GLP-1 Receptor Agonists and Cancer Risk in Adults With Obesity.
Level 3 - non-randomized controlled study
Retrospective propensity score-matched cohort study using electronic health records (target trial emulation).
PubMed 40839273 · doi:10.1001/jamaoncol.2025.2681
What was done
This retrospective cohort study used a target trial emulation design analyzing electronic health record data from 2014 to 2024 across the OneFlorida+ network. Adults aged 18 years or older with obesity who were eligible for antiobesity medications and had no prior cancer history were included. Participants prescribed GLP-1 receptor agonists (GLP-1RAs) were matched 1:1 using propensity scores to eligible nonusers. The primary outcome was the incidence of 14 cancer types (13 obesity-associated cancers plus lung cancer).
What was found
The study analyzed 86,632 matched adults (mean age 52.4 years; 68.2% female), with 43,317 GLP-1RA users and 43,315 nonusers. Total cancer incidence rates were 13.6 vs 16.4 per 1,000 person-years in GLP-1RA users vs nonusers, representing a significantly lower overall cancer risk (hazard ratio [HR] 0.83; 95% CI, 0.76-0.91; P = .002). Lower risks were observed for endometrial cancer (HR 0.75; 95% CI, 0.57-0.99; P = .05), ovarian cancer (HR 0.53; 95% CI, 0.29-0.96; P = .04), and meningioma (HR 0.69; 95% CI, 0.48-0.97; P = .05). GLP-1RA use was associated with an elevated risk estimate for kidney cancer (HR 1.38; 95% CI, 0.99-1.93; P = .04).
Why it matters
These findings suggest that GLP-1RA use in obesity is associated with an overall reduction in cancer incidence, while identifying a potential kidney cancer signal that warrants dedicated long-term surveillance.
Limits
As an observational electronic health record study, residual confounding from unmeasured lifestyle factors, medication adherence, or magnitude of weight loss cannot be ruled out. Multiple site-specific cancer associations had wide confidence intervals with borderline statistical significance, and precise follow-up duration or drug dosages were not reported in the abstract.
Cited by
- supports Studies show that GLP-1 receptor agonists are protective to some degree against obesity-related cancers.