Use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) was associated with a 41% lower risk of developing obesity-associated cancers in the short term for obese, nondiabetic patients, according to findings from an observational study published in Annals of Oncology.
“Our study found that over an average follow-up of 2 years, GLP-1 RA use was associated with a significantly lower incidence of cancers directly fueled by excess body weight. Overall cancer risk was reduced by 41% and we saw even larger reductions in certain subgroups, including men, where the risk dropped by nearly 70%. Among gynecologic cancers, there was a 58% reduction in the incidence of endometrial cancer, one of the malignancies most closely linked to obesity," said senior study author Aparna A. Kamat, MD, Director of the Division of Gynecologic Oncology, Houston Methodist Hospital, Houston, Texas.
Background and Study Methods
Researchers conducted a target trial emulation to assess the use of GLP-1 RAs and a possible association with risk of 13 obesity-related cancers. The research team used the nationwide TriNetX database to identify a cohort of 229,467 obese, nondiabetic adults without a prior obesity-related cancer diagnosis between December 2014 and June 2025.
Propensity matching enabled the matching of patients who were prescribed GLP-1 RAs with those receiving diet or exercise counseling. Propensity matching was validated using the inverse probability of treatment weighting.
“We already had evidence suggesting these drugs might reduce cancer risk in diabetic patients, but most of the people now taking GLP-1 RAs for weight loss do not have diabetes. They are younger, obese patients and represent a completely different population. We wanted to investigate whether these medications would affect the risk of obesity-associated cancers in this specific population of patients who make up the majority of GLP-1 RA users in the country—no one had studied this before," Dr. Kamat said.
The primary outcome measure was the cumulative incidence of obesity-related cancers by treatment groups, and the secondary outcome measure was cancer incidence by subgroups, including sex, body mass index, race, and GLP-1 drug.
Key Findings
Of the total identified patients, 37.7% received GLP-1 RAs and 62.3% received diet or exercise consultation. This group was narrowed to a study cohort of 161,798 propensity matched patients.
Patients were followed for a median of 2 years. There was a significantly lower incidence of obesity-related cancers among patients who received GLP-1 RAs (hazard ratio [HR] = 0.59; 95% confidence interval [CI] = 0.53–0.67).
Additionally, GLP-1 RA use was associated with a lower cumulative incidence of obesity-related cancers across all subgroups except for Black race. “The reduction in obesity-related cancer risk among White patients was about 50%, but this risk reduction was not observed among Black patients. This may reflect additional causes such as access to care, differing risk profiles and other biological differences," Dr. Kamat said. “We also studied the different GLP-1 RA formulations and found that while all of them reduced the incidence of obesity-related cancers, the greatest reduction was seen among tirzepatide users.”
Among men, the risk of developing an obesity-related cancer dropped by almost 70%. Additionally, a 58% reduction in the incidence of endometrial cancer was noted. “Given the significant reduction in endometrial cancer incidence among GLP-1 RA users in the study, we are now looking into mechanisms by which GLP-1 RAs may affect endometrial cancer growth and prognosis. We are studying mechanistic pathways that are modulated by these drugs—work that could open new treatment strategies for one of the most common gynecologic malignancies," Dr. Kamat said.
Findings were confirmed by an analysis of the inverse probability of treatment weighting.
“Our study suggests GLP-1 RAs may have benefits that extend beyond weight management," said second study author Pedro T. Ramirez, MD, FACOG, Chair of the Department of Obstetrics and Gynecology at Houston Methodist Hospital. "It should be noted that while the findings do not prove that GLP-1 drugs directly prevent cancer, they provide early evidence that deserves further study in long-term clinical trials."
“For policymakers and other researchers, our study is a clear signal that GLP-1 RAs deserve serious investigation as cancer prevention agents, particularly as obesity-related cancers increasingly affect adults in their 40s and 50s,” Dr. Kamat added.
“This study highlights the potential for a major shift in how we think about obesity treatment and cancer prevention. As the use of GLP-1 RA medications continues to grow worldwide, understanding their broader health impact is critically important,” Dr. Ramirez concluded.
DISCLOSURES: For full disclosures of the study authors, visit annalsofoncology.org.
