GLP-1 drugs linked to 41% lower obesity-related cancer risk in large study

Adults with obesity and no diabetes who were prescribed GLP-1 receptor agonists had a 41% lower incidence of obesity-associated cancers over a median of two years than similar adults who received diet or exercise counseling, according to a study published in Annals of Oncology ^[2][3][4].

The researchers used TriNetX, a nationwide database of 113 million US patients, to identify 229,467 obese, nondiabetic adults with no prior diagnosis of an obesity-associated cancer, seen between December 2014 and June 2025 ^[2][3]. Of those, 86,422 (37.7%) were prescribed a GLP-1 drug and 143,045 (62.3%) received diet or exercise counseling ^[2][3]. After 1:1 propensity score matching, the study compared 80,899 GLP-1 users with 80,899 people who got counseling alone ^[2][3]. Mean age was 47.2 years (standard deviation 14.8) ^[3]; in the matched groups the median age was 47, about 74% were women and 76% were white ^[4].

The primary result was a hazard ratio of 0.59 (95% confidence interval 0.53–0.67) for any obesity-associated cancer among GLP-1 users, a 41% reduction ^[2][3]. An inverse probability of treatment weighting analysis confirmed the finding ^[2][3].

Subgroup results varied widely. Men had a reduction of nearly 70%, compared with 35% for women ^[2][4]. Endometrial cancer incidence fell 58%, with a hazard ratio of 0.42 (95% CI 0.28–0.63) ^[2][4]. By drug, the reduction was substantially larger for tirzepatide (Mounjaro, Zepbound) at 69% than for semaglutide (Ozempic, Wegovy, Rybelsus) at 20%, senior author Aparna Kamat, MD, of Houston Methodist Hospital, told MedPage Today ^[4]. "It's hard to know why that was, but it was a pretty big difference," Kamat said, noting that tirzepatide targets both GIP and GLP-1 ^[4]. The ASCO Post reported that all the GLP-1 formulations studied reduced obesity-associated cancer incidence, with the greatest reduction among tirzepatide users ^[2].

For individual cancers, the study reported site-specific results for 8 of the 13 obesity-associated cancers it tracked, and the difference reached statistical significance for five ^[3][4]. Risk reductions exceeded 50% for multiple myeloma (hazard ratio 0.37, 95% CI 0.21–0.64), pancreatic cancer (0.40, 0.22–0.74), endometrial cancer (0.42, 0.28–0.63) and colorectal cancer (0.49, 0.35–0.71) ^[4]. Thyroid cancer also showed a significant reduction (0.62, 0.43–0.89) ^[4]. Kidney cancer (0.72, 0.49–1.05), ovarian cancer (0.74, 0.39–1.38) and breast cancer (0.83, 0.69–0.996) had smaller differences, with confidence intervals that crossed or nearly crossed 1.0 for kidney and ovarian cancer ^[4].

One subgroup did not show the benefit. GLP-1 use was associated with a lower cumulative incidence of obesity-associated cancers in all subgroups except Black race, according to the study and the ASCO Post ^[2][3]. "The reduction in obesity-related cancer risk among White patients was about 50%, but this risk reduction was not observed among Black patients," Kamat said, adding that this may reflect access to care, differing risk profiles and other biological differences ^[2]. The study was funded by none declared, and the authors reported no conflicts of interest ^[3].

Why it matters for patients

The study is observational. It compares people who happened to get a prescription with people who did not, so it cannot show that the drugs caused the lower cancer rates. "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," said second author Pedro T. Ramirez, MD, of Houston Methodist Hospital ^[2].

Median follow-up was only two years, and the study tracked short-term incidence, not cancer deaths or survival ^[2][3]. Whether the pattern holds over longer periods has not been reported. A separate earlier analysis of 13 obesity-associated cancers found a more modest 17% reduction in relative risk ^[4], and the researchers said prospective trials with longer follow-up are needed to determine whether the associations reflect a causal effect ^[3].

Use of GLP-1 drugs among obese, nondiabetic adults in the US rose from about 21,000 patients in 2019 to more than 174,000 in 2023, according to the study ^[3] — the population most of these new findings apply to ^[2].

What happens next

The authors say prospective, randomized studies with longer follow-up are needed to test whether GLP-1 drugs actually reduce cancer incidence ^[2][3]. Kamat said her group is now studying mechanisms by which GLP-1 receptor agonists may affect endometrial cancer growth and prognosis ^[2]. At the recent American Society of Clinical Oncology meeting, researchers announced the launch of a prospective breast cancer prevention trial with GLP-1 agonists; no start date was disclosed ^[4].