ABSTRACT

IMPORTANCE Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely prescribed for glycemic control in type 2 diabetes and have recently gained popularity for weight management. However, their long-term impact on cancer risk remains uncertain. Understanding this association is crucial for patient safety.
OBJECTIVE To compare the incidence of 14 cancers among adults with obesity prescribed GLP-1RAs vs nonusers.
DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study followed a target trial
emulation design using 2014 to 2024 electronic health record data from OneFlorida+, a multicenter health research network that integrates real-world clinical data from diverse health care settings. Adults 18 years or older eligible for antiobesity medications without prior cancer history were included. Participants were categorized as GLP-1RA users or nonusers, matched 1:1 using propensity scores.
EXPOSURE Individuals taking vs not taking GLP-1RAs.
MAIN OUTCOMES AND MEASURES The primary outcomes were the incidence of 14 cancer types, including 13 obesity-associated cancers (liver, thyroid, pancreatic, bladder, colorectal, kidney, breast, endometrial, meningioma, upper gastrointestinal, ovarian, multiple myeloma, and prostate) and lung cancer.
RESULTS A total of 86 632 matched adults (mean [SD] age, 52.4 [14.5] years; 68.2% female) were included, comprising 43 317 GLP-1RA users and 43 315 otherwise eligible nonusers. The incidence rates of the 14 cancers were 13.6 vs 16.4 per 1000 person-years, respectively, indicating a significantly lower overall cancer risk among individuals taking GLP-1RAs (hazard ratio [HR], 0.83 [95% CI, 0.76-0.91]; P = .002) compared with nonusers. In particular, taking GLP-1RAs was associated with a reduced risk of 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). However, GLP-1RAs were associated with a marginally nonsignificant increased risk of kidney cancer (HR, 1.38 [95% CI, 0.99-1.93]; P = .04).
CONCLUSIONS AND RELEVANCE This retrospective cohort study found that taking GLP-1RAs
was associated with a reduced overall risk of cancer, including lower risks of endometrial, ovarian, and meningioma cancers, among patients with obesity or overweight. However, taking GLP-1RAs may be associated with an increased risk of kidney cancer, highlighting the need for longer-term follow-up to clarify the underlying mechanisms and clinical implications of these findings.