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

A systematic review and meta-analysis that 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, has found that the drugs 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. However, the researchers from Harvard Medical School stated the certainty of evidence was low for most outcomes and longer-term studies are needed to clarify potential risks or benefits.

In total, the review analysed 48 placebo-controlled randomised 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, oesophageal, liver, gallbladder, breast, ovarian, endometrial, kidney cancer multiple myeloma and meningioma.

The 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.

GLP-1RAs probably have little or no effect on risk for thyroid cancer (OR, 1.37 [95% CI, 0.82 to 2.31]; 1 fewer to 9 more cases per 10 000 patients treated), pancreatic cancer (OR, 0.84 [CI, 0.53 to 1.35]; 9 fewer to 6 more per 10 000), breast cancer (OR, 0.95 [CI, 0.60 to 1.49]; 10 fewer to 12 more per 10 000), or kidney cancer (OR, 1.12 [CI, 0.78 to 1.60]; 5 fewer to 13 more per 10 000) (moderate certainty).

In addition, GLP-1RAs may have little or no effect on colorectal, oesophageal, liver, gallbladder, ovarian, or endometrial cancer; multiple myeloma; or meningioma (low certainty). The effect on gastric cancer is very uncertain. 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-1RA class, weight loss profile, dose and duration of action.

The outcomes 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.

The findings were featured in the paper, 'Risk for Cancer With Glucagon-Like Peptide-1 Receptor Agonists and Dual Agonists: A Systematic Review and Meta-analysis', published in the Annals of Internal Medicine. To access this paper, please click here (log-in maybe required)