The Real-World Clinical Benefits of GLP-1 Receptor Agonist Treatment

Background: The cardiovascular, metabolic and renal benefits of glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been established in randomized trials with carefully selected patients. Real-world evidence of GLP-1RA effects on progression to end-stage renal disease (ESRD), end-stage liver disease (ESLD), and major adverse cardiovascular events (MACE) is scant. Methods: We conducted a large retrospective cohort study of GLP1-RA use in adults using a national medical and pharmacy claims dataset. GLP-1RA users were stratified by diabetes status and propensity score-matched to controls. Outcomes were incident ESRD, ESLD, MACE overall and by treatment persistence (=2 years). Cox models were used to estimate adjusted hazard ratios (HRs) and to calculate confidence intervals (CIs). Results: In members with diabetes, GLP-1RA therapy was associated with reduced risks of ESRD (HR=0.55; 95% CI 0.49 to 0.61), ESLD (HR=0.66; 95% CI 0.60-0.73) and MACE (HR=0.90; 95% CI 0.86-0.93). In members without diabetes, while the incidence rates of adverse outcomes were lower, treatment with GLP-1RAs still resulted in lower risk of ESRD (HR=0.66, CI 0.46-0.94), ESLD (HR=0.76, CI 0.62-0.93) and MACE (HR=0.86, CI 92-0.99). Persistent GLP-1RA treatment (>=2 years) in members with diabetes resulted in the largest observed reduction in ESRD, ESLD, and MACE risk. Conclusions: GLP-1RA treatment was associated with reduced incidence of kidney and liver failure and MACE. The impact of GLP-1RA treatment was greatest in members with diabetes and those persisting for >=2 years.