Large Study Links GLP-1s to Lower Risk of Multiple Cancers

Patients taking GLP-1 receptor agonists for obesity had a 41% lower risk of obesity-related cancers as compared with patients treated with diet or exercise, a large propensity-matched cohort study showed.

After 2 years of follow-up, the GLP-1 group had a cumulative hazard ratio of 0.59 for eight obesity-associated cancers. Analyses of the different cancers showed a consistently lower risk for GLP-1 users, achieving statistical significance for five of the eight cancers evaluated. The risk reduction exceeded 50% for multiple myeloma, pancreatic cancer, endometrial cancer, and colorectal cancer. Men and women alike had significant risk reductions with GLP-1 drugs.

The results add to a rapidly expanding volume of evidence linking use of GLP-1 agonists to a lower risk of cancer but is the first specifically limited to patients taking the drugs for weight loss, reported Aparna Kamat, MD, of Houston Methodist Hospital, and colleagues in Annals of Oncology.

“If you think about the people who are actually taking [GLP-1 drugs], the majority of them are taking GLP-1 receptor agonists for weight loss,” Kamat told MedPage Today. “These are patients who are obese and not diabetic. They are essentially being prescribed GLP-1 agonists for weight loss. Our study is the first to actually look at this population.”

The two most commonly prescribed GLP-1 agonists in the study, semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound), were associated with significantly lower cancer risk, but the reduction was substantially greater in patients on tirzepatide compared with semaglutide (69% vs 20%), she added.

“It’s hard to know why that was, but it was a pretty big difference,” said Kamat. “Tirzepatide and some of the other newer agents have dual activity [targeting GIP and GLP-1], and they also work on some glucocorticoid receptors, so maybe there’s an added action against inflammation.”

In just the past year, multiple studies have linked GLP-1 drug use to lower cancer risk and better cancer-related outcomes, including an analysis of 13 obesity-associated cancers, which showed a more modest overall reduction in relative risk (17%). At the recent American Society of Clinical Oncology (ASCO) meeting, more than two dozen presentations focused on the relationship between GLP-1 drug use and cancer, including a study showing a reduced risk of metastasis for four types of cancer among patients taking GLP-1 agonists versus other types of antidiabetic medications.

For their study, Kamat and colleagues searched the TriNetX clinical database to identify patients with obesity (body mass index ≥30) who had clinic visits from December 2014 through June 2025 and were prescribed a GLP-1 drug or diet and/or exercise. Patients with a diagnostic code associated with diabetes were excluded, as were patients prescribed a GLP-1 drug plus diet and/or exercise. Inclusion also was limited to patients with 2 years of follow-up. The primary outcome was cumulative incidence of 13 obesity-associated cancers.

The total study population comprised 229,467 patients, 38% of whom had GLP-1 drug prescriptions and 62% who were prescribed diet and/or exercise. Propensity matching produced two cohorts of 80,899 patients each. The two cohorts had a median age of 47, 74% were women, and 76% were white.

The primary analysis showed a 41% reduction in the hazard for any obesity-associated cancer in patients treated with a GLP-1 agonist. Men, who accounted for a smaller proportion of the cohorts, had a substantially larger risk reduction (68% vs 35% for women). The investigators analyzed site-specific incidence for eight of the 13 cancers, showing a consistently lower risk in the GLP-1 drug cohort:

• Multiple myeloma: 17 vs 46 (HR 0.37, 95% CI 0.21-0.64)
• Pancreatic cancer: 14 vs 35 (HR 0.40, 95% CI 0.22-0.74)
• Endometrial cancer: 35 vs 83 (HR 0.42, 95% CI 0.28-0.63)
• Colorectal cancer: 45 vs 91 (HR 0.49, 95% CI 0.35-0.71)
• Thyroid cancer: 48 vs 77 (HR 0.62, 95% CI 0.43-0.89)
• Kidney cancer: 46 vs 64 (HR 0.72, 95% CI 0.49-1.05)
• Ovarian cancer: 17 vs 23 (HR 0.74, 95% CI 0.39-1.38)
• Breast cancer: 208 vs 251 (HR 0.83, 95% CI 0.69-0.996)

During the ASCO meeting, investigators announced the launch of a prospective breast cancer prevention trial with GLP-1 agonists. Would Kamat consider enrolling patients in such a trial?

“Based on all of the studies that we have now, we can’t really say there’s a cause-and-effect relationship,” she said. “But in patients who, for example, need to lose weight or who are diabetic and are candidates for GLP-1s, I definitely feel that the discussion should also include potential cancer prevention. As long as the indications of the inclusion criteria are reasonable, I think that we are probably going to see more and more people looking at this, because the associations are pretty striking.”

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