GLP-1 Receptor Agonists, Glomerular Filtration Rates, and Survival in Type 2 Diabetes

Background: It is unknown whether survival benefits from glucagon-like peptide-1 receptor agonists (GLP-1 RA) differ by estimated glomerular filtration rate (eGFR) in populations with type 2 diabetes mellitus (T2DM). In the absence of definitive randomized controlled trials, we performed a national observational study to evaluate mortality hazards ratios associated with GLP-1 RA use at different eGFR levels in subjects with T2DM. Methods: Administrative claims-based study included 1,188,052 subjects with T2DM on January 1st, 2020. Initiation of GLP-1 RA was treated as a time-dependent variable and vital status was followed until was followed until December 31st, 2023. Results: A total of 31,676 subjects were identified for study inclusion. Over the study timeframe, 6.1% initiated treatment with GLP-1 RA and 57.7% died. Older age and GFR < 15 ml/minute/1.73 m2 were associated with decreased initiation of GLP-1 RA. Younger age and less burden of comorbidity was associated with decreased mortality, a finding that persisted even after adjustment for a number of baseline covariates. Conclusion: Initiation of GLP-1 RA was associated with improved survival in those with T2DM and GFR < 25 mL/min/1.73 m2, a finding that remained significant with decreasing levels of kidney function as well as on among those on kidney replacement therapy (KRT). This association with longer survival was present among those on KRT and those not on KRT with GFR between 15 - 24 mL/min/1.73 m2, but not among those with GFR < 15 mL/min/1.73m2.