GLP-1 Receptor Agonist Match Bariatric Surgery in Cancer Prevention: Suggests Study

These findings are published in eClinicalMedicine in May 2025.

While obesity and Type 2 Diabetes Mellitus (T2DM) are established drivers for thirteen specific obesity-related cancers (ORCs), and bariatric metabolic surgery (BMS) has historically demonstrated a 32% to 45% reduction in malignancy incidence in long-term research, a significant clinical gap remains regarding the comparative oncology benefits of modern pharmacotherapy; consequently, Yael Wolff Sagy and colleagues from Clalit Health Services in Israel conducted this investigation to compare the risk of ORC in adults treated with either first-generation receptor agonists or metabolic surgery.

Therefore, the observational, retrospective cohort study utilized electronic medical records from 2010 to 2023 to evaluate 3,178 matched pairs of patients with obesity and T2DM who received either BMS or GLP-1 RAs over a median follow-up of 7.5 years. Researchers analyzed the incidence of thirteen specific malignancies as the primary endpoint, specifically excluding individuals with prior cancer history or end-stage renal disease to ensure a precise assessment of prevention efficacy.

Key Clinical Findings of the Study Include:

• Comparable Incidence: The investigation identified that ORC occurred in 5.64 cases per 1,000 person-years for the medication group versus 5.76 cases for the surgical group, indicating no significant difference between treatments.

• Statistical Parity: Analysis by the study found an adjusted hazard ratio of 1.03, confirming that the choice between medication and surgery does not significantly alter cancer risk over the long term.

• Weight Loss Disparity: Despite the similar oncological protection, surgical patients achieved a markedly higher 31.1% average maximal reduction in BMI compared to a more modest 12.9% reduction in the medication group.

• Independent Protection: Results from the study estimated that the pharmacotherapy provided a 41% relative risk reduction for malignancy that was directly attributed to the drug itself, independent of the effects of weight loss.

• Malignancy Distribution: Out of the 298 total events identified, breast cancer was the most common at 26%, followed by colorectal and uterine cancers.

The results suggest that first-generation GLP-1 RAs are as effective as metabolic surgery in mitigating cancer risk, providing a 41% relative risk reduction that appears to function through pathways beyond simple weight reduction.

These findings suggest to clinicians that the oncology benefits of pharmaceutical obesity management may be driven by metabolic improvements such as reduced systemic inflammation rather than the absolute magnitude of weight loss.

Although the study is constrained by its observational design and the use of older drug generations, it highlights the need for prospective, global randomized controlled trials to further explore the underlying biological mechanisms and validate these effects in broader populations.

Reference

Wolff Sagy Y, Ramot N, Battat E, et al. Glucagon-like peptide-1 receptor agonists compared with bariatric metabolic surgery and the risk of obesity-related cancer: an observational, retrospective cohort study. eClinicalMedicine. 2025;83:103213.