A meta-analysis of six randomized controlled trials including 13,391 participants found no increased risk of esophageal cancer with GLP-1 receptor agonist use, with a pooled relative risk of 0.46 — suggesting these drugs may even have a protective trend.
RR 0.46 — no increased cancer riskPooling data from 13,391 participants across 6 RCTs, GLP-1 receptor agonists showed a non-significant trend toward reduced esophageal cancer risk with zero heterogeneity between studies.
What the researchers found
The pooled relative risk of esophageal cancer in patients using GLP-1 receptor agonists compared to control agents was 0.46 (95% CI 0.13-1.59; p=0.725; I²=0%), indicating no increased risk and a non-significant trend toward reduced risk. There was no heterogeneity between studies (I²=0%).
Subgroup analyses stratified by age, intervention duration, BMI category, and indication (T2DM vs. obesity) consistently showed no association between GLP-1 RA use and increased esophageal cancer risk. No significant within-class differences were found among different GLP-1 receptor agonists.
Why it matters
As GLP-1 receptor agonists become some of the most prescribed drugs worldwide, questions about long-term cancer safety are critical. Esophageal cancer was a specific concern because GLP-1 drugs can cause gastrointestinal side effects including acid reflux, which is a risk factor for esophageal cancer. This meta-analysis provides reassuring evidence from the highest quality study type — randomized controlled trials — that these drugs do not increase esophageal cancer risk.
How the study worked
Systematic literature search and meta-analysis of six randomized controlled trials comparing GLP-1 receptor agonists to control agents in adults with type 2 diabetes or obesity (total n=13,391). Bias risk and study quality were assessed. Statistical analysis used Stata 18.0 and R 4.0.2. Subgroup analyses were performed by age, treatment duration, BMI, and indication. The study was pre-registered (PROSPERO CRD42024543945).
What this study cannot tell us
Only six studies met inclusion criteria, and the total number of esophageal cancer events was likely very small, limiting statistical power. The relatively short duration of most RCTs may not capture cancers that develop over many years. All data came from RCTs, which may not fully represent real-world patient populations. The non-significant p-value (0.725) means the apparent protective trend cannot be confirmed.
How to read the evidence
This is a meta-analysis of randomized controlled trials — the highest tier in the evidence hierarchy. The pre-registered protocol and use of RCTs rather than observational studies strengthens the evidence. However, the small number of cancer events limits the statistical power of the conclusions.
When this study was published
Published in 2025, this meta-analysis captures the most current available RCT data on GLP-1 agonist cancer safety. As more long-term trial data accumulate, future analyses will provide greater certainty.
The bigger picture
This meta-analysis is part of a broader effort to evaluate the long-term safety of GLP-1 receptor agonists as their use expands to tens of millions of patients globally. Cancer safety is one of the most important questions for any widely prescribed long-term medication, and this analysis adds to growing evidence that GLP-1 drugs do not increase cancer risk — and may even have protective effects against certain cancers through weight loss and anti-inflammatory mechanisms.
Questions still open
- Would longer follow-up periods reveal a more definitive protective effect of GLP-1 agonists against esophageal cancer?
- Does the GLP-1 drug-related weight loss account for the trending reduction in esophageal cancer risk, given that obesity is a major risk factor?
- Are there differences in esophageal cancer risk among specific GLP-1 receptor agonists (semaglutide vs. liraglutide vs. others)?
Common questions
Do GLP-1 drugs like Ozempic cause esophageal cancer?
Why were researchers concerned about esophageal cancer with these drugs?
Read the original research
A meta-analysis on the risk of esophageal cancer in type 2 diabetes patients treated with GLP-1 receptor agonists.
Frontiers in endocrinology, 16, 1532587
Citation
Wu, Qi; Zeng, Yan; Liu, Yong; Teng, Fangyuan; Zhou, Tiejun; Guo, Man; Jiang, Zongzhe; Xu, Yong. (2025). A meta-analysis on the risk of esophageal cancer in type 2 diabetes patients treated with GLP-1 receptor agonists.. Frontiers in endocrinology, 16, 1532587. https://doi.org/10.3389/fendo.2025.1532587