GLP-1s Linked to Lower Risk of Cancer Spread in Four Tumor Types

CHICAGO — Use of GLP-1 receptor agonists in patients with four solid tumor types was significantly associated with lower rates of progression to metastatic disease over a 5-year period, a propensity score-matched analysis found.

In patients with stage I-III colorectal, liver, breast, or lung cancers, those who started a GLP-1 drug after their cancer diagnosis had a 31% to 50% lower risk of progression to stage IV disease compared with patients who initiated another class of antidiabetic drug, DPP-4 inhibitors, reported Mark David Orland, MD, of the Cleveland Clinic Taussig Cancer Institute.

For two of the other three cancers examined — prostate, pancreatic, and kidney — rates of progression to metastatic disease in the GLP-1 drug group were numerically lower, but the differences were not statistically significant, he said at a press briefing ahead of the American Society of Clinical Oncology (ASCO) annual meeting.

Initially approved for type 2 diabetes and obesity, GLP-1 drugs now carry indications in cardiovascular disease, chronic kidney disease, steatotic liver disease, and more, with an estimated 20 million Americans taking the blockbuster medications that include semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound).

In people with diabetes, said Orland, the risk of developing certain tumor types — cancers that rely on high sugar and inflammatory environments — can be up to twice as high.

But GLP-1 agents have never been considered to just be glucose-lowering drugs, with anti-inflammatory and immune modulatory properties hinting at broader effects, along with emerging preclinical data suggesting possible anti-tumor activity.

Time to Prescribe? Not Yet, Experts Say

While calling for prospective studies, Orland and panelists at the briefing said it’s too soon to start prescribing GLP-1 drugs as a means of slowing disease progression.

“This is provocative data that we want to be really exploring very carefully. It doesn’t apply to all patients, all cancers,” said Eric Small, MD, a prostate cancer specialist at the University of California San Francisco Helen Diller Family Comprehensive Cancer Center. “I’m not convinced that the data is there for prostate cancer.”

“Not yet,” said Jennifer Ligibel, MD, of the Dana-Farber Cancer Institute in Boston. “The drugs are really interesting, and there is no doubt that they have changed the landscape of weight loss, but I don’t think we have enough cancer-specific information yet.”

Findings from numerous population-based studies on the connection between GLP-1 receptor agonists and cancer continue to accumulate, but most of the data published have investigated whether the agents may have a cancer prevention effect, noted briefing moderator Julie Gralow, MD, the chief medical officer at ASCO.

“So this study is somewhat unique in that it showed a reduction of metastatic recurrence in those already diagnosed with cancer,” said Gralow. “Is this a direct impact of the GLP-1 agents or are GLP-1 users more health-engaged in general? We’ll need a randomized trial to prove causation.”

The analysis presented by Orland adjusted for confounding variables, but another reason for caution is that the TriNetX database used in the study doesn’t always capture every relevant piece of patient information.

A recent study that used the database found a link between GLP-1 drugs and lower mortality and recurrence risk in breast cancer patients, but outside experts flagged gaps in the dataset that could have influenced results, such as missing tumor characteristics and treatment history.

Study Details

The analysis presented by Orland pulled data from the TriNetX Global Health Research Network and included 10,225 patients who started a GLP-1 drug after a diagnosis of one of seven obesity-related cancers: non-small cell lung cancer (NSCLC); adenocarcinomas of the breast, prostate, pancreas, or colorectum; hepatocellular carcinoma (HCC); and renal cell carcinoma. All patients initially had stage I-III disease.

That group was matched by age, race, body mass index, cancer treatment, and other factors to individuals who started a DPP-4 inhibitor.

The final matched cohort of 12,112 patients were roughly 55-60% white, 20-25% Black, and 10-15% Asian. The most common cancer type was NSCLC (36%), followed by breast cancer (20%), prostate cancer (17%), colorectal cancer (13%), renal cell carcinoma (9%), HCC (5%), and pancreatic cancer (2%).

Over 5 years, rates of progression to metastatic disease were significantly lower in the group using GLP-1 drugs compared with the DPP-4 inhibitor group for four tumor types:

• Colorectal cancer: 13% vs 22% (HR 0.69, 95% CI 0.54-0.88, P=0.003)
• HCC: 19% vs 28% (HR 0.62, 95% CI 0.44-0.89, P=0.009)
• Breast cancer: 10% vs 20% (HR 0.57, 95% CI 0.46-0.71, P<0.001)
• NSCLC: 10% vs 22% (HR 0.50, 95% CI 0.43-0.59, P<0.001)

Orland said that no increased risk was observed for adverse events such as pancreatitis, which can be seen with GLP-1 drugs and in cancer patients.

To help understand why the drugs are associated with benefit, the researchers used the Cancer Genome Atlas to examine whether GLP-1 receptor expression for the seven cancer types was linked with survival. Here they found that high expression was associated with a 33% lower risk of death overall and as much as a 45% lower risk in breast cancer.

Please enable JavaScript to view the comments powered by Disqus.