GLP-1 drugs may be linked to a lower risk of cancer progression, according to new research that will be presented next week at the American Society of Clinical Oncology’s annual meeting.
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The list of health benefits tied to the diabetes and weight loss drugs has been growing — approvals have been expanded to reduce risk of heart disease (Wegovy), to prevent worsening kidney disease (Ozempic) and to treat obstructive sleep apnea (Zepbound) — and researchers continue to look for other possibilities.
The latest research, which is not yet published in a peer-reviewed journal, adds to a growing number of early studies showing that GLP-1s could have anti-cancer effects.
Dr. Mark Orland, an internal medicine physician at Cleveland Clinic, led the study. Orland and his colleagues looked at 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 cancers. All the patients had stage 1, 2 or 3 cancer and started taking a GLP-1 drug after their cancer diagnosis.
It is unclear whether the people in the study were prescribed the medication for diabetes or obesity. As a control, the researchers matched everyone in the GLP-1 group to people with the same type and stage of cancer, and the same comorbidities 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 Type 2 diabetes drug called a DPP-4 inhibitor after their cancer diagnosis.
In every type of cancer except kidney cancer, people who started GLP-1 medications were less likely to have their tumors metastasize, or spread. However, only four of the seven cancers — non-small cell lung cancer, breast cancer, colorectal cancer and liver cancer — had a statistically significant reduction in people whose cancer advanced.
The largest reductions were seen for lung and breast cancer: People with lung cancer who were on GLP-1s were 50% less likely to progress to stage 4 than those taking a DPP-4 inhibitor. For breast cancer, people taking a GLP-1 were 43% less likely to progress. The study was observational, and cannot prove cause and effect. Randomized clinical trials would be needed to prove that GLP-1s could slow cancer progression.
Orland said he suspected the benefits observed were “likely related to the drug itself,” rather than resulting from better controlled diabetes or obesity, which can have an effect on cancer occurrences and outcomes.
Dr. William Troy Donahoo, chief of the division of endocrinology, diabetes and metabolism at the University of Florida in Gainesville who wasn’t involved in the research, also hypothesized the GLP-1 itself explained the benefits. He worked on a study last year that found that taking a GLP-1 was linked to reduced 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 on a tumor may make it more or less responsive to GLP-1 drugs, said Dr. Kelvin Lee, director of Indiana University’s Melvin and Bren Simon Comprehensive Cancer Center, who was not involved in the research.
“If you target a receptor on the tumor cells, it could interfere with communication and not allow it to be as good at spreading,” Lee said.
It’s also possible that targeting GLP-1 receptors could interfere with a process called glycolysis, in which cells convert glucose into energy. Messing with glycolysis in tumor cells effectively cuts off a tumor’s energy supply, Lee said.
Whatever the exact mechanism may be, it’s likely the drugs pack a one-two punch, working both on the tumor cells themselves, as well as their environment, he added. “Cancers are part of a complex ecosystem, the body.”
GLP-1 drugs may tweak the immune system in a way that boosts its cancer-fighting aspects, such as T-cells, and dampens inflammation, which helps tumors thrive.
Further studies will need to establish whether GLP-1 drugs truly do have anti-cancer effects, and dig further into why they may impede some cancers from spreading.
“Each type of cancer has its own puzzle,” Donahoo said.
Lee said that even if the benefits are established, GLP-1 drugs are not likely to be a first-line treatment for any cancer.
Orland said the most important takeaway is that the drugs appear to be safe to use for diabetes or weight loss in people undergoing cancer treatment, though it’s still too soon to recommend GLP-1s for any type of cancer therapy.