HMN 2025: How GLP-1 receptor agonists likely have little or no effect on obesity-related cancer risk

A systematic review and meta-analysis evaluated the risk for obesity-related cancer associated with glucagon-like peptide-1 receptor agonists (GLP-1RAs) in patients with type 2 diabetes (T2D) or overweight or obesity.

The review found that GLP-1RAs probably have little or no effect on risk for thyroid, pancreatic, breast, or kidney cancer and may have little or no effect on other obesity-related cancers, although certainty of evidence was low for most outcomes. Longer-term studies are needed to clarify potential risks or benefits.

The findings are published in Annals of Internal Medicine.

Researchers from Harvard Medical School and colleagues analyzed 48 placebo-controlled randomized controlled trials (RCTs) involving 94,245 participants that evaluated the efficacy or safety of GLP-1RAs/dual agonists in adult patients with T2DM or overweight or obesity that reported on any of the following cancer outcomes: thyroid, pancreatic, colorectal, gastric, esophageal, liver, gallbladder, breast, ovarian, endometrial, or kidney cancer; multiple myeloma; or meningioma.

RCTs included in the review examined only clinically available and FDA-approved agents such as semaglutide, dulaglutide, and tirzepatide. Most studies had short follow-up and were not designed to assess cancer as a primary outcome. The researchers found that GLP-1RAs probably have little or no effect on risk for thyroid, pancreatic, breast, or kidney cancer.

For other obesity-related cancers such as colorectal, esophageal, and liver cancer, the evidence was of low certainty, and the effect of GLP-1RAs on gastric cancer remains very uncertain. Subgroup and sensitivity analyses showed consistent results across drug classes, doses, and follow-up durations.

The findings offer insights into the safety of GLP-1RAs and suggest no clear signal of increased cancer risk, but longer-term studies with cancer-specific end points are needed to clarify potential risks or protective effects.

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