TOPLINE:
Glucagon-like peptide-1 (GLP-1) receptor agonists used therapeutically for diabetes and weight loss do not elevate gastrointestinal (GI) cancer risk, according to a new meta-analysis by Italian investigators of 90 randomised clinical trials (RCTs) with nearly 125,000 participants.
METHODOLOGY:
- This study was a meta-analysis of 90 RCTs with at least 24 weeks of safety follow-up.
- Studies were identified by a search of Medline/PubMed, Embase, and Scopus databases.
- The risk for bias was evaluated using the revised Cochrane risk-of-bias tool, and certainty of evidence was evaluated with the Grading of Recommendations Assessment, Development, and Evaluation.
- The primary outcome was GI cancer.
TAKEAWAY:
- Participants (mean age was 59.7 years and 43.4% women) were studied for an average of 3.1 years.
- GLP-1 agonists were not associated with any GI cancer (pooled risk ratio [RR], 0.99; 95% CI, 0.86-1.13) relative to placebo or active comparator.
- GLP-1 agonists were not associated with any site-specific GI cancers, such as cancers of the gall bladder, liver, oesophagus, pancreas, and small intestine.
- No increase in GI cancer risk was found by mechanism of action (pure GLP-1 agonists [such as, albiglutide and semaglutide] and dual GLP-1 agonists [tirzepatide and cotadutide]), by route of administration (oral and subcutaneous), and by indication (type 2 diabetes and overweight/obesity).
IN PRACTICE:
The authors concluded that "This meta-analysis found no significant impact of GLP-1 [receptor agonists] on gastrointestinal cancer risk. Long-term safety monitoring of these agents remains important."
They also concluded that the findings were "reassuring" despite "preclinical studies suggesting a potential link between GLP-1 receptor activation and tumorigenesis…"
SOURCE:
The corresponding author is Stefanos Bonovas of Humanitas University and IRCCS Humanitas Research Hospital, Milan, Italy. The study appeared in Pharmacological Research.
LIMITATIONS:
Limitations included potential for insufficient time period to study causation (3.1 years), publication bias, and small-study effects.
DISCLOSURES:
Several authors reported conflicts of interest. The study was partially funded by the Italian Ministry of Health.
