The development of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) has revolutionized the management of obesity and type 2 diabetes. The agents offer therapeutic potential in a host of other conditions, including cardiovascular, liver, and neurodegenerative diseases, as well as the possibility of reducing the risk of obesity-related cancers. However, a systematic review and meta-analysis evaluating the risk for obesity-related cancers among patients with overweight, obesity, and/or type 2 diabetes using GLP-1 RAs use in patients likely have little or no effect on the risk for obesity-related cancers. Longer-term studies with cancer-specific endpoints are needed to clarify the potential risks or benefits of these medications, according to the study authors. The study by Ko et al is published in Annals of Internal Medicine.
Study Methodology
The researchers analyzed data from PubMed, Embase, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials to identify studies published from inception to August 2025. Their review included 48 placebo-controlled randomized controlled trials reporting outcomes in patients with thyroid, pancreatic, colorectal, gastric, esophageal, liver, gallbladder, breast, ovarian, endometrial, or kidney cancers. The analysis involved 94,245 participants.
Risk of bias was evaluated using the Cochrane Risk of Bias 2 tool, and certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Odds ratios (ORs) were pooled using random-effects meta-analysis.
Results
The researchers found that GLP-1 RAs probably have little or no effect on the risk for thyroid cancer (OR = 1.37, 95% confidence interval [CI] = 0.82–2.31; 1 fewer to 9 more cases per 10,000 patients treated), pancreatic cancer (OR = 0.84, 95% CI = 0.53–1.35; 9 fewer to 6 more per 10,000), breast cancer (OR = 0.95, 95% CI = 0.60–1.49; 10 fewer to 12 more per 10,000), or kidney cancer (OR = 1.12, 95% CI = 0.78–1.60; 5 fewer to 13 more per 10,000), with moderate certainty).
GLP-1 RAs may have little or no effect on colorectal, esophageal, liver, gallbladder, ovarian, or endometrial cancer; multiple myeloma; or meningioma (low certainty), concluded the researchers.
The agents’ effect on gastric cancer is very uncertain, and the researchers noted that the results were consistent in sensitivity analyses of trials with low risk of bias and studies of semaglutide or tirzepatide and across subgroups stratified by follow-up duration, population, GLP-1 RA class, weight loss profile, dose, and duration of action.
“GLP-1 RAs may have little or no effect on risk for obesity-related cancers. Longer-term studies are needed to clarify potential risks or benefits,” concluded the study authors.
Disclosures: For full disclosures of the study authors, visit acpjournals.org.
