight-loss-independent anticancer activity. 

However, it is difficult to disentangle the weight loss-mediated effects of GLP-1s from their direct effects. 

“In preclinical models, it is difficult to give GLP-1 therapies without causing weight loss,” Wellberg said. “Some studies have been done in lean models and suggest that these therapies are beneficial, but even then, the individuals do lose weight.” 

By directly testing GLP-1 drugs on cancer cells or immune cells, researchers hope to study their effects that are not mediated by weight loss. However, Wellberg outlined that these studies have had mixed results, largely due to the variable expression of GLP-1 receptors across cell types. 

“It will be important for scientists to use rigorously validated reagents, such as antibodies that recognize the GLP-1 receptor, and to consider the dose of drugs given directly to cancer cells and whether the human body would actually achieve those levels,” Wellberg said. 

“It will also be very interesting to see more studies using these therapies in models or people without obesity, perhaps using lower doses of drugs or even fewer or less frequent doses in a given time frame,” she continued. 

Understanding the direct and indirect mechanisms that mediate GLP-1s' anticancer effects: 

• One of the primary outcomes of GLP-1 treatment is weight loss, which reduces cancer risk. 

• GLP-1s may also have direct effects on cancer and immune cells, but these are difficult to separate from the effects of weight loss. 

• Studying how cancer cells and immune cells respond to GLP-1s in vitro could divorce the direct from the indirect effects. 

Which cancer types could benefit most from GLP-1 therapy? 

Are there specific cancer types where the evidence for a protective effect of GLP-1 therapies is most promising? Could the potential benefits of GLP-1 therapies extend beyond obesity-related cancers? 

Although interest in GLP-1 therapies continues to grow, Wellberg cautioned that definitive evidence for specific cancer types remains limited. 

“Some cancers take longer than others to develop,” Wellberg said. “For example, breast cancer is thought to develop over years or even decades, so it might be a while until we have strong evidence of a preventive effect in this setting.” 

The strongest rationale currently exists for obesity-linked cancers. “I think that we will see the greatest benefit of GLP-1 therapies in those cancers that are strongly promoted by obesity or diabetes, including endometrial cancer, postmenopausal breast cancer, pancreatic cancer, and liver cancer,” said Wellberg. 

However, elucidating the weight-loss-independent anticancer mechanisms of GLP-1s may expand their use to cancers unrelated to obesity. 

“If GLP-1 therapies help the immune system fight cancer, for example, then they would be expected to benefit everyone, not just people with obesity,” Wellberg explained. 

She stressed that this is currently speculation, and further work is needed to determine whether GLP-1s will be beneficial for cancers more broadly. 

Cancer types that may benefit from GLP treatment: 

• Definitive evidence of the anticancer effects of GLP-1s is still emerging, although rationale suggests that obesity-associated cancers will see the greatest benefit. 

• Researchers are exploring whether GLP-1 benefits extend beyond obesity-linked cancers. 

• Additional mechanistic studies are needed to determine whether GLP-1s have broader anticancer activity. 

Defining the role of GLP-1s in oncology 

What kinds of clinical or translational studies are needed to clarify whether GLP-1 drugs help prevent cancer or improve cancer outcomes? How might they fit into cancer prevention and treatment strategies in the future? 

As GLP-1s are unlikely to be prescribed as a sole treatment or preventative, Wellberg is most excited about studies that combine GLP-1 therapies with existing treatments. Clinical trials to assess whether GLP-1s can improve cancer outcomes when used in combination with current approved therapies are ongoing for breast cancer, rectal cancer, and endometrial cancer. 

“These studies will tell us more about the therapeutic effects,” noted Wellberg. 

GLP-1s also need to be trialed to test their effects on cancer prevention. “The prevention studies will need to be done in people at high risk for certain cancers,” said Wellberg. “Although the prevention studies will take longer, they are equally important as the therapeutic trials.” 

In the future, and with further research, GLP-1 drugs may fit into existing cancer prevention and treatment strategies. Their ability to influence weight, metabolism, and potentially immune function makes them attractive candidates for integration into comprehensive care approaches. 

“Their effects in the context of existing cancer treatments will need to be considered, as well as how they impact a patient’s ability to get nutrition and maintain healthy body composition,” noted Wellberg. 

Following clinical trials, researchers and clinicians will need to determine where GLP-1 therapies can provide the greatest benefit while minimizing unintended consequences before they can be introduced in the clinic. 

Future studies and considerations for the use of GLP-1s in oncology: 

• Trials to assess GLP-1s in combination with existing therapeutics are ongoing. 

• The cancer-preventative activity of GLP-1s will also need to be trialed. 

• Including GLP-1s in oncology care will require in-depth consideration. 

This content includes text that has been created with the assistance of generative AI and has undergone editorial review before publishing. Technology Networks' AI policy can be found here.