Warning: semaglutide promotes growth of GLP-1 receptor-expressing neuroendocrine tumors by 72% in mice | Research

The takeaway

Semaglutide promoted tumor growth by 19-22% in vitro and 72% in vivo in neuroendocrine neoplasm cells expressing GLP-1 receptors, raising safety concerns for NET patients prescribed GLP-1 drugs.

72% tumor growth increase
Semaglutide accelerated GLP-1R-positive neuroendocrine tumor growth by 72% in mice—a critical safety signal for NET patients

What the researchers found

3 of 6 NET cell lines expressed high GLP-1R. Semaglutide increased GOT1 growth 19%, NT-3 growth 22% in vitro. In vivo: semaglutide increased GOT1 xenograft tumor volume by 72%. GLP-1R expression correlated with growth response.

Why it matters

As millions take semaglutide for weight loss and diabetes, patients with undiagnosed or known neuroendocrine tumors could be at risk of accelerated tumor growth. This is the first systematic study demonstrating this concern with in vivo evidence.

How the study worked

GLP-1R quantification by qPCR, immunofluorescence, and Western blot in 6 NET cell lines. Semaglutide treatment with cell viability assays. In vivo GOT1 xenograft model with semaglutide treatment and tumor volume measurement.

What this study cannot tell us

Preclinical study. Only one xenograft model. Dose used in mice may not reflect human clinical doses. NET heterogeneity means some tumors may not respond. No human patient data.

How to read the evidence

Preclinical study with both in vitro mechanism and in vivo xenograft validation. Strong for a safety signal but needs human epidemiological confirmation.

When this study was published

Published in 2025; raises urgent safety questions as GLP-1 drug use expands.

The bigger picture

This study raises a critical pharmacovigilance concern. NETs are often slow-growing and may be undiagnosed when patients start GLP-1 drugs. Clinicians should consider NET screening in patients with relevant symptoms before or during GLP-1 therapy.

Questions still open

Should patients be screened for NETs before starting GLP-1 therapy?
Do epidemiological data show increased NET incidence in GLP-1 drug users?
At what GLP-1R expression threshold does tumor growth promotion occur?

Common questions

Can semaglutide cause cancer?

This study shows semaglutide can accelerate growth of neuroendocrine tumors that express GLP-1 receptors—but this does not mean it causes cancer in general. The concern is specifically for patients who already have or are developing neuroendocrine tumors, which may grow faster with GLP-1 drug stimulation.

Should I stop taking semaglutide?

Do not stop medication without consulting your doctor. This finding applies specifically to neuroendocrine tumors, which are rare. If you have symptoms like flushing, diarrhea, or unexplained abdominal pain while on GLP-1 drugs, discuss with your healthcare provider. The overwhelming majority of patients benefit from GLP-1 therapy.

Read the original research

GLP-1R agonist promotes proliferation of neuroendocrine neoplasm cells expressing GLP-1 receptors.

Surgery, 179, 108943

View on PubMed ↗Publisher’s paper ↗

Citation

Shilyansky, Jonathan S; Chan, Casandro J; Xiao, Sophia; Gribovskaja-Rupp, Irena; Quelle, Dawn E; Howe, James R; Dillon, Joseph S; Ear, Po Hien. (2025). GLP-1R agonist promotes proliferation of neuroendocrine neoplasm cells expressing GLP-1 receptors.. Surgery, 179, 108943. https://doi.org/10.1016/j.surg.2024.09.052