Risk for Cancer With Glucagon-Like Peptide-1 Receptor Agonists and Dual Agonists : A Systematic Review and...

Area of Science:

• Endocrinology and Metabolism
• Oncology
• Pharmacology

Background:

• Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely prescribed for type 2 diabetes mellitus (T2DM) and obesity.
• The potential association between GLP-1RA use and cancer risk remains an area of significant clinical interest and uncertainty.

Purpose of the Study:

• To systematically evaluate the risk of various obesity-related cancers in patients treated with GLP-1RAs.
• To synthesize evidence from randomized controlled trials to inform clinical practice and patient counseling.

Main Methods:

• A comprehensive meta-analysis was conducted on data from 48 randomized placebo-controlled trials, including over 94,000 participants.
• Searches were performed across major databases (PubMed, Embase, Web of Science, Scopus, Cochrane) up to August 2025.
• Risk of bias and certainty of evidence were assessed using the Cochrane Risk of Bias 2 tool and GRADE approach, respectively.

Main Results:

• GLP-1RAs demonstrated little to no effect on the risk of thyroid, pancreatic, breast, or kidney cancers (moderate certainty evidence).
• Evidence of low certainty suggests no significant impact on colorectal, esophageal, liver, gallbladder, ovarian, or endometrial cancers, multiple myeloma, or meningioma.
• The effect on gastric cancer risk remains uncertain due to limited data.

Conclusions:

• Current evidence suggests that GLP-1RAs are unlikely to increase the risk of most obesity-related cancers.
• The findings are robust across sensitivity analyses, including studies on specific agents like semaglutide and tirzepatide.
• Longer-term clinical trials are necessary to definitively ascertain the long-term cancer risks and benefits associated with GLP-1RA therapy.