GLP-1 receptor agonists were associated with a 41% lower risk of obesity-related cancers in patients with obesity but without diabetes, according to a new propensity-matched cohort study published in Annals of Oncology.
This is the first large study focused exclusively on non-diabetic patients taking GLP-1s for weight loss. Prior research into GLP-1 drugs and cancer risk has largely included diabetic populations. Researchers at Houston Methodist Hospital designed this study to examine the group now driving most GLP-1 prescriptions: patients with obesity who are not diabetic. The study drew on the TriNetX clinical database, identifying patients with a body mass index of 30 or higher who had clinic visits from December 2014 through June 2025 and were prescribed a GLP-1 drug or diet and exercise. Patients with a diagnostic code associated with diabetes were excluded.
The total study population comprised 229,467 patients, 38% of whom had GLP-1 drug prescriptions and 62% who were prescribed diet and exercise. Propensity matching produced two cohorts of 80,899 patients each.
Here are five things to know.
1. The overall cancer risk reduction was 41% over two years.
After two years of follow-up, the GLP-1 group had a cumulative hazard ratio of 0.59 for eight obesity-associated cancers — a 41% reduction in risk compared with the diet and exercise cohort. The primary outcome measured cumulative incidence of 13 obesity-associated cancers.
2. The risk reduction exceeded 50% for four specific cancers.
Researchers analyzed site-specific incidence for eight of the 13 cancers, finding a consistently lower risk in the GLP-1 cohort. Five of eight reached statistical significance. The largest risk reductions were in multiple myeloma, pancreatic cancer, endometrial cancer and colorectal cancer. Thyroid cancer also reached statistically significant reductions.
3. Tirzepatide showed a dramatically larger risk reduction than semaglutide.
The two most commonly prescribed GLP-1 agonists in the study were semaglutide, sold as Ozempic and Wegovy, and tirzepatide, sold as Mounjaro and Zepbound. Both were associated with significantly lower cancer risk, but tirzepatide showed a reduction of 69% compared with 20% for semaglutide.
“It’s hard to know why that was, but it was a pretty big difference,” said Aparna Kamat, MD, director of the Division of Gynecologic Oncology at Houston Methodist and the study’s senior author. “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.”
4. Men had a larger risk reduction than women — 68% vs. 35%.
Though men made up a smaller share of the study cohorts, they saw substantially greater cancer risk reduction than women. Both sexes achieved statistically significant results.
5. Researchers say cancer prevention should enter the GLP-1 clinical conversation — even before causation is established.
The study adds to a rapidly expanding body of evidence. A separate analysis of 13 obesity-associated cancers published in the past year found a 17% overall reduction in relative risk. At the recent American Society of Clinical Oncology meeting, more than two dozen presentations examined GLP-1 drugs and cancer outcomes, and investigators announced the launch of a prospective breast cancer prevention trial using GLP-1 agonists.
“Based on all of the studies that we have now, we can’t really say there’s a cause-and-effect relationship,” Dr. Kamat 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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