Weight Loss, Obesity Medication, and Risk of Obesity‐Associated Cancer: A Meta‐Analysis of Randomized Controlled Trials

ABSTRACT Objective This study aimed to determine whether weight reduction mediated by antiobesity medications (AOMs) contributes to the risk reduction in obesity‐associated cancer. Methods PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and the ClinicalTrials.gov website were systematically searched for randomized controlled trials of AOMs from inception to December 2024. Relative risks were calculated using a random‐effects model. Results The analysis included 25 randomized controlled trials with 40,731 participants. Compared with placebo, AOMs showed no association with the risk of overall obesity‐related cancer (RR = 1.03, 95% CI: 0.78 to 1.37) or site‐specific cancer. Consistently, every 5 kg weight reduction mediated by AOMs was not associated with the risk of overall obesity‐related cancer (RR = 0.97, 95% CI: 0.84 to 1.12) or site‐specific cancer. However, subgroup analysis revealed that coagonists (tirzepatide, cotadutide, and cagrilintide) significantly reduced overall obesity‐associated cancer risk (RR = 0.43, 95% CI: 0.19 to 0.97), and every 5 kg weight reduction mediated by coagonists was marginally associated with a reduced overall obesity‐associated cancer risk (RR = 0.79, 95% CI: 0.62 to 1.00). Conclusions Weight reduction mediated by current AOMs was not associated with a reduced risk of overall or site‐specific obesity‐associated cancer in patients with overweight or obesity, while a decreased risk of overall obesity‐associated cancer was observed in coagonist users.