Assessing the Oncological Safety of Glucagon-Like Peptide-1 Receptor Agonists: A Systematic Review and Meta-Analysis

Glucagon-like peptide-1 (GLP-1) receptor agonists are essential for treating type 2 diabetes and promoting weight loss. Despite their therapeutic benefits, concerns have arisen regarding their potential association with pancreatic and thyroid cancers. This systematic review and meta-analysis examined the correlation between GLP-1 receptor agonists and cancer incidence in obese/overweight individuals, including both patients with diabetes and overweight/obese non-diabetic participants. A systematic search of PubMed, Scopus, and Cochrane databases identified randomized clinical trials (RCTs) for inclusion. Data extraction and risk of bias assessment followed rigorous methodologies, using the Risk of Bias 2 tool. Of the 1,882 identified studies, nine RCTs (9,078 participants) met the inclusion criteria. The studies varied in duration (12-104 weeks) and demographics, with a mean participant age of 46.9 years and a mean body mass index of 36.9 kg/m². In non-diabetic overweight/obese participants, GLP-1 receptor agonists significantly reduced body weight and HbA1c levels compared to placebo. However, varying incidences of neoplasms were observed, with liraglutide showing a statistically significant odds ratio of 2.8150 for cancer risk. Semaglutide trials have reported mixed results, with some studies showing an increase in neoplasm events in the intervention groups. Although GLP-1 receptor agonists effectively manage weight and glycemic control in overweight/obese patients, their association with increased cancer risk warrants cautious application, especially in individuals with a predisposition to thyroid or pancreatic cancers. Further studies are needed to conclusively determine the safety profile of these therapies.