Risk of neoplasms with semaglutide in patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials

Background Semaglutide is prescribed in conjunction with diet and exercise to improve glycemic control in adults with type 2 diabetes (T2DM). However, its potential impact on tumorigenesis has prompted considerable debate. Methods The meta-analysis was conducted in accordance with PRISMA 2020 guidelines. We searched Web of Science, PubMed, Embase, and ScienceDirect for eligible randomized controlled trials (RCTs). The outcome was the risk of overall, benign and malignant neoplasms. The pooled results were expressed as odds ratio (OR) with 95% confidence interval (95% CI). Influential publication was determined by performing the sensitivity analysis. Publication bias was assessed using the funnel plot, Begg’s and Egger’s tests. Results Nineteen RCTs conducted between 2016 and 2025 were included, enrolling of 38,160 patients with T2DM. The interventions involved subcutaneous semaglutide and oral semaglutide, with treatment durations ranging from 26 to 156 weeks. Fixed-effects meta-analysis revealed that semaglutide use was associated with an increased risk of overall neoplasms (OR = 1.19, 95% CI = 1.07 to 1.32, P = 0.001) and benign neoplasms (OR = 1.28, 95% CI = 1.02 to 1.61, P = 0.032), but showed no significant association with malignant neoplasms (OR = 1.12, 95% CI = 1.00 to 1.26, P = 0.054). No influential publications or significant publication bias were detected. Conclusion Semaglutide use in patients with T2DM is associated with a modestly increased risk of overall and benign neoplasms, but not malignant neoplasms. These findings highlight the importance of maintaining clinical awareness regarding potential neoplastic risks, and further long-term RCTs are warranted to clarify their clinical significance. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420261354386 , Identifier CRD420261354386.