Annals of Oncology: GLP-1 use tied to 41 percent lower obesity-related cancer risk

Adults with obesity and no diabetes who were prescribed GLP-1 receptor agonists had a 41% lower rate of obesity-associated cancers over about two years than similar adults who got diet or exercise counseling, according to a study published in Annals of Oncology ^[2][4]. The researchers, led by a team at Houston Methodist Hospital, say it is the first analysis to isolate this question in people taking the drugs purely for weight loss rather than diabetes ^[3][4].

What the study did

The team used TriNetX, a nationwide database covering 113 million US patients, to find adults with a body mass index of 30 or higher, no diabetes diagnosis, and no prior obesity-related cancer, with clinic visits from December 2014 through June 2025 ^[3][4]. Of 229,467 patients identified, 86,422 (37.7%) were prescribed a GLP-1 drug and 143,045 (62.3%) were prescribed diet and/or exercise ^[3]. After 1:1 propensity score matching, the analysis included 161,798 people: 80,899 in each group ^[3]. Mean age was 47.2 years, about 74% were women, and 76% were white ^[3][4].

The design is called a target trial emulation, which applies trial-like eligibility rules to real-world records, and the findings were checked with a second statistical method, inverse probability of treatment weighting ^[3].

The numbers

With a median follow-up of two years (interquartile range one to two years), GLP-1 users had a hazard ratio of 0.59 (95% confidence interval 0.53–0.67) for developing any of 13 obesity-associated cancers ^[3]. That is the 41% figure in the headlines ^[2][4].

Subgroups varied widely. Men had a risk reduction of about 68% to 70%, compared with 35% in women ^[2][4]. Endometrial cancer, one of the malignancies most tightly tied to body weight, dropped 58% ^[2]. White patients saw roughly a 50% reduction, while no reduction was seen among Black patients ^[2][3]. Senior author Aparna A. Kamat, MD, said that gap "may reflect additional causes such as access to care, differing risk profiles and other biological differences" ^[2].

By drug, the picture splits. MedPage Today reports that tirzepatide (Mounjaro, Zepbound) was linked to a 69% reduction while semaglutide (Ozempic, Wegovy) was linked to a 20% reduction, a hazard ratio of about 0.80 ^[4]. Kamat said it is "hard to know why that was, but it was a pretty big difference," and speculated about tirzepatide's dual GIP and GLP-1 activity and possible anti-inflammatory effects ^[4].

Site-specific results were reported for eight of the 13 cancers, with five reaching statistical significance ^[4]. Event counts were small in absolute terms: multiple myeloma 17 versus 46 cases (HR 0.37), pancreatic 14 versus 35 (HR 0.40), endometrial 35 versus 83 (HR 0.42), colorectal 45 versus 91 (HR 0.49), thyroid 48 versus 77 (HR 0.62), kidney 46 versus 64 (HR 0.72, not significant), ovarian 17 versus 23 (HR 0.74, not significant), and breast 208 versus 251 (HR 0.83) ^[4].

Why it matters for patients

This is an observational study, not a randomized trial, and the authors are explicit that it cannot establish cause and effect. Co-author Pedro T. Ramirez, MD, said the findings "do not prove that GLP-1 drugs directly prevent cancer" but "provide early evidence that deserves further study in long-term clinical trials" ^[2]. The published conclusion says prospective trials are needed to confirm causality ^[3].

People prescribed a GLP-1 drug may differ from people told to diet and exercise in ways that records cannot fully capture, such as engagement with care or screening frequency. Two years is also short for cancer outcomes, and the raw number of cancers in each arm was in the dozens for most sites ^[4]. The apparent gap between tirzepatide and semaglutide comes from a subgroup comparison, not a head-to-head trial, so it is not yet known whether the two drugs truly differ on cancer risk ^[4].

An earlier analysis of the same 13 obesity-associated cancers found a more modest 17% relative reduction, so estimates across studies are not consistent ^[4]. The authors reported no funding and no conflicts of interest ^[3].

What happens next

The paper appears in the August 2026 issue of Annals of Oncology ^[3]. At the recent ASCO meeting, investigators announced the launch of a prospective breast cancer prevention trial using GLP-1 agonists ^[4]. Kamat's group says it is also studying how these drugs may affect endometrial cancer growth at a biological level ^[2].