Differential Effects of GLP-1 Receptor Agonists on Cancer Risk in Obesity: A Nationwide Analysis of 1.1 Million Patients


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Differential Effects of GLP-1 Receptor Agonists on Cancer Risk in Obesity: A Nationwide Analysis of 1.1 Million Patients

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated significant efficacy in obesity treatment beyond their original development for type-2 diabetes management. This comprehensive study investigated the relationship between GLP-1RA use and cancer incidence in individuals with obesity across a 5-year follow-up period.

Methods: We conducted a large-scale cohort study using the TriNetX US Collaborative Network database (2013–2023) examining adult patients with obesity. The study utilized propensity score matching to pair GLP-1RA-treated patients with controls (1:1) using the nearest neighbor method. Cancer incidence served as the primary outcome measure over the 5-year follow-up, with subgroup analyses considering individual GLP-1RA agents, patient sex, and BMI categories.

Results: Analysis revealed significant cancer-risk reductions associated with GLP-1RA use across multiple cancer types compared to matched controls. Notable risk reductions were observed in gastrointestinal (HR 0.67, 95% CI 0.59–0.75), skin (HR 0.62, 95% CI 0.55–0.70), breast (HR 0.72, 95% CI 0.64–0.82), female genital (HR 0.61, 95% CI 0.53–0.71), prostate (HR 0.68, 95% CI 0.58–0.80), and lymphoid/hematopoietic cancers (HR 0.69, 95% CI 0.60–0.80). Semaglutide demonstrated superior protective effects, particularly in gastrointestinal cancers (HR 0.45, 95% CI 0.37–0.53). Conversely, liraglutide showed increased risks for thyroid (HR 1.70, 95% CI 1.03–2.82) and respiratory cancers (HR 1.62, 95% CI 1.13–2.32). Conclusions: This research provides compelling evidence for GLP-1RA's potential role in cancer-risk reduction, with semaglutide showing particularly promising results. The differential effects observed among GLP-1RA agents emphasize the importance of personalized medicine approaches. These findings suggest significant implications for clinical practice and future research in both obesity management and cancer prevention. © 2024 by the authors.

Authors : Levy S.; Attia A.; Elshazli R.M.; Abdelmaksoud A.; Tatum D.; Aiash H.; Toraih E.A.

Source : Multidisciplinary Digital Publishing Institute (MDPI)

Article Information

Year 2025
Type Article
DOI 10.3390/cancers17010078
ISSN 20726694
Volume 17

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