Glucagon-like Peptide-1 Receptor Agonists and Survival in Advanced Chronic Kidney Disease and Type 2 Diabetes

Background/Objectives: In populations with type 2 diabetes mellitus (T2DM), it is unknown whether the survival benefits of glucagon-like peptide-1 receptor agonists (GLP-1 RA) differ by estimated glomerular filtration rate (eGFR). To address this question and in the absence of definitive randomized controlled trials, we performed a retrospective observational study of US Veterans with T2DM to evaluate mortality hazard ratios associated with GLP-1 RA use at different eGFR levels. Methods: This administrative claims-based cohort included 1,188,052 U.S. Veterans with T2DM as of 1 January 2020. Initiation of GLP-1 RA was treated as a time-dependent variable and vital status of Veterans was followed until 31 December 2023. Results: A total of 31,676 Veterans met inclusion criteria. Over the study timeframe, 6.1% initiated treatment with GLP-1 RA and 57.7% died. Older age and eGFR < 15 mL/min/1.73 m2 were associated with a decreased likelihood of GLP-1 RA initiation. In contrast, younger age and lower comorbidity burden were associated with decreased mortality, a finding that persisted even after adjustment for several baseline covariates. Conclusions: Among those with T2DM and eGFR < 25 mL/min/1.73 m2, initiation of GLP-1 RA was associated with improved survival. This association remained significant with decreasing levels of kidney function, as well as among those receiving kidney replacement therapy (KRT). In conclusion, longer survival was observed both in participants on KRT and in those with eGFR 15–24 mL/min/1.73 m2 not on KRT, but these findings were not observed among those with eGFR ≤ 15 mL/min/1.73 m2.