The different colorectal tumor risk related to GLP-1 receptor agonists and SGLT2 inhibitors use: a network meta-analysis of 68 randomized controlled trials
Abstract
Background: Recent evidence has raised concerns about potential pro-oncogenic effects associated with glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors, particularly regarding gastrointestinal malignancies. Colorectal tumors, the third most diagnosed cancer globally, already show increased incidence in patients with metabolic disorders who typically require these medications. For example, obese subjects had a significantly higher risk of colorectal tumors than healthy subjects. However, existing evidence on this association remains inconsistent. This network meta-analysis (NMA) evaluated the comparative incidence of colorectal tumors associated with specific GLP-1 receptor agonists and SGLT2 inhibitors.
Materials and methods: We conducted a confirmatory NMA focused specifically on colorectal tumor incidence as an adverse effect, following Cochrane methodological recommendations. We performed a frequentist-based NMA of randomized controlled trials (RCTs) evaluating GLP-1 receptor agonists or SGLT2 inhibitors. Our primary outcome was colorectal tumor incidence, with safety profiles assessed by dropout rates as a secondary outcome.
Results: This NMA encompassing 68 RCTs with 207 200 participants found that only semaglutide was associated with increased incidence of colorectal tumors compared to controls. A dose-stratified analysis revealed that high-dose injectable semaglutide (2.4 mg/week) was the only regimen associated…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 207 participants or records.
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