Cancer
Comparative Effects of GLP-1 Receptor Agonists and Other Glucose-Lowering Drugs on Kidney Cancer Risk: A Target Trial Emulation in Post-Bariatric Patients Jesus Hernandez* Jesus Hernandez Hernandez Hernandez Hernandez Hernandez Hernandez Hernandez Hernandez Hernandez Hernandez Hernandez Peter O’Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, Texas
Importance: Kidney cancer (KC) is an obesity-related malignancy with rising incidence. Metabolic and bariatric surgery (MBS) has been shown to reduce the risk of some obesity-related cancers, yet the effect of post-surgical glucose-lowering therapies on the incidence of KC remains poorly understood. Use of glucagon-like peptide-1 receptor agonists (GLP-1 RA) is rising after MBS for weight and glycemic control; however, little is known about its effect on the incidence of KC among patients who underwent MBS.
Objective: To assess whether initiation of GLP-1 RA compared with other glucose-lowering agents is associated with KC risk in post-MBS patients with overweight, obesity, or type 2 diabetes (T2D).
Design, Setting, and Participants: This retrospective cohort study followed a target trial emulation design that included adults (≥18 years) with prior MBS between January 1, 2006, and January 1, 2025. Individuals with prior cancer, type 1 diabetes, or severe comorbidities were excluded.
Exposures: Initiation of GLP-1 RA (semaglutide, dulaglutide, liraglutide, exenatide, lixisenatide, albiglutide, or tirzepatide) was compared separately with metformin, insulin, sodium–glucose cotransporter 2 inhibitors (SGLT2i), or sulfonylureas. Time zero was defined as the first post-surgical prescription after a 365-day period without use of the study drug class to ensure a new-user design.
Main Outcomes and Measures: Incident KC (renal or renal pelvis; ICD-10 C64, C65, C79.0) after time zero. Propensity score matching (1:1) balanced baseline characteristics. We estimated 19-year risk differences (RDs), risk ratios (RRs), and hazard ratios (HRs).
Results: After matching, 20,662 GLP-1–metformin, 28,358 GLP-1–insulin, 9,745 GLP-1–SGLT2i, and 7,118 GLP-1–sulfonylurea pairs were included. GLP-1 RA initiation was associated with lower KC risk compared with metformin (RD, −0.25%; 95% CI, −0.35% to −0.15%), insulin (RD, −0.31%; 95% CI, −0.39% to −0.23%), SGLT2i (RD, −0.29%; 95% CI, −0.43% to −0.14%), and sulfonylureas (RD, −0.27%; 95% CI, −0.44% to −0.09%). Results were consistent across temporal and diabetes-duration–restricted analyses and were further supported by a negative control outcome.
Conclusions: Among post-MBS patients, GLP-1 RA initiation was associated with a lower risk of KC when compared with several active glucose-lowering drugs. These findings provide insight about reducing the incidence of KC with use of GLP-1 RA after MBS and highlight the need for further investigation among patients with different types of bariatric surgery and more diverse populations.
