GLP-1 receptor agonists are associated with lower kidney cancer risk after metabolic bariatric surgery

Vollständiger Abstract

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Abstract Background Kidney cancer (KC) is an obesity-related malignancy with rising incidence. Although metabolic and bariatric surgery (MBS) reduces the risk of some obesity-related cancers, the use of glucagon-like peptide-1 receptor agonists (GLP-1 RA) has increased after MBS; however, their association with KC risk remains unclear. We aimed to evaluate whether initiation of GLP-1 RA, compared with other glucose-lowering agents, is associated with KC among adults with prior MBS and type 2 diabetes (T2D), and overweight, or obesity. Methods We conducted a retrospective cohort study using TriNetX, applying an active-comparator, new-user target trial emulation framework. Adults (≥18 years) with T2D, obesity/overweight and prior MBS (2006–2025) were included, excluding those with prior cancer or type 1 diabetes. GLP-1 RA initiation was compared with metformin, insulin, sodium–glucose cotransporter 2 inhibitors (SGLT2i), or sulfonylureas. Time zero was the first post-MBS prescription after a 365-day washout. Propensity score matching (1:1) balanced baseline characteristics. The outcome was incident KC (ICD-10 C64, C65). Risk differences (RDs), and hazard ratios were estimated over 5 years. Results After matching, 16 768 GLP-1–metformin, 25 025 GLP-1–insulin, 8 613 GLP-1–SGLT2i, and 7 029 GLP-1–sulfonylurea pairs were included. GLP-1 RA initiation was associated with lower 5-year KC risk vs metformin (RD −0.18%; 95% CI −0.27 to −0.09), insulin (−0.22%; −0.30 to −0.15), SGLT2i (−0.19%; −0.34 to −0.04), and sulfonylureas (−0.20%; −0.37 to −0.03). Results were consistent across sensitivity analyses. Conclusions Among post-MBS patients, GLP-1 RA initiation was associated with lower KC risk vs other therapies, supporting potential oncologic safety and benefits beyond glycemic control.