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A retrospective analysis of 359,595 adults with type 2 diabetes found lower estimated obesity-related cancer risk among GLP-1 receptor agonist users than among insulin or sulfonylurea users. The association was most consistent in people with lower-severity diabetes; researchers found no significant overall difference versus metformin, DPP-4 inhibitors or SGLT2 inhibitors. The study cannot show that any medication prevents or causes cancer.
A retrospective study of 359,595 adults with type 2 diabetes found that users of GLP-1 receptor agonists had lower estimated risk of obesity-related cancers than patients treated with insulin or sulfonylureas, with the clearest differences among those whose diabetes was less severe at treatment start. The analysis, published in JAMA Network Open, found no significant overall cancer-risk differences compared with metformin, DPP-4 inhibitors or SGLT2 inhibitors, and does not establish that GLP-1 drugs prevent cancer.
At three years, the estimated risk of obesity-related cancer was 2.01% for GLP-1 receptor agonist users, compared with 3.26% for insulin users. In a separate comparison, the estimate was 2.85% for GLP-1 users and 3.98% for people taking sulfonylureas. These are results from different active-comparator analyses, not a direct comparison among all five medication groups.
For the insulin comparison, the association favored GLP-1 treatment across diabetes-severity categories at three years, but reached statistical significance in the overall analysis and among patients with low-severity diabetes. The study reported a similar pattern at five years. Against sulfonylureas, statistically significant differences at three years appeared in the overall and low-severity analyses; the overall and low-severity findings remained significant at five years.
Results were less consistent for other comparators. Cancer risk did not differ significantly between GLP-1 drugs and metformin, DPP-4 inhibitors or SGLT2 inhibitors overall. Among people with moderate- or high-severity diabetes, SGLT2 inhibitor treatment was associated with lower risk than GLP-1 treatment during the first three years. The authors said the comparisons were intended to identify patterns, not prove one treatment superior for cancer outcomes.
Why the Medication Comparison Matters
The findings suggest that cancer-risk associations cannot be interpreted without asking which treatments are being compared and what patients’ health was like before they began them. Insulin and sulfonylureas may be used at different stages of diabetes or for different clinical reasons than GLP-1 drugs. Those differences in treatment history and underlying health can complicate attempts to attribute later cancer outcomes to a medication.
For patients and clinicians, the study is not a reason to switch a suitable diabetes treatment solely over cancer concerns. Decisions still need to reflect a person’s glucose control, cardiovascular and kidney health, other medical needs and the established benefits and risks of available therapies. The results are broadly reassuring about GLP-1 use in the comparisons studied, but they do not establish a protective effect.
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How Researchers Compared Treatments
Obesity and diabetes are both associated with increased cancer risk, and earlier observational studies have reported lower rates of some obesity-related cancers among GLP-1 drug users. The new analysis adds a focus on baseline diabetes severity and compares GLP-1 receptor agonists with several other medication classes rather than treating all non-GLP-1 users as one group.
Researchers led by Jesús Gibran Hernández-Pérez of UT Southwestern Medical Center used electronic health record data from PCORnet. They identified adults treated at a single center from January 2010 through July 2025 and conducted five active-comparator analyses. Severity was classified using complications documented before treatment, including macrovascular disease, stages of diabetic kidney disease and other cardiometabolic conditions. Outcomes were examined after three and five years.
Because this was a retrospective cohort study, it analyzed existing medical records rather than assigning patients randomly to treatments. The authors adjusted their comparisons, but such analyses can still be affected by differences between people who receive different medications.
“When we talk about GLP-1 receptor agonists and cancer risk, we need to ask, ‘Compared with which medication, and in which patients?'”
— Jesús Gibran Hernández-Pérez, study author, speaking to MedPage Today
What the Study Cannot Establish
The analysis shows associations, not cause and effect. It cannot determine whether GLP-1 drugs lower cancer risk, whether differences reflect the medications or the health and treatment histories of the people prescribed them, or whether another factor contributed. Adjustment for recorded characteristics does not eliminate all potential confounding in retrospective data.
Some subgroup estimates were not statistically significant. For example, among patients with the most severe diabetes in the sulfonylurea comparison, the estimated association went in the direction of higher cancer risk with GLP-1 treatment, but the difference was not statistically significant. That result should not be read as evidence of increased risk. The available report also does not establish how the findings apply beyond the patients and care setting studied, or to cancer outcomes beyond the obesity-related cancers analyzed.
How Clinicians May Use These Results
The report does not announce a change to treatment guidance or identify a planned follow-up study. For now, clinicians and patients can treat the findings as additional observational evidence, not as a basis for choosing a diabetes drug solely to alter cancer risk. The research team’s stated emphasis is on interpreting results in light of baseline health and treatment history.
Further studies would be needed to test whether the associations persist in other patient populations and settings, and to clarify how diabetes severity and treatment selection relate to cancer outcomes. Until then, the authors advise against changing an otherwise appropriate treatment on the basis of this analysis alone.
Key Questions
Did the study show that GLP-1 drugs prevent cancer?
No. It found lower observed risk than with insulin and sulfonylureas in some comparisons, but a retrospective study cannot establish that GLP-1 drugs prevent cancer.
Which medications were compared with GLP-1 receptor agonists?
The researchers analyzed comparisons with insulin, sulfonylureas, metformin, DPP-4 inhibitors and SGLT2 inhibitors. Results differed across those medication groups.
Why did diabetes severity matter?
The observed differences were clearest in patients with low-severity diabetes. The authors said baseline health and treatment history may shape both which drug a person receives and later outcomes.
Should patients change medication because of these findings?
The study’s lead author said patients should not change an otherwise appropriate treatment solely to reduce cancer risk based on these results. Treatment decisions should be made with a clinician and reflect individual medical needs.
Source: medpagetoday.com
