Semaglutide reduces secondary kidney composite outcome by 8-12% compared to dulaglutide and exenatide in T2D patients

Patients with Type 2 Diabetes (T2D) face a high risk of developing Chronic Kidney Disease (CKD), a serious complication that significantly increases morbidity and mortality. While glucagon-like peptide-1 (GLP-1) receptor agonists are known to lower the risk of incident CKD and death compared to other diabetes medications like DPP-4 inhibitors or sulfonylureas, it has been unclear if specific GLP-1 RAs offer differential kidney protection. Understanding these within-class effects is crucial for optimizing treatment strategies for T2D patients with kidney concerns, especially those at moderate cardiovascular risk.

This retrospective observational study utilized claims data from OptumLabs® Data Warehouse and Medicare fee-for-service. Researchers identified adults aged ≥21 years with Type 2 Diabetes and moderate cardiovascular risk who initiated a new prescription for a GLP-1 receptor agonist between January 1, 2019, and December 31, 2021. The exposures were specific GLP-1 RAs: dulaglutide, exenatide, liraglutide, or semaglutide. The primary endpoint was a kidney composite outcome of incident CKD stages 3-4 and kidney failure. A secondary composite outcome added death from any cause. Inverse probability of treatment weighting (IPTW) with SuperLearner ensemble method was used for propensity score estimation, and cause-specific IPTW Cox proportional hazards models were employed for time-to-event analyses.

The study found no significant difference among dulaglutide, exenatide, liraglutide, and semaglutide regarding the primary kidney composite outcome (incident CKD stages 3-4 and kidney failure). However, when evaluating the secondary kidney composite outcome, which included death from any cause, semaglutide demonstrated superior efficacy compared to two other GLP-1 RAs. Specifically, compared to dulaglutide, semaglutide was associated with an 8% reduced risk for the secondary kidney composite outcome (HR 0.92 [95% CI, 0.87-0.97]). Furthermore, when compared to exenatide, semaglutide was linked to a 12% reduced risk for the secondary kidney composite outcome (HR: 0.88; 95% CI: 0.79-0.99). These findings suggest a differential impact on broader kidney-related outcomes, including mortality, among various GLP-1 receptor agonists. The study did not provide specific comparative data for semaglutide versus liraglutide for the secondary outcome.

Semaglutide significantly reduced the secondary kidney composite outcome by 8% (HR 0.92 [95% CI, 0.87-0.97]) compared to dulaglutide, and by 12% (HR 0.88 [95% CI, 0.79-0.99]) compared to exenatide.