GLP-1 drugs like Ozempic or Zepbound may not affect risk of 13 obesity-related cancers

Despite previous excitement around a potential connection between GLP-1 drugs and reducing cancer risk, new research shows that popular drugs “likely have little or no effect” on a person's risk of developing one of 13 obesity-related cancers.

The results, published Monday in the journal Annals of Internal Medicine“This may seem counterintuitive,” said co-author Dr. Cho-Han Chan, who conducted the study earlier this year as an internal medicine resident at Mount Auburn Hospital, a teaching hospital of Harvard Medical School in Cambridge, Massachusetts.

“GLP-1 may cause people lose weight“And so if obesity increases the risk of cancer, then, hypothetically, losing weight with GLP-1 might actually reduce the risk of cancer,” said Chan, now an oncology fellow at Northwell Health Cancer Institute in New York. “That was the excitement in the whole study of GLP-1 and cancer risk.”

Accordingly, previous studies have shown that these drugs, including Ozempic and Zepbound, may help reduce cancer risk. For example, a 2024 study published in the journal The JAMA Network is open showed that people with type 2 diabetes who took GLP-1 significantly reduced their risk of 10 obesity-related cancers. However, according to Chang, the study was observational in nature, meaning it analyzed existing patient data rather than conducting a clinical trial. Patients taking GLP-1 may have initially had access to better medical care and a lower risk of cancer, he said.

Chan and colleagues, on the other hand, analyzed 48 randomized controlled trials involving 94,245 patients with type 2 diabetes who were overweight or obese. Of these, more than 51,000 took the GLP-1 drug and nearly 43,000 took a placebo. Patients were followed for a median follow-up period of 70 weeks.

The researchers focused on 13 types of obesity-related cancers identified by the International Agency for Research on Cancer Working Group and their possible links to GLP-1 drugs, with varying levels of statistical significance.

The researchers found with moderate confidence that GLP-1 drugs had little effect on the risk of developing four types of cancer associated with obesity: breast, kidney, thyroid and pancreatic.

The results were similar for eight other obesity-related cancers—liver, gallbladder, colorectalovarian, endometrial, esophageal, meningioma (tumor of the lining of the brain) and multiple myeloma (blood cell cancer) – but with low confidence. The effect of GLP-1 on gastric cancer risk was “very uncertain,” the authors wrote.

“It's not that GLP-1 doesn't reduce cancer risk; I don’t think we can draw that conclusion based on our study,” Chan said. “I would say GLP-1 [drugs] probably do not increase the risk of cancer. It's a little different.”

Long-term studies needed

The new study has two main limitations, Chang said. First, none of the nearly 50 studies his team analyzed were designed to evaluate cancer outcomes.

Dr. Candace McGuire, chief of breast surgery at Virginia Commonwealth University's Massey Comprehensive Cancer Center, said this may explain the inconsistent nature of the findings.

“When you take multiple studies that haven't looked at cancer risk and put them together, sometimes you find things that contradict your assumptions,” said McGuire, who was not involved in the study. “Some of this may simply be a result of the research rather than the actual data itself.”

“I think more data is needed from a cancer prevention perspective,” Chan said, noting that there is also not enough data on the use of GLP-1 among patients who already have cancer.

Another limitation of the study was the relatively short follow-up period of less than one and a half years.

Patients prescribed GLP-1 should be followed much longer, especially for slow-growing diseases such as breast and thyroid cancer, McGuire said.

“You really don’t know when someone will develop clinically significant cancer in their life,” McGuire said. “While you may not make a difference in the first two to three years, you can make a difference in five to 10 years with continued use” of GLP-1.

Can GLP-1s increase the risk of developing certain types of cancer?

The Food and Drug Administration warns people with a personal or family history of a rare form of thyroid cancer, medullary thyroid cancer, against taking certain GLP-1 drugs. However, such warnings are based on decades of rodent research, Chan said.

“Once you have an association with a drug, it’s hard to get rid of it,” he said.

According to Dr. Bassel El-Reyes, associate director of the O'Neill Comprehensive Cancer Center at the University of Alabama at Birmingham, results from human studies have been mixed. One studyfor example, found an association between GLP-1 and an increased risk of thyroid cancer, but only during the first year of taking the medication.

El-Reyes said he finds the results of Chang's study promising.

“This study gives us more confidence in using these drugs to treat diseases such as obesity and type 2 diabetes,” said El-Reyes, who was not involved in the study. “There are questions that remain unanswered, such as: Could this protect against cancer? Could there be a slight increase in risk that we don't yet recognize?”

He added: “Patients who are currently taking medications are safer than we thought before this article came out.”

However, El-Reyes cited tobacco-related cancers as an example of the need for long-term studies of GLP-1.

“If you look at people who smoked for one year, you might not see much of an impact from tobacco use,” he said. “You need to follow them over a longer period of time to really see the impact of tobacco on cancer development.”

“Of course,” he added, “we are not saying that GLP-1 [drugs] just as dangerous as using tobacco. We don’t say that at all.”

Dr. Susan Woolver, a colleague of McGuire's, runs the medical weight loss program at VCU Health. She said that when she counsels patients about the benefits and risks of GLP-1 drugs, cancer is not usually the focus.

“Nobody comes to me and says, 'I wish I could take some medicine to reduce my risk of cancer,'” said Woolver, who was not involved in the study. “They take these medications to lose weight, improve diabetes, sleep apnea, heart failure—all conditions associated with obesity, but not cancer.”

Wolver praised the thoroughness of Chang's study, noting that the analyzes were broken down by factors such as GLP-1 type, including older versions of the drug that were approved more than a decade ago.

Because GLP-1 drugs are relatively new (the FDA hasn't approved Wegovy and Zepbound for weight loss until 2021 and 2023, respectively), doctors and scientists still have a lot to learn about their long-term effects on the body, Woolver said. Despite this, the observed benefits of GLP-1, such as improving blood pressure and reducing the risk of heart failure, outweigh the known risks, she said.

“I'm pleased with the findings from this study that there don't seem to be any increased cancer signals,” Woolver said, “but I'm also not alarmed that there was no reduction in cancer development or metastasis, because I think we just didn't have enough time.”