Drugs with GLP-1 or semaglutide may be linked to a lower risk of cancer progression, according to new research to be presented next week at the annual meeting of the American Society of Clinical Oncology.
The list of health benefits associated with diabetes and weight loss drugs has been growing – approvals have expanded to reduce the risk of heart disease (Wegovy), prevent worsening of kidney disease (Ozempic) and treat obstructive sleep apnea (Zepbound) – and researchers continue to look for other possibilities.
The latest research, which has not yet been published in a peer-reviewed journal, adds to a growing number of preliminary studies showing that GLP-1 could have anti-cancer effects.
Dr. Mark Orland, an internist at the Cleveland Clinic, led the study. Orland and his colleagues analyzed patient records from the TriNetX Global Health Research Network database, identifying more than 10,000 people who had been diagnosed with one of seven types of cancer: breast, colorectal, kidney, liver, lung, pancreatic and prostate. All patients had stage 1, 2, or 3 cancer and began taking a GLP-1 medication after their cancer diagnosis.
It is unclear whether people in the study were prescribed the medication for diabetes or obesity. As a control, the researchers matched everyone in the GLP-1 group with people with the same type and stage of cancer, and the same morbidities, such as obesity or smoking, to make the groups as similar as possible. The difference was that people in the control group started taking a different medication for type 2 diabetes, llbeloved DPP-4 inhibitorafter his cancer diagnosis.
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In all types of cancer except kidney cancer, people who started taking GLP-1 drugs were less likely to have their tumors metastasize or spread. However, only four of the seven cancer types – non-small cell lung cancer, breast cancer, colorectal cancer and liver cancer – showed a statistically significant reduction in people whose cancer progressed.
The largest reductions were seen in lung and breast cancer: People with lung cancer taking GLP-1 were 50% less likely to progress to stage 4 than those taking a DPP-4 inhibitor. In the case of breast cancer, people taking GLP-1 were 43% less likely to progress. The study was observational and cannot demonstrate a cause and effect relationship. Randomized clinical trials would be needed to demonstrate that GLP-1 could slow cancer progression.
Orland said he suspected the benefits seen were “probably related to the drug itself,” rather than the result of better control of diabetes or obesity, which can influence the onset and course of cancer.
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Dr. William Troy Donahoo, chief of the division of endocrinology, diabetes and metabolism at the University of Florida in Gainesville, who was not involved in the research, also hypothesized that GLP-1 itself accounted for the benefits. Last year he worked on a study that found that taking GLP-1 was linked to a lower risk of developing cancer.
The new study offered a clue as to why: Among those taking GLP-1 receptor agonists, those whose tumors had more GLP-1 receptors were less likely to have their cancer metastasize, the researchers said.
Future research should focus on better understanding how the number of GLP-1 receptors in a tumor can make it more or less responsive to GLP-1 drugs, said Dr. Kelvin Lee, director of the Indiana University Melvin and Bren Simon Comprehensive Cancer Center, who was not involved in the research.
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“If a receptor on tumor cells is attacked, it could interfere with communication and prevent it from spreading so easily”Lee stated.
It’s also possible that targeting GLP-1 receptors could interfere with a process called glycolysis, in which cells convert glucose into energy. Disrupting glycolysis in tumor cells effectively cuts off the tumor’s energy supply, Lee explained.
Whatever the exact mechanism, it is likely that the drugs have a dual effect, acting both on the tumor cells themselves and on their environment, he added. “Cancers are part of a complex ecosystem: the body.”
GLP-1 drugs could modify the immune system in such a way that they enhance their cancer-fighting aspects, such as T cells, and reduce inflammation, which favors the growth of tumors.
More studies will be needed to determine whether GLP-1 drugs actually have anti-cancer effects and to further investigate why they might prevent the spread of some types of cancer.
“Each type of cancer has its own puzzle,” Donahoo said.
Lee added that, even if the benefits are confirmed, it is unlikely that GLP-1 drugs become a first-line treatment for any type of cancer.
Orland said the most important conclusion is that the drugs appear to be safe for treating diabetes or weight loss in people receiving cancer treatment, although it is still too early to recommend GLP-1 for any type of cancer therapy.
