Meta-analysis of GLP-1 receptor agonist trials finds thyroid and colorectal cancer signals
The pooled trial analysis found no overall change in cancer risk with GLP-1 drugs, while thyroid and colorectal cancers showed higher odds and uterine cancer showed lower odds.
A meta-analysis of 50 randomized controlled trials found no overall difference in cancer risk among people taking GLP-1 receptor agonists, but reported higher odds of thyroid cancer and colorectal cancer in separate analyses. The paper was published May 29, 2025, in the journal Diabetes, Obesity and Metabolism [1].
The analysis combined trials that compared GLP-1 receptor agonists with any comparator for diabetes or obesity and lasted at least 52 weeks [1]. Findings were reported for the drug class as a whole. For all cancers combined, the odds ratio was 1.05, with a 95% confidence interval of 0.98 to 1.13 [1]. Because that range includes 1.0, the result was not statistically significant: the data did not show a clear overall increase or decrease in cancer.
Two specific cancers stood out. For thyroid cancer, the odds ratio was 1.55, with a 95% confidence interval of 1.05 to 2.27 [1]. That signal was more evident in longer-term trials [1]. For colorectal cancer, the odds ratio was 1.27, with a 95% confidence interval of 1.03 to 1.57, and that finding was significant only in shorter-term trials [1]. An odds ratio is not the same as an individual's risk: a figure of 1.55 means the odds of the outcome were about 55% higher in the group taking the drug compared with the comparison group.
One cancer went the other way. In trials of people with obesity, uterine cancer was significantly less common in the GLP-1 arm, with an odds ratio of 0.24 and a 95% confidence interval of 0.06 to 0.94 [1]. In trials aimed at diabetes treatment, that reduction was not seen (odds ratio 0.92, 95% confidence interval 0.58 to 1.47) [1]. For every other cancer analyzed, there was no significant difference [1].
The authors gave different readings of the two signals. They wrote that the thyroid finding prompts "the need for further specific studies" [1]. For colorectal cancer, they suggested the small increase in shorter-term trials "may be the effect of a disproportionate increase in diagnostic procedures in the GLP-1 RA arm, because of the suspicion raised by common side effects of GLP-1 RA" [1]. That means more colon exams in the treated group could find more cancers even if the drug is not causing them.
The findings sit alongside other evidence pointing in different directions. The authors note that an observational study recently suggested GLP-1 receptor agonists reduce obesity-associated cancers, while another investigation found no effect on cancer incidence [1]. Their overall conclusion was that the drugs "do not appear to produce an effect on most malignancies in clinical trials," with a possible reduction in some obesity-linked cancers and a thyroid risk signal that needs more work [1].
Why it matters for patients
These are group-level results from trials, not proof that the drugs cause or prevent cancer in any one person. An odds ratio is a statistical estimate, and the authors describe the thyroid finding as a signal rather than an established risk [1].
For thyroid cancer, regulators already take a cautious position with this drug class. The US Food and Drug Administration and the European Medicines Agency state that GLP-1 receptor agonists should be used with caution in patients with a personal or family history of medullary thyroid cancer [1]. Whether the thyroid cancers counted in this analysis were of that type has not been reported, and no link to a specific drug, dose or patient group has been established.
For colorectal cancer, the authors' own explanation points away from a direct drug effect and toward more testing among people taking the drugs. Whether that explanation holds has not been confirmed.
The uterine cancer result was the one clear reduction in the analysis, and it appeared only in trials of people with obesity — the group most likely to benefit from weight loss, which is itself linked to lower cancer risk [1].
What happens next
The paper calls for further specific studies on thyroid cancer but does not announce one, and no timeline for such research has been reported [1]. No change in regulatory guidance is described in the paper [1].
Sources
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