GLP-1 Receptor Agonists Unlikely to Meaningfully Influence Obesity-Related Cancer Risk, Review Suggests

Key Takeaways:

• Evidence from randomised trials suggests GLP-1 receptor agonists are unlikely to meaningfully increase or reduce the risk of most obesity-related cancers.
  
• For several cancer types, including colorectal, liver and endometrial cancer, the certainty of evidence remains low due to limited follow-up.
  
• Researchers emphasise the need for longer-term studies with cancer-specific outcomes to fully understand potential risks or protective effects.
  

A comprehensive systematic review published online on 8 December in Annals of Internal Medicine suggests that glucagon-like peptide-1 receptor agonists, commonly known as GLP-1 RAs, have little or no effect on the risk of developing cancers associated with obesity.

The review was led by Albert Ko, MD, of the Harvard T.H. Chan School of Public Health in Boston, and examined data from randomised, placebo-controlled trials involving people treated with GLP-1 RAs for type 2 diabetes or overweight and obesity. While these medications have transformed metabolic care in recent years, concerns have persisted about their long-term safety, including potential cancer risk.

Scope and purpose of the review

GLP-1 receptor agonists are widely prescribed for glycaemic control and weight management, yet their association with cancer has remained uncertain. To address this gap, the researchers conducted a systematic review and meta-analysis to assess whether treatment with GLP-1 RAs is associated with an increased or reduced risk of obesity-related cancers.

The review focused on cancers known to have strong links with excess adiposity, including thyroid, pancreatic, colorectal, gastric, oesophageal, liver, gallbladder, breast, ovarian, endometrial and kidney cancers. It also included multiple myeloma and meningioma.

Data sources and study selection

The authors searched PubMed, Embase, Web of Science, Scopus and the Cochrane Central Register of Controlled Trials from database inception through to August 2025. Only randomised, placebo-controlled trials reporting at least one of the specified cancer outcomes were eligible for inclusion.

In total, 48 trials met the inclusion criteria, encompassing 94,245 participants. None of the trials had been specifically designed to evaluate cancer outcomes, and follow-up durations were generally short.

Methods and quality assessment

Risk of bias across the included trials was assessed using the Cochrane Risk of Bias 2 tool. The certainty of evidence for each outcome was evaluated using the GRADE framework, which considers factors such as study limitations, consistency of results and precision of estimates.

Pooled odds ratios were calculated using random-effects meta-analysis to account for variation between studies.

Main findings by cancer type

The analysis found that GLP-1 receptor agonists probably have little or no effect on the risk of several common obesity-related cancers, based on evidence of moderate certainty.

Specifically:

• Thyroid cancer showed no clear association with GLP-1 RA use, with an odds ratio of 1.37 (95% CI, 0.82 to 2.31), corresponding to between one fewer and nine more cases per 10,000 people treated.
  
• Pancreatic cancer risk was similarly unaffected, with an odds ratio of 0.84 (95% CI, 0.53 to 1.35), equating to nine fewer to six more cases per 10,000 people.
  
• Breast cancer showed an odds ratio of 0.95 (95% CI, 0.60 to 1.49), indicating no meaningful difference in risk.
  
• Kidney cancer also demonstrated no significant association, with an odds ratio of 1.12 (95% CI, 0.78 to 1.60).
  

For other cancers, including colorectal, oesophageal, liver, gallbladder, ovarian and endometrial cancer, as well as multiple myeloma and meningioma, the evidence suggested little or no effect. However, the certainty of this evidence was rated as low.

For gastric cancer, the findings were described as very uncertain, reflecting sparse data and wide confidence intervals.

Consistency across analyses

The results remained consistent across multiple sensitivity and subgroup analyses. These included analyses restricted to trials with a low risk of bias, studies involving newer agents such as semaglutide or tirzepatide, and comparisons across different follow-up durations, populations, GLP-1 RA classes, doses, weight-loss profiles and durations of action.

This consistency strengthens confidence that the observed lack of association is not driven by a specific drug, dose or patient group.

Limitations of the evidence

The authors highlight important limitations that temper the conclusions. Most notably, the included trials were not designed to detect cancer outcomes and generally had relatively short follow-up periods. As a result, rare cancers or effects that emerge only after prolonged exposure may not have been captured.

Implications and next steps

Summarising the findings, the authors conclude that GLP-1 receptor agonists “may have little or no effect on risk for obesity-related cancers,” while emphasising the need for further research. As they write, “These findings offer important insights into the safety of GLP-1 RAs but highlight the need for longer-term studies with cancer-specific end points to clarify potential risks or protective effects.”

For clinicians and people considering or already using GLP-1 receptor agonists, the review provides a degree of reassurance regarding cancer risk in the short to medium term. However, ongoing surveillance and dedicated long-term studies will be essential as use of these medications continues to expand globally.