GLP1-RAs help fight cancers in adults with overweight, obesity

New research indicates that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may confer a protective effect against cancers in adults with overweight or obesity regardless of type 2 diabetes (T2D) status.

In a retrospective cohort of 43,317 GLP-1RA users and 43,315 propensity-score matched nonusers, the incidence rate of cancers was 13.6 vs 16.4 per 1,000 person-years, respectively. The overall cancer risk was 17-percent lower among GLP1-RA users (hazard ratio [HR], 95 percent confidence interval [CI], 0.76–0.91; p=0.002). [JAMA Oncol 2025;doi:10.1001/jamaoncol.2025.2681]

The 14 cancer types included 13 that were related to obesity—such as liver, thyroid, pancreatic, bladder, colorectal, kidney, breast, endometrial, meningioma, upper gastrointestinal, ovarian, multiple myeloma, and prostate—and lung cancer.

GLP-1RA use was specifically associated with a reduced risk of endometrial cancer (HR, 0.75, 95 percent CI, 0.57–0.99; p=0.05), ovarian cancer (HR, 0.53, 95 percent CI, 0.29–0.96; p=0.04), and meningioma (HR, 0.69, 95 percent CI, 0.48–0.97; p=0.05).

Interestingly, GLP-1RAs were also associated with a marginal increase in the risk of kidney cancer (HR, 1.38, 95 percent CI, 0.99–1.93; p=0.04).

“This study is one of the first to assess the association between GLP-1RA use and cancer risk in the broad, real-world population with obesity or overweight who are eligible for weight-loss medications,” the investigators said.

The findings are consistent with those of prior research in T2D patients showing similar reductions in the risk of endometrial, ovarian, and meningioma cancers. “These patterns raise the hypothesis that GLP-1RAs may be associated with a lower risk of hormone-sensitive malignant neoplasms,” the investigators said. [Commun Biol 2022;5:614; Cancers (Basel) 2023;15:980]

They emphasized that even modest changes in cancer risk could have substantial public health implications, considering that more than 137 million individuals in the US alone are currently eligible for GLP-1RA therapies.

Meanwhile, the biological mechanisms linking GLP-1RAs and kidney cancer remain unclear, especially given that the drugs have been shown to improve kidney function in other studies, the investigators noted. “Further research is needed to clarify this potential risk.” [JAMA Netw Open 2024;7:e2440286; Lancet Diabetes Endocrinol 2025;13:15-28]

For the study, the investigators applied a target trial emulation design using electronic health record data from a multicentre health research network that integrates real-world clinical data from diverse healthcare settings in the US.

A total of 86,632 matched adults (mean age 52.4 years, 68.2 percent female, 44.2 percent non-Hispanic White) were included in the analysis. Of these, 50.7 percent had T2D, and 48.3 percent had obesity (BMI ≥30 kg/m²).

Additional analyses that used interpretable decision tree to find specific patient groups who might respond differently to GLP-1RA therapy showed that depression appeared to modify treatment response. For endometrial cancer, patients with depression who took GLP-1RAs saw a modest reduction in their cancer risk, whereas those without depression who were also taking oral corticosteroids did not get the same benefit. For meningioma, the protective effect of GLP-1RAs was seen only in patients who were also taking antidepressants. Finally, for kidney cancer, depression was again associated with a potential protective signal, whereas substance use was linked to increased risk, suggesting a possible harmful interaction.

“These findings highlight the importance of tailored risk assessments and underscore the need for further long-term studies to clarify the impact of GLP-1RAs on cancer risk in high-risk populations,” the investigators said.