Despite excitement over a potential link between GLP-1 drugs and reduced cancer risk, new research suggests that popular drugs “likely have little or no effect” on a person’s risk of developing one of 13 obesity-linked cancers.
The findings, published Monday in Annals of Internal Medicine, may seem counterintuitive, said co-author Dr. Cho-Han Chiang, 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 can cause weight loss, and so if obesity increases the risk of cancer, then, hypothetically, losing weight with GLP-1 might actually reduce the risk of developing cancer,” said Chiang, now a medical oncology researcher at Northwell Health Cancer Institute in New York. “That was the excitement in all this research into GLP-1 and cancer risk.”
As a result, previous research had suggested that the drugs – including Ozempic and Zepbound – could help reduce the risk of cancer. For example, a 2024 study published in the journal JAMA Network Open showed that people with type 2 diabetes who took GLP-1 had a significantly reduced risk of 10 obesity-related cancers. However, this study was observational, Chiang said, meaning it analyzed existing patient data rather than conducting a clinical trial. Patients who took GLP-1 may have had access to better health care and a lower risk of cancer, he said.
Chiang and colleagues, on the other hand, reviewed 48 randomized controlled trials involving a total of 94,245 patients with type 2 diabetes and overweight or obesity. Of these, more than 51,000 took a GLP-1 drug, while almost 43,000 took a placebo. Patients were observed for a median follow-up period of 70 weeks.
The researchers focused on the 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 certainty.
The researchers found, with moderate certainty, that GLP-1 drugs had little or no effect on the risk of developing four types of obesity-related cancers: breast, kidney, thyroid, and pancreatic cancers.
The results were similar for eight other obesity-related cancers – liver, gallbladder, colorectal, ovarian, endometrium, esophagus, meningioma (a tumor of the lining of the brain) and multiple myeloma (cancer of the blood cells) – but with low certainty. The effect of GLP-1 on gastric cancer risk was “highly uncertain,” the authors write.
“It’s not that GLP-1 doesn’t reduce cancer risk; I don’t think we can draw that conclusion from our study,” Chiang said. “I would say GLP-1 [drugs] probably does not increase the risk of cancer. It’s a little different.
Longer term studies are needed
The new study has two major limitations, Chiang said. The first is that none of the nearly 50 trials his team analyzed were designed to measure cancer outcomes.
Dr. Kandace McGuire, chief of breast surgery at Virginia Commonwealth University’s Massey Comprehensive Cancer Center, said that could explain the counterintuitive nature of the results.
“When you take a set of studies that didn’t look at cancer risk and you mix them together, sometimes you find things that are contrary to what you would imagine,” said McGuire, who was not involved in the research. “This may be due in part to the composition of the studies, rather than the data themselves.”
“From a cancer prevention perspective, I think more data is needed,” Chiang said, noting that there is also a lack of data on the use of GLP-1 in patients who already have cancer.
Another limitation of the research was its relatively brief follow-up period, less than a year and a half.
Patients prescribed GLP-1 should be monitored much longer, especially for slow-growing diseases like breast and thyroid cancers, McGuire said.
“You really don’t know when in a person’s life they will have a clinically significant cancer,” McGuire said. “Even if you don’t make a difference in the first two or three years, you can make a difference in five or ten years by continuing to use” GLP-1s.
Can GLP-1 increase the risk of certain cancers?
The Food and Drug Administration warns people with a personal or family history of a rare form of thyroid cancer, medullary thyroid carcinoma, from taking certain GLP-1 medications. However, these boxed warnings come from decade-old research on rodents, Chiang said.
“Once there’s an association with a drug, it’s hard to push it away,” he said.
Results from human studies have been mixed, according to Dr. Bassel El-Rayes, deputy director of the O’Neal Comprehensive Cancer Center at the University of Alabama at Birmingham. One study, for example, found an association between GLP-1 and increased risk of thyroid cancer, but only during the first year of drug use.
El-Rayes said he found the results of Chiang’s research promising.
“This study gives us more reassurance about the use of these drugs in treating problems like obesity and type 2 diabetes,” said El-Rayes, who was not involved in the study. “There are questions that remain unanswered, like: Could this protect against cancer? Could there be a slight increase in risk that we don’t recognize yet?”
He added: “Patients using these medications right now are safer than we thought before this article was published. »
Still, El-Rayes cited tobacco-related cancers as an example of the need for longer-term research on GLP-1.
“If you look at people who have smoked for a year, you may not see a big impact of tobacco use,” he said. “We need to follow them longer to really see the effects of tobacco on the development of cancer. »
“Of course,” he added, “we are not saying that GLP-1 [drugs] are as risky as smoking. We are not saying that at all.
Dr. Susan Wolver, a colleague of McGuire’s, directs 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 usually not a priority.
“No one comes to me and says, ‘I’d like to take medication to reduce my risk of cancer,'” said Wolver, who was not involved in the research. “They take these medications to lose weight, to improve their diabetes, their sleep apnea, their heart failure – all their obesity-related conditions, but not cancer.”
Wolver praised the rigor of Chiang’s research, noting that it broke down the analyzes based on factors such as the type of GLP-1, including older versions of the drug approved more than a decade ago.
Because GLP-1 drugs are relatively young — the FDA only approved Wegovy and Zepbound for weight loss in 2021 and 2023 respectively — doctors and scientists have a lot to learn about their long-term effects on the body, Wolver said. Even so, 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 relieved by the results of this study that there doesn’t appear to be an increase in cancer signals,” Wolver said, “but I’m also not dismayed that there wasn’t a reduction in cancer development or metastasis, because I think we just didn’t have enough time.”
