Comparative Effectiveness of Liraglutide, Semaglutide, and Dulaglutide on Kidney Outcomes

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Background: Although semaglutide is indicated to prevent kidney decline in patients with type 2 diabetes (T2D), it is unknown if this risk is differential between specific glucagon-like peptide-1 receptor agonists. Methods: This active comparator, new user cohort included Veterans Affairs (VA) outpatients (2018-2023) with prevalent T2D treated with metformin who filled outpatient prescriptions for liraglutide, dulaglutide, and semaglutide and had no baseline history of end-stage kidney disease based on diagnosis codes and estimated glomerular filtration rate (eGFR). Cox models, adjusted using inverse probability of treatment weights, estimated hazard ratios for pairwise treatment comparisons with respect to a primary composite outcome of kidney failure, defined as sustained eGFR <15 mL/min/1.73m2 or development of end-stage kidney disease (initiation of dialysis or kidney transplant identified through the VA-linked United States Renal Data System). We secondarily evaluated a cardiovascular-kidney metabolic (CKM) composite outcome of kidney failure and cardiovascular events (stroke/transient ischemic attack, myocardial infarction, heart failure). Patients were followed from treatment initiation to first study outcome, death, or 3/31/2023 (median 3 years). Results: Among 21,790 initiators (25% liraglutide, 50% semaglutide, and 25% dulaglutide; mean age 63 years; 78% Non-Hispanic White), adjusted event rates per 100 person-years were 0.45 (liraglutide), 0.40 (semaglutide), and 0.34 (dulaglutide) for kidney failure and 3.98 (liraglutide), 4.43 (semaglutide), and 3.88 (dulaglutide) for the CKM composite. The adjusted hazard ratios of kidney failure and the CKM composite were similar across all comparisons (Figure). Conclusion: Veterans with T2D initiated on liraglutide, semaglutide, or dulaglutide have similar risks for kidney failure and CKM events. Future head-to-head randomized trials are needed to confirm these findings. Funding: NIDDK Support - NIDDK Support, NIDDK Support, Veterans Affairs Support

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